Immunodeficiency affecting cellular and humoral Immunity: Difference between revisions

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==Overview==
==Overview==
[[Immunodeficiency]] disorders are associated with or predispose patients to various complications, including [[infections]], [[autoimmune disorders]], and [[lymphomas]] and other [[cancers]]. [[Primary immunodeficiencies]] are genetically determined and can be [[hereditary]]; secondary immunodeficiencies are acquired and much more common.  [[combined immune defect]] affecting both types of [[acquired immunity]], i.e. both cellular and humoral responses. [[Acquired immunity]] remembers when it encounters an invading foreign cell or molecule [[antigen]] and quickly mounts a specific response on subsequent encounters. Cellular acquired responses are mediated by [[T cells]], also called [[T lymphocytes]], which kill infected cells, help [[B cells]], and control the immune response. [[Humoral immunity]] is mediated by [[B cells]] which produce antibodies [[immunoglobulins]] that help [[T cells]] and other immune cells to recognize and attack antigens.


==Classification==
==Classification==
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{{Family tree | B01 | | | B02 | | | B03 | | | | B04 | | | B05 | | | B06 | | |B01=Low CD4: MHC II Expression?|B02=Low CD8|B03=Low B Cells|B04=Ig: Often Normal|B05=Ig Low|B06=Normal Ig but Low Specific Antibody Response}}
{{Family tree | B01 | | | B02 | | | B03 | | | | B04 | | | B05 | | | B06 | | |B01=Low CD4: MHC II Expression?|B02=Low CD8|B03=Low B Cells|B04=Ig: Often Normal|B05=Ig Low|B06=Normal Ig but Low Specific Antibody Response}}
{{Family tree |!| | | | |!| | | | |!| | | | | |!| | | | |!| | | | |!| | | | |}}
{{Family tree |!| | | | |!| | | | |!| | | | | |!| | | | |!| | | | |!| | | | |}}
{{Family tree |)| C01 | |)| D01 | |)| E01 | | |)| F01 | |)| G01 | |)| H01 | |C01=Absent: MHCII Deficiency|D01=CD8 def:|E01=DOCK8 def:|F01=CD3Y def:|G01=DOCK2 def:|H01=IL2IR Def:}}
{{Family tree |)| C01 | |)| D01 | |)| E01 | | |)| F01 | |)| G01 | |)| H01 | |C01=Absent: MHCII deficiency|D01=CD8 deficiency|E01=DOCK8 deficiency|F01=CD3Y deficiency|G01=DOCK2 deficiency|H01=IL2IR deficiency}}
{{Family tree |!| | | | |!| | | | |!| | | | | |!| | | | |!| | | | |!| | | | |}}
{{Family tree |!| | | | |!| | | | |!| | | | | |!| | | | |!| | | | |!| | | | |}}
{{Family tree |`| C02 | |)| D02 | |)| E02 | | |)| F02 | |)| G02 | |`| H02 | |C02=Present: MAGT 1 Def:,LCK Def:, UNC119 Def:|D02=ZAP70 def:|E02=MST1 def:|F02=RHOH def:|G02=CARDII def:(LOF)|H02=MALT1 Def: }}
{{Family tree |`| C02 | |)| D02 | |)| E02 | | |)| F02 | |)| G02 | |`| H02 | |C02=Present: MAGT 1 deficiency,LCK deficiency, UNC119 deficiency|D02=ZAP70 deficiency|E02=MST1 deficiency|F02=RHOH deficiency|G02=CARDII deficiency(LOF)|H02=MALT1 deficiency }}
{{Family tree | | | | | |!| | | | |!| | | | | |!| | | | |!| | | | | | | | | |}}
{{Family tree | | | | | |!| | | | |!| | | | | |!| | | | |!| | | | | | | | | |}}
{{Family tree | | | | | |`| D03 | |)| E03 | | |)| F03 | |)| G03 | | | | | | |D03=MHC1 def:|E03=IL21 def:|F03=TCR alpha def:|G03=BCL10 def:|}}
{{Family tree | | | | | |`| D03 | |)| E03 | | |)| F03 | |)| G03 | | | | | | |D03=MHC1 deficiency|E03=IL21 deficiency|F03=TCR alpha deficiency|G03=BCL10 deficiency|}}
{{Family tree | | | | | | | | | | |!| | | | | |!| | | | |!| | | | | | | | | |}}
{{Family tree | | | | | | | | | | |!| | | | | |!| | | | |!| | | | | | | | | |}}
{{Family tree | | | | | | | | | | |)| E04 | | |)| F04 | |)| G04 | | | | | | |E04=NIK def:|F04=BCL11B def:|G04=IKBKB Def:|}}
{{Family tree | | | | | | | | | | |)| E04 | | |)| F04 | |)| G04 | | | | | | |E04=NIK deficiency|F04=BCL11B deficiency|G04=IKBKB deficiency|}}
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{{Family tree | | | | | | | | | | |`| E05 | | |)| F05 | |)| G05 | | | | | | |E05=Moesin def:|F05=OX40 def:|G05=ICOS def:|}}
{{Family tree | | | | | | | | | | |`| E05 | | |)| F05 | |)| G05 | | | | | | |E05=Moesin deficiency|F05=OX40 deficiency|G05=ICOS deficiency|}}
{{Family tree | | | | | | | | | | | | | | | | |!| | | | |!| | | | | | | | | |}}
{{Family tree | | | | | | | | | | | | | | | | |!| | | | |!| | | | | | | | | |}}
{{Family tree | | | | | | | | | | | | | | | | |`| F06 | |)| G06 | | | | | | |F06=LAT def|G06=TFRC def:|}}
{{Family tree | | | | | | | | | | | | | | | | |`| F06 | |)| G06 | | | | | | |F06=LAT deficiency|G06=TFRC deficiency|}}
{{Family tree | | | | | | | | | | | | | | | | | | | | | |!| | | | | | | | | |}}
{{Family tree | | | | | | | | | | | | | | | | | | | | | |!| | | | | | | | | |}}
{{Family tree | | | | | | | | | | | | | | | | | | | | | |)| G07 | | | | | | |G07=RelB def:|}}
{{Family tree | | | | | | | | | | | | | | | | | | | | | |)| G07 | | | | | | |G07=RelB deficiency|}}
{{Family tree | | | | | | | | | | | | | | | | | | | | | |!| | | | | | | | | |}}
{{Family tree | | | | | | | | | | | | | | | | | | | | | |!| | | | | | | | | |}}
{{Family tree | | | | | | | | | | | | | | | | | | | | | |`| G08 | | | | | | |G08=CD40 ligand def:(CD154)  }}
{{Family tree | | | | | | | | | | | | | | | | | | | | | |`| G08 | | | | | | |G08=CD40 ligand deficiency(CD154)  }}
{{Family tree/end}}
{{Family tree/end}}
<br>
<br>
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==γc (IL-2Rγ) deficiency==
==γc (IL-2Rγ) deficiency==
*[[X-linked]] transmission.
*[[X-linked]] transmission.
*It is caused by [[mutation]] in the gene encoding the gamma sub-unit of interleukin-2 receptor ([[IL2RG]]).  
*It is caused by [[mutation]] in the gene encoding the gamma sub-unit of [[interleukin-2]] [[receptor]] ([[IL2RG]]).  
*Patients present with repeated bacterial, viral and fungal [[infections]], lack of delayed hypersensitivity and failure to thrive.<ref>{{Cite journal
*Patients present with repeated [[bacterial]], [[viral]] and fungal [[infections]], lack of delayed [[hypersensitivity]] and failure to thrive.<ref>{{Cite journal
  | author = [[W. H. HITZIG]] & [[H. WILLI]]
  | author = [[W. H. HITZIG]] & [[H. WILLI]]
  | title = &#91;Hereditary lymphoplasmocytic dysgenesis ("alymphocytosis with agammaglobulinemia")&#93;
  | title = &#91;Hereditary lymphoplasmocytic dysgenesis ("alymphocytosis with agammaglobulinemia")&#93;
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==JAK-3 deficiency==
==JAK-3 deficiency==
*[[Autosomal recessive]] (AR) transmission.
*[[Autosomal recessive]] (AR) transmission.
*It is caused by homozygous or compound heterozygous mutation in the [[Janus kinase-3]] gene on [[chromosome 19]].
*It is caused by [[homozygous]] or compound [[heterozygous]] mutation in the [[Janus kinase-3]] gene on [[chromosome 19]].
*It has a similar presentation to X-linked SCID as above.<ref>{{Cite journal
*It has a similar presentation to [[X-linked]] SCID as above.<ref>{{Cite journal
  | author = [[F. Candotti]], [[S. A. Oakes]], [[J. A. Johnston]], [[S. Giliani]], [[R. F. Schumacher]], [[P. Mella]], [[M. Fiorini]], [[A. G. Ugazio]], [[R. Badolato]], [[L. D. Notarangelo]], [[F. Bozzi]], [[P. Macchi]], [[D. Strina]], [[P. Vezzoni]], [[R. M. Blaese]], [[J. J. O'Shea]] & [[A. Villa]]
  | author = [[F. Candotti]], [[S. A. Oakes]], [[J. A. Johnston]], [[S. Giliani]], [[R. F. Schumacher]], [[P. Mella]], [[M. Fiorini]], [[A. G. Ugazio]], [[R. Badolato]], [[L. D. Notarangelo]], [[F. Bozzi]], [[P. Macchi]], [[D. Strina]], [[P. Vezzoni]], [[R. M. Blaese]], [[J. J. O'Shea]] & [[A. Villa]]
  | title = Structural and functional basis for JAK3-deficient severe combined immunodeficiency
  | title = Structural and functional basis for JAK3-deficient severe combined immunodeficiency
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==IL7a==
==IL7a==
*[[Autosomal recessive]] (AR) transmission
*[[Autosomal recessive]] (AR) transmission
*It is caused by homozygous or compound heterozygous mutation in the [[interleukin-7 receptor]] gene on [[chromosome 5]].<ref>{{Cite journal
*It is caused by [[homozygous]] or compound [[heterozygous]] mutation in the [[interleukin-7 receptor]] [[gene]] on [[chromosome 5]].<ref>{{Cite journal
  | author = [[A. Puel]], [[S. F. Ziegler]], [[R. H. Buckley]] & [[W. J. Leonard]]
  | author = [[A. Puel]], [[S. F. Ziegler]], [[R. H. Buckley]] & [[W. J. Leonard]]
  | title = Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency
  | title = Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency
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  | pmid = 9843216
  | pmid = 9843216
}}</ref>
}}</ref>
*It has a similar presentation to X-linked SCID as above<ref>{{Cite journal
*It has a similar presentation to [[X-linked]] [[SCID]] as above<ref>{{Cite journal
  | author = [[C. M. Roifman]], [[J. Zhang]], [[D. Chitayat]] & [[N. Sharfe]]
  | author = [[C. M. Roifman]], [[J. Zhang]], [[D. Chitayat]] & [[N. Sharfe]]
  | title = A partial deficiency of interleukin-7R alpha is sufficient to abrogate T-cell development and cause severe combined immunodeficiency
  | title = A partial deficiency of interleukin-7R alpha is sufficient to abrogate T-cell development and cause severe combined immunodeficiency
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==CD3D==
==CD3D==
*[[Autosomal recessive|Autosomal recessiv]]<nowiki/>e (AR) transmission
*[[Autosomal recessive|Autosomal recessiv]]<nowiki/>e (AR) [[transmission]]
*It is caused by mutation in the delta chain of the T3 T-cell antigen ([[OKT3]]) on [[chromosome 11]].<ref>{{Cite journal
*It is caused by [[mutation]] in the delta chain of the T3 T-cell antigen ([[OKT3]]) on [[chromosome 11]].<ref>{{Cite journal
  | author = [[P. van den Elsen]], [[G. Bruns]], [[D. S. Gerhard]], [[D. Pravtcheva]], [[C. Jones]], [[D. Housman]], [[F. A. Ruddle]], [[S. Orkin]] & [[C. Terhorst]]
  | author = [[P. van den Elsen]], [[G. Bruns]], [[D. S. Gerhard]], [[D. Pravtcheva]], [[C. Jones]], [[D. Housman]], [[F. A. Ruddle]], [[S. Orkin]] & [[C. Terhorst]]
  | title = Assignment of the gene coding for the T3-delta subunit of the T3-T-cell receptor complex to the long arm of human chromosome 11 and to mouse chromosome 9
  | title = Assignment of the gene coding for the T3-delta subunit of the T3-T-cell receptor complex to the long arm of human chromosome 11 and to mouse chromosome 9
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==CD3E==
==CD3E==
*[[Autosomal recessive]] (AR) transmission.
*[[Autosomal recessive]] (AR) transmission.
*It is caused by mutation in the epsilon gene of T3 T-cell antigen on [[chromosome 11]].<ref>{{Cite journal
*It is caused by [[mutation]] in the [[epsilon gene]] of T3 T-cell [[antigen]] on [[chromosome 11]].<ref>{{Cite journal
  | author = [[D. P. Gold]], [[J. J. van Dongen]], [[C. C. Morton]], [[G. A. Bruns]], [[P. van den Elsen]], [[A. H. Geurts van Kessel]] & [[C. Terhorst]]
  | author = [[D. P. Gold]], [[J. J. van Dongen]], [[C. C. Morton]], [[G. A. Bruns]], [[P. van den Elsen]], [[A. H. Geurts van Kessel]] & [[C. Terhorst]]
  | title = The gene encoding the epsilon subunit of the T3/T-cell receptor complex maps to chromosome 11 in humans and to chromosome 9 in mice
  | title = The gene encoding the epsilon subunit of the T3/T-cell receptor complex maps to chromosome 11 in humans and to chromosome 9 in mice
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  | pmid = 2882512
  | pmid = 2882512
}}</ref>
}}</ref>
   
 
==CD247==
==CD247==
*[[Autosomal recessive]] (AR) transmission.
*[[Autosomal recessive]] (AR) transmission.
*It is caused by homozygous mutation in the [[CD247]] (CD3Z) gene on [[chromosome 1]].<ref>{{Cite journal
*It is caused by [[homozygous]] [[mutation]] in the [[CD247]] (CD3Z) gene on [[chromosome 1]].<ref>{{Cite journal
  | author = [[A. M. Weissman]], [[D. Hou]], [[D. G. Orloff]], [[W. S. Modi]], [[H. Seuanez]], [[S. J. O'Brien]] & [[R. D. Klausner]]
  | author = [[A. M. Weissman]], [[D. Hou]], [[D. G. Orloff]], [[W. S. Modi]], [[H. Seuanez]], [[S. J. O'Brien]] & [[R. D. Klausner]]
  | title = Molecular cloning and chromosomal localization of the human T-cell receptor zeta chain: distinction from the molecular CD3 complex
  | title = Molecular cloning and chromosomal localization of the human T-cell receptor zeta chain: distinction from the molecular CD3 complex
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==CD45 deficiency==
==CD45 deficiency==
*[[Autosomal recessive]] (AR) transmission.
*[[Autosomal recessive]] (AR) transmission.
*It is caused by mutation in the [[CD45]] gene on [[chromosome 1]].<ref>{{Cite journal
*It is caused by [[mutation]] in the [[CD45]] [[gene]] on [[chromosome 1]].<ref>{{Cite journal
  | author = [[M. F. Seldin]], [[H. C. Morse]], [[R. C. LeBoeuf]] & [[A. D. Steinberg]]
  | author = [[M. F. Seldin]], [[H. C. Morse]], [[R. C. LeBoeuf]] & [[A. D. Steinberg]]
  | title = Establishment of a molecular genetic map of distal mouse chromosome 1: further definition of a conserved linkage group syntenic with human chromosome 1q
  | title = Establishment of a molecular genetic map of distal mouse chromosome 1: further definition of a conserved linkage group syntenic with human chromosome 1q
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==Coronin-1A deficiency==
==Coronin-1A deficiency==
*[[Autosomal recessive]] (AR) transmission.
*[[Autosomal recessive]] (AR) transmission.
*It is caused by mutation in the [[CORO1A]] gene (which encodes an actin-regulating protein that is expressed mainly in hematopoietic cells) on [[chromosome 16]].<ref>{{Cite journal
*It is caused by [[mutation]] in the [[CORO1A]] [[gene]] (which encodes an actin-regulating protein that is expressed mainly in [[hematopoietic]] cells) on [[chromosome 16]].<ref>{{Cite journal
  | author = [[Lawrence R. Shiow]], [[David W. Roadcap]], [[Kenneth Paris]], [[Susan R. Watson]], [[Irina L. Grigorova]], [[Tonya Lebet]], [[Jinping An]], [[Ying Xu]], [[Craig N. Jenne]], [[Niko Foger]], [[Ricardo U. Sorensen]], [[Christopher C. Goodnow]], [[James E. Bear]], [[Jennifer M. Puck]] & [[Jason G. Cyster]]
  | author = [[Lawrence R. Shiow]], [[David W. Roadcap]], [[Kenneth Paris]], [[Susan R. Watson]], [[Irina L. Grigorova]], [[Tonya Lebet]], [[Jinping An]], [[Ying Xu]], [[Craig N. Jenne]], [[Niko Foger]], [[Ricardo U. Sorensen]], [[Christopher C. Goodnow]], [[James E. Bear]], [[Jennifer M. Puck]] & [[Jason G. Cyster]]
  | title = The actin regulator coronin 1A is mutant in a thymic egress-deficient mouse strain and in a patient with severe combined immunodeficiency
  | title = The actin regulator coronin 1A is mutant in a thymic egress-deficient mouse strain and in a patient with severe combined immunodeficiency
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==Winged helix deficiency/Nude SCID==
==Winged helix deficiency/Nude SCID==
*[[Autosomal recessive]] (AR) transmission.
*[[Autosomal recessive]] (AR) transmission.
*It is caused by a mutation in the [[FOXN1]] gene (a transcription factor essential for the development and function of thymic epithelial cells) on [[chromosome 17]]. <ref>{{Cite journal
*It is caused by a mutation in the [[FOXN1]] [[gene]] (a transcription factor essential for the development and function of thymic epithelial cells) on [[chromosome 17]]. <ref>{{Cite journal
  | author = [[M. Schorpp]], [[M. Hofmann]], [[T. N. Dear]] & [[T. Boehm]]
  | author = [[M. Schorpp]], [[M. Hofmann]], [[T. N. Dear]] & [[T. Boehm]]
  | title = Characterization of mouse and human nude genes
  | title = Characterization of mouse and human nude genes
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  | pmid = 27548434
  | pmid = 27548434
}}</ref>
}}</ref>
*Patients usually have the clinical triad of athymia, congenital [[alopecia universalis]] and nail [[dystrophy]] and present in early few months of life with severe, recurrent [[infections]].<ref>{{Cite journal
*Patients usually have the clinical triad of athymia, [[congenital]] [[alopecia universalis]] and nail [[dystrophy]] and present in early few months of life with severe, recurrent [[infections]].<ref>{{Cite journal
  | author = [[C. Pignata]], [[M. Fiore]], [[V. Guzzetta]], [[A. Castaldo]], [[G. Sebastio]], [[F. Porta]] & [[A. Guarino]]
  | author = [[C. Pignata]], [[M. Fiore]], [[V. Guzzetta]], [[A. Castaldo]], [[G. Sebastio]], [[F. Porta]] & [[A. Guarino]]
  | title = Congenital Alopecia and nail dystrophy associated with severe functional T-cell immunodeficiency in two sibs
  | title = Congenital Alopecia and nail dystrophy associated with severe functional T-cell immunodeficiency in two sibs
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  | pmid = 25564533
  | pmid = 25564533
}}</ref>     
}}</ref>     
*Prophylaxis and early treatment of infections is also an important step in management.<ref>{{Cite journal
*[[Prophylaxis]] and early treatment of [[infections]] is also an important step in [[management]].<ref>{{Cite journal
  | author = [[Linda M. Griffith]], [[Morton J. Cowan]], [[Luigi D. Notarangelo]], [[Jennifer M. Puck]], [[Rebecca H. Buckley]], [[Fabio Candotti]], [[Mary Ellen Conley]], [[Thomas A. Fleisher]], [[H. Bobby Gaspar]], [[Donald B. Kohn]], [[Hans D. Ochs]], [[Richard J. O'Reilly]], [[J. Douglas Rizzo]], [[Chaim M. Roifman]], [[Trudy N. Small]] & [[William T. Shearer]]
  | author = [[Linda M. Griffith]], [[Morton J. Cowan]], [[Luigi D. Notarangelo]], [[Jennifer M. Puck]], [[Rebecca H. Buckley]], [[Fabio Candotti]], [[Mary Ellen Conley]], [[Thomas A. Fleisher]], [[H. Bobby Gaspar]], [[Donald B. Kohn]], [[Hans D. Ochs]], [[Richard J. O'Reilly]], [[J. Douglas Rizzo]], [[Chaim M. Roifman]], [[Trudy N. Small]] & [[William T. Shearer]]
  | title = Improving cellular therapy for primary immune deficiency diseases: recognition, diagnosis, and management
  | title = Improving cellular therapy for primary immune deficiency diseases: recognition, diagnosis, and management
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==ADA deficiency==
==ADA deficiency==
*[[Autosomal recessive]] (AR) transmission.
*[[Autosomal recessive]] (AR) transmission.
*It is caused by homozygous or compound heterozygous mutation in the [[adenosine deaminase]] gene (ADA) on [[Chromosome 20 (human)|chromosome 20]].
*It is caused by [[homozygous]] or compound [[heterozygous]] [[mutation]] in the [[adenosine deaminase]] [[gene]] (ADA) on [[Chromosome 20 (human)|chromosome 20]].
*Patients have chondrosternal dysplasia, neurologic abnormalities like movement disorders, [[nystagmus]], [[sensorineural deafness]] and cognitive defects, and also hepatic dysfucnction.<ref>{{Cite journal
*Patients have [[chondrosternal dysplasia]], neurologic abnormalities like movement disorders, [[nystagmus]], [[sensorineural deafness]] and [[cognitive defects]], and also [[hepatic dysfucnction]].<ref>{{Cite journal
  | author = [[H. Ratech]], [[M. A. Greco]], [[G. Gallo]], [[D. L. Rimoin]], [[H. Kamino]] & [[R. Hirschhorn]]
  | author = [[H. Ratech]], [[M. A. Greco]], [[G. Gallo]], [[D. L. Rimoin]], [[H. Kamino]] & [[R. Hirschhorn]]
  | title = Pathologic findings in adenosine deaminase-deficient severe combined immunodeficiency. I. Kidney, adrenal, and chondro-osseous tissue alterations
  | title = Pathologic findings in adenosine deaminase-deficient severe combined immunodeficiency. I. Kidney, adrenal, and chondro-osseous tissue alterations
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}}</ref>
}}</ref>
*Treatment options include:
*Treatment options include:
*#Enzyme replacement therapy: Pegademase bovine (PEG-ADA) is used as the replacement therapy.<ref>{{Cite journal
*#Enzyme replacement therapy: [[Pegademase bovine]] (PEG-ADA) is used as the [[replacement therapy]].<ref>{{Cite journal
  | author = [[M. S. Hershfield]]
  | author = [[M. S. Hershfield]]
  | title = PEG-ADA: an alternative to haploidentical bone marrow transplantation and an adjunct to gene therapy for adenosine deaminase deficiency
  | title = PEG-ADA: an alternative to haploidentical [[bone marrow transplantation]] and an adjunct to gene therapy for [[adenosine deaminase]] deficiency
  | journal = [[Human mutation]]
  | journal = [[Human mutation]]
  | volume = 5
  | volume = 5
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==Reticular dysgenesis==
==Reticular dysgenesis==
*[[Autosomal recessive]] (AR) transmission.
*[[Autosomal recessive]] (AR) transmission.
*It is caused by homozygous or compound heterozygous mutation in the mitochondrial adenylate kinase-2 gene ([[AK2]]) on [[chromosome 1]].
*It is caused by [[homozygous]] or compound [[heterozygous]] [[mutation]] in the [[mitochondrial adenylate kinase-2 gene]] ([[AK2]]) on [[chromosome 1]].
*Patients present with [[agranulocytosis]], [[lymphopenia]] and [[sensorineural hearing loss]].
*Patients present with [[agranulocytosis]], [[lymphopenia]] and [[sensorineural hearing loss]].
*[[Bone marrow transplant]] is the treatment of choice.<ref>{{Cite journal
*[[Bone marrow transplant]] is the treatment of choice.<ref>{{Cite journal
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==DNA Ligase IV deficiency==
==DNA Ligase IV deficiency==
*[[Autosomal recessive]] (AR) transmission.
*[[Autosomal recessive]] (AR) transmission.
*It is caused by homozygous or compound heterozygous mutation in the [[LIG4]] gene on [[chromosome 13]].
*It is caused by [[homozygous]] or compound [[heterozygous]] [[mutation]] in the [[LIG4]] gene on [[chromosome 13]].
*Patients show unusual facial features, [[microcephaly]], [[developmental delay]], [[Pancytopenia|pancytopenia,]] and various skin abnormalities.<ref>{{Cite journal
*Patients show unusual facial features, [[microcephaly]], [[developmental delay]], [[Pancytopenia|pancytopenia,]] and various skin abnormalities.<ref>{{Cite journal
  | author = [[M. O'Driscoll]], [[K. M. Cerosaletti]], [[P. M. Girard]], [[Y. Dai]], [[M. Stumm]], [[B. Kysela]], [[B. Hirsch]], [[A. Gennery]], [[S. E. Palmer]], [[J. Seidel]], [[R. A. Gatti]], [[R. Varon]], [[M. A. Oettinger]], [[H. Neitzel]], [[P. A. Jeggo]] & [[P. Concannon]]
  | author = [[M. O'Driscoll]], [[K. M. Cerosaletti]], [[P. M. Girard]], [[Y. Dai]], [[M. Stumm]], [[B. Kysela]], [[B. Hirsch]], [[A. Gennery]], [[S. E. Palmer]], [[J. Seidel]], [[R. A. Gatti]], [[R. Varon]], [[M. A. Oettinger]], [[H. Neitzel]], [[P. A. Jeggo]] & [[P. Concannon]]
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  | pmid = 11779494
  | pmid = 11779494
}}</ref>
}}</ref>
   
 
==CERNUNNOS/XLF deficiency==
==CERNUNNOS/XLF deficiency==
*[[Autosomal recessive]] (AR) transmission.
*[[Autosomal recessive]] (AR) transmission.
*It is caused by mutations in the [[NHEJ1]] gene on [[chromosome 2]].  
*It is caused by [[mutations]] in the [[NHEJ1]] [[gene]] on [[chromosome 2]].  
*It is characterized by [[microcephaly]], [[growth retardation]] and sensitivity to ionizing radiation.<ref>{{Cite journal
*It is characterized by [[microcephaly]], [[growth retardation]] and [[sensitivity]] to [[ionizing radiation]].<ref>{{Cite journal
  | author = [[Dietke Buck]], [[Laurent Malivert]], [[Regina de Chasseval]], [[Anne Barraud]], [[Marie-Claude Fondaneche]], [[Ozden Sanal]], [[Alessandro Plebani]], [[Jean-Louis Stephan]], [[Markus Hufnagel]], [[Francoise le Deist]], [[Alain Fischer]], [[Anne Durandy]], [[Jean-Pierre de Villartay]] & [[Patrick Revy]]
  | author = [[Dietke Buck]], [[Laurent Malivert]], [[Regina de Chasseval]], [[Anne Barraud]], [[Marie-Claude Fondaneche]], [[Ozden Sanal]], [[Alessandro Plebani]], [[Jean-Louis Stephan]], [[Markus Hufnagel]], [[Francoise le Deist]], [[Alain Fischer]], [[Anne Durandy]], [[Jean-Pierre de Villartay]] & [[Patrick Revy]]
  | title = Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly
  | title = Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly
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==DNA PKcs deficiency==
==DNA PKcs deficiency==
*[[Autosomal recessive]] (AR) transmission.
*[[Autosomal recessive]] (AR) transmission.
*It is caused by a mutation in the PRKDC gene on [[chromosome 8]].<ref>{{Cite journal
*It is caused by a [[mutation]] in the [[PRKDC gene]] on [[chromosome 8]].<ref>{{Cite journal
  | author = [[J. D. Sipley]], [[J. C. Menninger]], [[K. O. Hartley]], [[D. C. Ward]], [[S. P. Jackson]] & [[C. W. Anderson]]
  | author = [[J. D. Sipley]], [[J. C. Menninger]], [[K. O. Hartley]], [[D. C. Ward]], [[S. P. Jackson]] & [[C. W. Anderson]]
  | title = Gene for the catalytic subunit of the human DNA-activated protein kinase maps to the site of the XRCC7 gene on chromosome 8
  | title = Gene for the catalytic subunit of the human DNA-activated protein kinase maps to the site of the XRCC7 gene on chromosome 8
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==RAG 1/2 deficiency==
==RAG 1/2 deficiency==
*[[Autosomal recessive]] (AR) transmission.     
*[[Autosomal recessive]] (AR) transmission.     
*It is caused by homozygous or compound heterozygous mutations in the [[RAG1]] and [[RAG2]] genes on [[chromosome 11]].<ref>{{Cite journal
*It is caused by [[homozygous]] or compound [[heterozygous]] [[mutations]] in the [[RAG1]] and [[RAG2]] [[genes]] on [[chromosome 11]].<ref>{{Cite journal
  | author = [[K. Schwarz]], [[G. H. Gauss]], [[L. Ludwig]], [[U. Pannicke]], [[Z. Li]], [[D. Lindner]], [[W. Friedrich]], [[R. A. Seger]], [[T. E. Hansen-Hagge]], [[S. Desiderio]], [[M. R. Lieber]] & [[C. R. Bartram]]
  | author = [[K. Schwarz]], [[G. H. Gauss]], [[L. Ludwig]], [[U. Pannicke]], [[Z. Li]], [[D. Lindner]], [[W. Friedrich]], [[R. A. Seger]], [[T. E. Hansen-Hagge]], [[S. Desiderio]], [[M. R. Lieber]] & [[C. R. Bartram]]
  | title = RAG mutations in human B cell-negative SCID
  | title = RAG mutations in human B cell-negative SCID
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  | pmid = 8810255
  | pmid = 8810255
}}</ref>
}}</ref>
*Patients present with persistent [[diarrhea]], [[candidiasis]], lung infections, [[fever]], and opportunistic infections.<ref>{{Cite journal
*Patients present with persistent [[diarrhea]], [[candidiasis]], [[lung infections]], [[fever]], and [[opportunistic infections]].<ref>{{Cite journal
  | author = [[J. L. Stephan]], [[V. Vlekova]], [[F. Le Deist]], [[S. Blanche]], [[J. Donadieu]], [[G. De Saint-Basile]], [[A. Durandy]], [[C. Griscelli]] & [[A. Fischer]]
  | author = [[J. L. Stephan]], [[V. Vlekova]], [[F. Le Deist]], [[S. Blanche]], [[J. Donadieu]], [[G. De Saint-Basile]], [[A. Durandy]], [[C. Griscelli]] & [[A. Fischer]]
  | title = Severe combined immunodeficiency: a retrospective single-center study of clinical presentation and outcome in 117 patients
  | title = Severe combined immunodeficiency: a retrospective single-center study of clinical presentation and outcome in 117 patients
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==DCLRE1C deficiency==
==DCLRE1C deficiency==
*[[Autosomal recessive]] (AR) transmission.   
*[[Autosomal recessive]] (AR) transmission.   
*It is caused by mutation in the gene encoding [[Artemis (protein)|Artemis]] in [[chromosome 10]].<ref>{{Cite journal
*It is caused by [[mutation]] in the [[gene]] encoding [[Artemis (protein)|Artemis]] in [[chromosome 10]].<ref>{{Cite journal
  | author = [[L. Li]], [[D. Drayna]], [[D. Hu]], [[A. Hayward]], [[S. Gahagan]], [[H. Pabst]] & [[M. J. Cowan]]
  | author = [[L. Li]], [[D. Drayna]], [[D. Hu]], [[A. Hayward]], [[S. Gahagan]], [[H. Pabst]] & [[M. J. Cowan]]
  | title = The gene for severe combined immunodeficiency disease in Athabascan-speaking Native Americans is located on chromosome 10p
  | title = The gene for severe combined immunodeficiency disease in Athabascan-speaking Native Americans is located on chromosome 10p
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==Combined Immunodeficiencies Generally Less Pronounced than Severe Combined Immunodeficiency==
==Combined Immunodeficiencies Generally Less Pronounced than Severe Combined Immunodeficiency==


==MHC II Deficiency==
==Major Histocompatibility Complex II Deficiency==
*MHC class II deficiency, called as the bare lymphocyte syndrome type II.
 
*a rare autosomal recessive disorder.
* Major Histocompatibility Complex class II deficiency, called as the [[bare lymphocyte syndrome]] type II.<ref name="pmid8717517">{{cite journal |vauthors=Mach B, Steimle V, Martinez-Soria E, Reith W |title=Regulation of MHC class II genes: lessons from a disease |journal=Annu. Rev. Immunol. |volume=14 |issue= |pages=301–31 |date=1996 |pmid=8717517 |doi=10.1146/annurev.immunol.14.1.301 |url=}}</ref>
*Lack of constitutive and inducible MHC class II expression in all cell types and tissues.<ref name="pmid8717517">{{cite journal |vauthors=Mach B, Steimle V, Martinez-Soria E, Reith W |title=Regulation of MHC class II genes: lessons from a disease |journal=Annu. Rev. Immunol. |volume=14 |issue= |pages=301–31 |date=1996 |pmid=8717517 |doi=10.1146/annurev.immunol.14.1.301 |url=}}</ref>
* It is a rare [[autosomal recessive]] disorder.
* Lack of constitutive and inducible [[MHC class II]] expression in all cell types and tissues.
 
==Magnesium Transporter Gene (MAGT1) Deficiency, Lymphocyte-Specific Protein Tyrosine Kinase (LCK) Deficiency, UNC119 Deficiency==
 
*[[Magnesium transporter gene]] (MAGT1) deficiency, [[T-cell]] [[tyrosine kinase]] Lck deficiency and [[Signaling adaptor protein Uncoordinated 119]] (Unc119) deficiency related with a condition called [[Idiopathic]] [[CD4]] [[lymphopenia]]. <ref name="pmid22184408">{{cite journal |vauthors=Gorska MM, Alam R |title=A mutation in the human Uncoordinated 119 gene impairs TCR signaling and is associated with CD4 lymphopenia |journal=Blood |volume=119 |issue=6 |pages=1399–406 |date=February 2012 |pmid=22184408 |pmc=3286207 |doi=10.1182/blood-2011-04-350686 |url=}}</ref>
*MAGT1 deficiency stops the Mg (2+) influx, which impairs responses to [[antigen]] receptor engagement and successive steps like activation of [[phospholipase]] Cγ1 and Ca(2+) influx in [[T cells]] but not [[B cells]].<ref name="pmid21796205">{{cite journal |vauthors=Li FY, Chaigne-Delalande B, Kanellopoulou C, Davis JC, Matthews HF, Douek DC, Cohen JI, Uzel G, Su HC, Lenardo MJ |title=Second messenger role for Mg2+ revealed by human T-cell immunodeficiency |journal=Nature |volume=475 |issue=7357 |pages=471–6 |date=July 2011 |pmid=21796205 |pmc=3159560 |doi=10.1038/nature10246 |url=}}</ref>
*Lck is vital for both [[CD4]] and [[CD8]] [[T-cell]] development and function. LCK deficiency decrease [[T cell]] proliferation.<ref name="pmid10744646">{{cite journal |vauthors=Hubert P, Bergeron F, Ferreira V, Seligmann M, Oksenhendler E, Debre P, Autran B |title=Defective p56Lck activity in T cells from an adult patient with idiopathic CD4+ lymphocytopenia |journal=Int. Immunol. |volume=12 |issue=4 |pages=449–57 |date=April 2000 |pmid=10744646 |doi= |url=}}</ref>
*Unc119 is necessary for activation of [[T-cell]] [[tyrosine kinase]] Lck. Unc119-deficiency reduce the activity of LCK and decrease [[interleukin 2]] production and cellular proliferation.<ref name="pmid16966372">{{cite journal |vauthors=Lovatt M, Filby A, Parravicini V, Werlen G, Palmer E, Zamoyska R |title=Lck regulates the threshold of activation in primary T cells, while both Lck and Fyn contribute to the magnitude of the extracellular signal-related kinase response |journal=Mol. Cell. Biol. |volume=26 |issue=22 |pages=8655–65 |date=November 2006 |pmid=16966372 |pmc=1636771 |doi=10.1128/MCB.00168-06 |url=}}</ref>
 
==CD8 Deficiency==
*[[CD8]] [[glycoproteins]] play vital role in both the maturation and function of MHC class I-restricted T lymphocytes.<ref name="pmid11435463">{{cite journal |vauthors=de la Calle-Martin O, Hernandez M, Ordi J, Casamitjana N, Arostegui JI, Caragol I, Ferrando M, Labrador M, Rodriguez-Sanchez JL, Espanol T |title=Familial CD8 deficiency due to a mutation in the CD8 alpha gene |journal=J. Clin. Invest. |volume=108 |issue=1 |pages=117–23 |date=July 2001 |pmid=11435463 |pmc=209336 |doi=10.1172/JCI10993 |url=}}</ref>
 
*CD8 deficiency is [[autosomal recessive]] familial condition.
*There is single mutation in the CD8α gene that is due to missense mutation (gly90-->ser) in both alleles of the [[immunoglobulin]] domain of the CD8 alpha gene.
 
==Zeta-Chain-Associated Protein Kinase 70 (ZAP70) Deficiency==
*[[ZAP70]] [[gene]] encodes a [[tyrosine kinase]] that is important for [[T-cell signaling]].<ref name="pmid8124727">{{cite journal |vauthors=Arpaia E, Shahar M, Dadi H, Cohen A, Roifman CM |title=Defective T cell receptor signaling and CD8+ thymic selection in humans lacking zap-70 kinase |journal=Cell |volume=76 |issue=5 |pages=947–58 |date=March 1994 |pmid=8124727 |doi= |url=}}</ref>
*[[ZAP70]] deficiency, results in loss of the activity of this [[kinase]].
*[[ZAP70]] is expressed mostly in T and [[NK cells]], deficiency causes dysregulated [[T cells]].<ref name="pmid26783323">{{cite journal |vauthors=Chan AY, Punwani D, Kadlecek TA, Cowan MJ, Olson JL, Mathes EF, Sunderam U, Fu SM, Srinivasan R, Kuriyan J, Brenner SE, Weiss A, Puck JM |title=A novel human autoimmune syndrome caused by combined hypomorphic and activating mutations in ZAP-70 |journal=J. Exp. Med. |volume=213 |issue=2 |pages=155–65 |date=February 2016 |pmid=26783323 |pmc=4749924 |doi=10.1084/jem.20150888 |url=}}</ref>
 
==Major Histocompatibility Complex 1 Deficiency==
*It is [[autosomal recessive]] disorder also called as [[Bare lymphocyte syndrome]] type I.<ref name="pmid25001848">{{cite journal |vauthors=Hanna S, Etzioni A |title=MHC class I and II deficiencies |journal=J. Allergy Clin. Immunol. |volume=134 |issue=2 |pages=269–75 |date=August 2014 |pmid=25001848 |doi=10.1016/j.jaci.2014.06.001 |url=}}</ref>
*It is extremely rare condition, less than 30 patients reported worldwide.
*There is [[homozygous]] inactivating mutation of [[transporter associated with antigen processing]] (TAP), which helps in [[peptide]] loading on [[MHC1]].<ref name="pmid16087697">{{cite journal |vauthors=Zimmer J, Andrès E, Donato L, Hanau D, Hentges F, de la Salle H |title=Clinical and immunological aspects of HLA class I deficiency |journal=QJM |volume=98 |issue=10 |pages=719–27 |date=October 2005 |pmid=16087697 |doi=10.1093/qjmed/hci112 |url=}}</ref>
 
==Dedicator of Cytokinesis 8 (DOCK8) Deficiency==
* It is previously known as [[autosomal recessive]] [[hyper-IgE syndrome]].<ref name="pmid20864884">{{cite journal |vauthors=Su HC |title=Dedicator of cytokinesis 8 (DOCK8) deficiency |journal=Curr Opin Allergy Clin Immunol |volume=10 |issue=6 |pages=515–20 |date=December 2010 |pmid=20864884 |pmc=3096565 |doi=10.1097/ACI.0b013e32833fd718 |url=}}</ref>
*Absence of [[DOCK8]] expression impairs [[T cell]] expansion, which causes [[T cell]] [[lymphopenia]] and susceptibility to cutaneous viral infections.
*Clinical manifestation includes [[eczema]], recurrent [[skin abscesses]], [[pneumonias]], and elevated [[serum]] [[IgE]].
 
==Macrophage Stimulating 1 Deficiency==
* Macrophage stimulating 1 encoded by [[gene]] contains four kringle domains and a [[serine protease]] domain.<ref name="urlMST1 macrophage stimulating 1 [Homo sapiens (human)] - Gene - NCBI">{{cite web |url=https://www.ncbi.nlm.nih.gov/gene/4485#reference-sequences |title=MST1 macrophage stimulating 1 [Homo sapiens (human)] - Gene - NCBI |format= |work= |accessdate=}}</ref>
* Macrophage Stimulating 1 (MST1) deficiency causes increased [[cell death]] of naive and proliferating T cells.<ref name="pmid22174160">{{cite journal |vauthors=Nehme NT, Schmid JP, Debeurme F, André-Schmutz I, Lim A, Nitschke P, Rieux-Laucat F, Lutz P, Picard C, Mahlaoui N, Fischer A, de Saint Basile G |title=MST1 mutations in autosomal recessive primary immunodeficiency characterized by defective naive T-cell survival |journal=Blood |volume=119 |issue=15 |pages=3458–68 |date=April 2012 |pmid=22174160 |pmc=3824282 |doi=10.1182/blood-2011-09-378364 |url=}}</ref>
*MST1-deficient [[T cells]] poorly expressed the [[transcription factor]] [[FOXO1]], the [[IL-7 receptor]], and [[BCL2]].
 
==Interleukin 21 Deficiency==
 
*[[IL-21]] is produced by activated [[T cells]].<ref name="pmid17509926">{{cite journal |vauthors=Brandt K, Singh PB, Bulfone-Paus S, Rückert R |title=Interleukin-21: a new modulator of immunity, infection, and cancer |journal=Cytokine Growth Factor Rev. |volume=18 |issue=3-4 |pages=223–32 |date=2007 |pmid=17509926 |doi=10.1016/j.cytogfr.2007.04.003 |url=}}</ref>
*[[IL-21]] targets [[lymphoid]] and [[myeloid]] cells and regulates [[innate and acquired immune]] responses.
*[[Homozygous]] [[loss-of-function mutations]] in the [[interleukin-21]] receptor [[gene]] is one cause of [[IL21]] deficiency.<ref name="pmid23440042">{{cite journal |vauthors=Kotlarz D, Ziętara N, Uzel G, Weidemann T, Braun CJ, Diestelhorst J, Krawitz PM, Robinson PN, Hecht J, Puchałka J, Gertz EM, Schäffer AA, Lawrence MG, Kardava L, Pfeifer D, Baumann U, Pfister ED, Hanson EP, Schambach A, Jacobs R, Kreipe H, Moir S, Milner JD, Schwille P, Mundlos S, Klein C |title=Loss-of-function mutations in the IL-21 receptor gene cause a primary immunodeficiency syndrome |journal=J. Exp. Med. |volume=210 |issue=3 |pages=433–43 |date=March 2013 |pmid=23440042 |pmc=3600901 |doi=10.1084/jem.20111229 |url=}}</ref>
 
*[[IL-21]] deficiency causes impaired proliferation and [[immunoglobulin]] class-switching in [[B cells]].
 
== NF-κB inducing kinase Deficiency==
 
*[[NF-κB-inducing kinase]] (NIK) is involved in [[lymphoid]] organogenesis through [[lymphotoxin]]-β receptor signaling.<ref name="urlEssential Role of NF-κB-Inducing Kinase in T Cell Activation Through the TCR/CD3 Pathway | The Journal of Immunology">{{cite web |url=+https://doi.org/10.4049/jimmunol.169.3.1151 |title=Essential Role of NF-κB-Inducing Kinase in T Cell Activation Through the TCR/CD3 Pathway &#124; The Journal of Immunology |format= |work= |accessdate=}}</ref>
*NIK deficiency is [[autosomal recessive]] disorder.<ref>Rezaei, Nima, Asghar Aghamohammadi, and Luigi Notarangelo. Primary immunodeficiency diseases : definition, diagnosis, and management. Berlin, Germany: Springer, 2016. Print </ref>
 
*It is caused by mutation in [[MAP3K14]].
 
==Moesin Deficiency==
* It is newly described [[X linked]] combined [[immunodeficiency]].<ref name="pmid28378256">{{cite journal |vauthors=Delmonte OM, Biggs CM, Hayward A, Comeau AM, Kuehn HS, Rosenzweig SD, Notarangelo LD |title=First Case of X-Linked Moesin Deficiency Identified After Newborn Screening for SCID |journal=J. Clin. Immunol. |volume=37 |issue=4 |pages=336–338 |date=May 2017 |pmid=28378256 |pmc=6082367 |doi=10.1007/s10875-017-0391-9 |url=}}</ref>
 
* It present early in life with [[lymphopenia]] and [[hypogammaglobulinemia]].
* There is poor [[immune]] response to [[vaccine]] antigens, and increased susceptibility to [[bacterial]] and [[[varicella zoster virus]] (VZV) infections.
* This [[immunodeficiency]] is caused by [[genetic defects]] of the [[moesin]] (MSN) [[gene]].
 
==CD3Y Deficiency==
 
*Deficiency of the CD3Y component of the TcR/CD3 complex is associated with a long-term severe defect of peripheral blood CD4+ CD45RA+ and CD8+ lymphocytes, whereas CD4+CD45RO+, B and natural killer lymphocytes are unaffected.<ref name="pmid8325321">{{cite journal |vauthors=Timón M, Arnaiz-Villena A, Rodríguez-Gallego C, Pérez-Aciego P, Pacheco A, Regueiro JR |title=Selective disbalances of peripheral blood T lymphocyte subsets in human CD3 gamma deficiency |journal=Eur. J. Immunol. |volume=23 |issue=7 |pages=1440–4 |date=July 1993 |pmid=8325321 |doi=10.1002/eji.1830230706 |url=}}</ref>
*These results suggest that the CD3Y site of the TcR/CD3 complex is required for the peripheral representation of certain T cell types.
 
==RHOH Deficiency==
 
* Ras homolog gene family H (RhoH) is a membrane-bound adaptor protein that helps in proximal [[T-cell]] receptor signaling.<ref name="urlRedirecting">{{cite web |url=https://doi.org/10.1016/j.jaci.2018.09.032 |title=Redirecting |format= |work= |accessdate=}}</ref>
* Ras homolog gene family H (RHOH) deficiency leads to T cell defects and persistent [[HPV]] infections.<ref name="pmid22850876">{{cite journal |vauthors=Crequer A, Troeger A, Patin E, Ma CS, Picard C, Pedergnana V, Fieschi C, Lim A, Abhyankar A, Gineau L, Mueller-Fleckenstein I, Schmidt M, Taieb A, Krueger J, Abel L, Tangye SG, Orth G, Williams DA, Casanova JL, Jouanguy E |title=Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV infections |journal=J. Clin. Invest. |volume=122 |issue=9 |pages=3239–47 |date=September 2012 |pmid=22850876 |pmc=3428089 |doi=10.1172/JCI62949 |url=}}</ref>
* RHOH encodes an atypical Rho GTPase expressed predominantly in [[hematopoietic]] cells.
 
==T-cell Receptor Alpha Deficiency==
 
* The alpha chain is synthesized by recombination joining of single V segment with a J segment.  Recombination of many different V segments with several J segments provides a wide range of antigen recognition.<ref name="urlTcra T cell receptor alpha chain [Mus musculus (house mouse)] - Gene - NCBI">{{cite web |url=https://www.ncbi.nlm.nih.gov/gene/21473 |title=Tcra T cell receptor alpha chain [Mus musculus (house mouse)] - Gene - NCBI |format= |work= |accessdate=}}</ref>
* [[T-cell]] receptor-alpha deficiency is [[autosomal recessive]] disorder.<ref name="pmid21206088">{{cite journal |vauthors=Morgan NV, Goddard S, Cardno TS, McDonald D, Rahman F, Barge D, Ciupek A, Straatman-Iwanowska A, Pasha S, Guckian M, Anderson G, Huissoon A, Cant A, Tate WP, Hambleton S, Maher ER |title=Mutation in the TCRα subunit constant gene (TRAC) leads to a human immunodeficiency disorder characterized by a lack of TCRαβ+ T cells |journal=J. Clin. Invest. |volume=121 |issue=2 |pages=695–702 |date=February 2011 |pmid=21206088 |pmc=3026716 |doi=10.1172/JCI41931 |url=}}</ref>
* It is caused by homozygous mutation in the TRAC gene on [[chromosome]] 14q11.
 
==BCL11B Deficiency==
 
* BCL11B is required for [[T-cell]] differentiation and have vital role in the transcriptional regulation of these genes.<ref name="pmid20544728">{{cite journal |vauthors=Kastner P, Chan S, Vogel WK, Zhang LJ, Topark-Ngarm A, Golonzhka O, Jost B, Le Gras S, Gross MK, Leid M |title=Bcl11b represses a mature T-cell gene expression program in immature CD4(+)CD8(+) thymocytes |journal=Eur. J. Immunol. |volume=40 |issue=8 |pages=2143–54 |date=August 2010 |pmid=20544728 |pmc=2942964 |doi=10.1002/eji.200940258 |url=}}</ref>
* BCL11B gene encodes a zinc-finger transcription factor involved in [[hematopoietic]] progenitor cell development.<ref name="pmid27959755">{{cite journal |vauthors=Punwani D, Zhang Y, Yu J, Cowan MJ, Rana S, Kwan A, Adhikari AN, Lizama CO, Mendelsohn BA, Fahl SP, Chellappan A, Srinivasan R, Brenner SE, Wiest DL, Puck JM |title=Multisystem Anomalies in Severe Combined Immunodeficiency with Mutant BCL11B |journal=N. Engl. J. Med. |volume=375 |issue=22 |pages=2165–2176 |date=December 2016 |pmid=27959755 |pmc=5215776 |doi=10.1056/NEJMoa1509164 |url=}}</ref>
* Bcl11b deficiency results in structural brain defects, reduced learning capacity, and impaired [[immune cell]] development.<ref name="pmid29985992">{{cite journal |vauthors=Lessel D, Gehbauer C, Bramswig NC, Schluth-Bolard C, Venkataramanappa S, van Gassen KLI, Hempel M, Haack TB, Baresic A, Genetti CA, Funari MFA, Lessel I, Kuhlmann L, Simon R, Liu P, Denecke J, Kuechler A, de Kruijff I, Shoukier M, Lek M, Mullen T, Lüdecke HJ, Lerario AM, Kobbe R, Krieger T, Demeer B, Lebrun M, Keren B, Nava C, Buratti J, Afenjar A, Shinawi M, Guillen Sacoto MJ, Gauthier J, Hamdan FF, Laberge AM, Campeau PM, Louie RJ, Cathey SS, Prinz I, Jorge AAL, Terhal PA, Lenhard B, Wieczorek D, Strom TM, Agrawal PB, Britsch S, Tolosa E, Kubisch C |title=BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells |journal=Brain |volume= |issue= |pages= |date=July 2018 |pmid=29985992 |doi=10.1093/brain/awy173 |url=}}</ref>
 
==OX40 Deficiency==
 
* It is an [[autosomal recessive]] disorder. <ref name="pmid23897980">{{cite journal |vauthors=Byun M, Ma CS, Akçay A, Pedergnana V, Palendira U, Myoung J, Avery DT, Liu Y, Abhyankar A, Lorenzo L, Schmidt M, Lim HK, Cassar O, Migaud M, Rozenberg F, Canpolat N, Aydogan G, Fleckenstein B, Bustamante J, Picard C, Gessain A, Jouanguy E, Cesarman E, Olivier M, Gros P, Abel L, Croft M, Tangye SG, Casanova JL |title=Inherited human OX40 deficiency underlying classic Kaposi sarcoma of childhood |journal=J. Exp. Med. |volume=210 |issue=9 |pages=1743–59 |date=August 2013 |pmid=23897980 |pmc=3754857 |doi=10.1084/jem.20130592 |url=}}</ref>
* OX40 is a co-stimulatory receptor expressed on activated [[T cells]].
* Its ligand, OX40L, is expressed on various cell types, including [[endothelial cells]].
* OX40L was abundantly expressed in [[Kaposi Sarcoma]] lesions.
* OX40 deficiency causes low proportion of effector memory CD4(+) T cells in the peripheral [[blood]].
 
==LAT Deficiency==
 
* Linker for Activation of T cell (LAT) is substrate of the ZAP70 [[tyrosine kinase]].<ref name="pmid27353087">{{cite journal |vauthors=Weiss A |title=Human LAT mutation results in immune deficiency and autoimmunity but also raises questions about signaling pathways |journal=J. Exp. Med. |volume=213 |issue=7 |pages=1114 |date=June 2016 |pmid=27353087 |pmc=4925028 |doi=10.1084/jem.2137insight1 |url=}}</ref>
* LAT is phosphorylated on multiple tyrosines and serve as docking sites for many effector molecules.
* Germ line LAT deficiency causes early [[thymocyte]] developmental arrest and complete absence of peripheral [[T cells]].
* LAT mutations results in premature LAT truncation, diminishing known tyrosine phosphorylation sites.
 
==DOCK2 Deficiency==
 
* Dedicator of cytokinesis 2 gene (DOCK2) deficiency is [[autosomal recessive]] disorder.<ref name="pmid26083206">{{cite journal |vauthors=Dobbs K, Domínguez Conde C, Zhang SY, Parolini S, Audry M, Chou J, Haapaniemi E, Keles S, Bilic I, Okada S, Massaad MJ, Rounioja S, Alwahadneh AM, Serwas NK, Capuder K, Çiftçi E, Felgentreff K, Ohsumi TK, Pedergnana V, Boisson B, Haskoloğlu Ş, Ensari A, Schuster M, Moretta A, Itan Y, Patrizi O, Rozenberg F, Lebon P, Saarela J, Knip M, Petrovski S, Goldstein DB, Parrott RE, Savas B, Schambach A, Tabellini G, Bock C, Chatila TA, Comeau AM, Geha RS, Abel L, Buckley RH, İkincioğulları A, Al-Herz W, Helminen M, Doğu F, Casanova JL, Boztuğ K, Notarangelo LD |title=Inherited DOCK2 Deficiency in Patients with Early-Onset Invasive Infections |journal=N. Engl. J. Med. |volume=372 |issue=25 |pages=2409–22 |date=June 2015 |pmid=26083206 |pmc=4480434 |doi=10.1056/NEJMoa1413462 |url=}}</ref>
* It causes defect in the chemokine-induced migration and actin polymerization.
* DOCK2 deficiency affects [[T cells]], [[B cells]] function and [[NK-cell]] degranulation.
 
==CARD11 Deficiency==
 
* It is [[autosomal recessive]] primary [[immunodeficiency]] with normal numbers of T and [[B lymphocytes]], but defective intracellular signaling.<ref name="pmid23374270">{{cite journal |vauthors=Stepensky P, Keller B, Buchta M, Kienzler AK, Elpeleg O, Somech R, Cohen S, Shachar I, Miosge LA, Schlesier M, Fuchs I, Enders A, Eibel H, Grimbacher B, Warnatz K |title=Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects |journal=J. Allergy Clin. Immunol. |volume=131 |issue=2 |pages=477–85.e1 |date=February 2013 |pmid=23374270 |doi=10.1016/j.jaci.2012.11.050 |url=}}</ref>
* Caspase recruitment domain 11 (CARD11) is fundamental signaling component that mediates TCR-induced NF-kappa B activation.<ref name="pmid12154356">{{cite journal |vauthors=Wang D, You Y, Case SM, McAllister-Lucas LM, Wang L, DiStefano PS, Nuñez G, Bertin J, Lin X |title=A requirement for CARMA1 in TCR-induced NF-kappa B activation |journal=Nat. Immunol. |volume=3 |issue=9 |pages=830–5 |date=September 2002 |pmid=12154356 |doi=10.1038/ni824 |url=}}</ref>
* Deficiency in CARD11 proceeds to impaired activation of NF-kappa B and also defect in interleukin-2 (IL-2) production.
 
==BCL10 Deficiency==
 
* BCL10 is an [[autosomal recessive]] disorder.<ref name="pmid25365219">{{cite journal |vauthors=Torres JM, Martinez-Barricarte R, García-Gómez S, Mazariegos MS, Itan Y, Boisson B, Rholvarez R, Jiménez-Reinoso A, del Pino L, Rodríguez-Pena R, Ferreira A, Hernández-Jiménez E, Toledano V, Cubillos-Zapata C, Díaz-Almirón M, López-Collazo E, Unzueta-Roch JL, Sánchez-Ramón S, Regueiro JR, López-Granados E, Casanova JL, Pérez de Diego R |title=Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity |journal=J. Clin. Invest. |volume=124 |issue=12 |pages=5239–48 |date=December 2014 |pmid=25365219 |pmc=4348943 |doi=10.1172/JCI77493 |url=}}</ref>
* Complete BCL10 deficiency affects both [[hematopoietic]] and nonhematopoietic immunity.
* It presents with Homozygous loss-of-expression and loss-of-function mutation of BCL10.
* NF-κB-mediated fibroblast functions were drastically affected.
 
==IKBKB Deficiency==
 
* IKBKB encodes IκB kinase 2 (IKK2, also known as IKKβ).<ref name="pmid24369075">{{cite journal |vauthors=Pannicke U, Baumann B, Fuchs S, Henneke P, Rensing-Ehl A, Rizzi M, Janda A, Hese K, Schlesier M, Holzmann K, Borte S, Laux C, Rump EM, Rosenberg A, Zelinski T, Schrezenmeier H, Wirth T, Ehl S, Schroeder ML, Schwarz K |title=Deficiency of innate and acquired immunity caused by an IKBKB mutation |journal=N. Engl. J. Med. |volume=369 |issue=26 |pages=2504–14 |date=December 2013 |pmid=24369075 |doi=10.1056/NEJMoa1309199 |url=}}</ref>
* Deficiency of IKBKB causes loss of expression of IKK2, also known as IKK-nuclear factor κB (NF-κB) pathway.
* IKBKB deficiency results in impairment of adaptive and innate [[immunity]].
 
==ICOS Deficiency==
 
* Inducible co-stimulator (ICOS) deficiency causes combined B- and T-cell [[immunodeficiency]].<ref name="pmid28861081">{{cite journal |vauthors=Schepp J, Chou J, Skrabl-Baumgartner A, Arkwright PD, Engelhardt KR, Hambleton S, Morio T, Röther E, Warnatz K, Geha R, Grimbacher B |title=14 Years after Discovery: Clinical Follow-up on 15 Patients with Inducible Co-Stimulator Deficiency |journal=Front Immunol |volume=8 |issue= |pages=964 |date=2017 |pmid=28861081 |pmc=5561331 |doi=10.3389/fimmu.2017.00964 |url=}}</ref>
* Genetic diagnosis is the only tool to differentiate ICOS deficiency from other immunological defects.
* Antibody deficiency, [[autoimmunity]], and combined [[immunodeficiency]] should be screened for ICOS mutations.
* ICOS deficiency was the first monogenic defect that cause common variable immunodeficiency (CVID)-like disease.
 
==TFRC Deficiency==
 
* TFRC deficiency is [[autosomal recessive]] disorder.<ref name="pmid26642240">{{cite journal |vauthors=Jabara HH, Boyden SE, Chou J, Ramesh N, Massaad MJ, Benson H, Bainter W, Fraulino D, Rahimov F, Sieff C, Liu ZJ, Alshemmari SH, Al-Ramadi BK, Al-Dhekri H, Arnaout R, Abu-Shukair M, Vatsayan A, Silver E, Ahuja S, Davies EG, Sola-Visner M, Ohsumi TK, Andrews NC, Notarangelo LD, Fleming MD, Al-Herz W, Kunkel LM, Geha RS |title=A missense mutation in TFRC, encoding transferrin receptor 1, causes combined immunodeficiency |journal=Nat. Genet. |volume=48 |issue=1 |pages=74–8 |date=January 2016 |pmid=26642240 |pmc=4696875 |doi=10.1038/ng.3465 |url=}}</ref>
* TFRC gene encodes the transferrin receptor, which is essential for cellular iron uptake.
* TFRC gene mutation causes defected TfR1 internalization motif and receptor [[endocytosis]].
 
==ReIB Deficiency==
 
* RelB is an NF-κB family [[transcription factor]].<ref name="urlRelB deficiency causes combined immunodeficiency - LymphoSign Journal">{{cite web |url=https://doi.org/10.14785/lpsn-2015-0005 |title=RelB deficiency causes combined immunodeficiency - LymphoSign Journal |format= |work= |accessdate=}}</ref>
* Homozygous mutation in the gene for the NFκB transcription factor RelB causes repeated infection.
* This mutation introduces a premature stop codon, which results in an ablation of RelB expression.
* There is diminished antibody response to [[immunizations]].
 
==CD40 ligand Deficiency==
 
* CD40 ligand (CD40L) deficiency leads to opportunistic infections.<ref name="pmid27554817">{{cite journal |vauthors=Cabral-Marques O, Ramos RN, Schimke LF, Khan TA, Amaral EP, Barbosa Bomfim CC, Junior OR, França TT, Arslanian C, Carola Correia Lima JD, Weber CW, Ferreira JF, Tavares FS, Sun J, D'Imperio Lima MR, Seelaender M, Garcia Calich VL, Marzagão Barbuto JA, Costa-Carvalho BT, Riemekasten G, Seminario G, Bezrodnik L, Notarangelo L, Torgerson TR, Ochs HD, Condino-Neto A |title=Human CD40 ligand deficiency dysregulates the macrophage transcriptome causing functional defects that are improved by exogenous IFN-γ |journal=J. Allergy Clin. Immunol. |volume=139 |issue=3 |pages=900–912.e7 |date=March 2017 |pmid=27554817 |doi=10.1016/j.jaci.2016.07.018 |url=}}</ref>
* CD40 ligand (CD154), present on activated CD4-positive [[T cells]].<ref name="pmid11687447">{{cite journal |vauthors=O'Gorman MR, DuChateau B, Paniagua M, Hunt J, Bensen N, Yogev R |title=Abnormal CD40 ligand (CD154) expression in human immunodeficiency virus-infected children |journal=Clin. Diagn. Lab. Immunol. |volume=8 |issue=6 |pages=1104–9 |date=November 2001 |pmid=11687447 |pmc=96233 |doi=10.1128/CDLI.8.6.1104-1109.2001 |url=}}</ref>
* Ligand for CD40 (CD40L) is a membrane glycoprotein on activated T cells that induces B cell proliferation and [[immunoglobulin]] secretion.<ref name="pmid7679801">{{cite journal |vauthors=Allen RC, Armitage RJ, Conley ME, Rosenblatt H, Jenkins NA, Copeland NG, Bedell MA, Edelhoff S, Disteche CM, Simoneaux DK |title=CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome |journal=Science |volume=259 |issue=5097 |pages=990–3 |date=February 1993 |pmid=7679801 |doi= |url=}}</ref>
* CD40L defects results in the failure of [[B cells]] to undergo immunoglobulin class switching.
 
==IL21R Deficiency==
 
* IL21R is type I cytokine receptors, which also include receptors for [[hematopoietic]] growth factors.<ref name="pmid11081504">{{cite journal |vauthors=Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA, Johnston J, Madden K, Xu W, West J, Schrader S, Burkhead S, Heipel M, Brandt C, Kuijper JL, Kramer J, Conklin D, Presnell SR, Berry J, Shiota F, Bort S, Hambly K, Mudri S, Clegg C, Moore M, Grant FJ, Lofton-Day C, Gilbert T, Rayond F, Ching A, Yao L, Smith D, Webster P, Whitmore T, Maurer M, Kaushansky K, Holly RD, Foster D |title=Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function |journal=Nature |volume=408 |issue=6808 |pages=57–63 |date=November 2000 |pmid=11081504 |doi=10.1038/35040504 |url=}}</ref>
* IL21R deficiency ceases proliferation and maturation of [[natural killer]] (NK) and [[B-cell]].
* IL21R deficiency also stop immunoglobulin class-switching in B cells, cytokine production in T cells, and NK cell cytotoxicity.<ref name="pmid23440042">{{cite journal |vauthors=Kotlarz D, Ziętara N, Uzel G, Weidemann T, Braun CJ, Diestelhorst J, Krawitz PM, Robinson PN, Hecht J, Puchałka J, Gertz EM, Schäffer AA, Lawrence MG, Kardava L, Pfeifer D, Baumann U, Pfister ED, Hanson EP, Schambach A, Jacobs R, Kreipe H, Moir S, Milner JD, Schwille P, Mundlos S, Klein C |title=Loss-of-function mutations in the IL-21 receptor gene cause a primary immunodeficiency syndrome |journal=J. Exp. Med. |volume=210 |issue=3 |pages=433–43 |date=March 2013 |pmid=23440042 |pmc=3600901 |doi=10.1084/jem.20111229 |url=}}</ref>
 
==MALT1 Deficiency==


==MAGT 1 Def:,LCK Def:, UNC119 Def:==
* [[MALT1]] vital for immune receptor-driven signaling pathways which leads to [[NF-κB]] activation.<ref name="pmid25762782">{{cite journal |vauthors=Bornancin F, Renner F, Touil R, Sic H, Kolb Y, Touil-Allaoui I, Rush JS, Smith PA, Bigaud M, Junker-Walker U, Burkhart C, Dawson J, Niwa S, Katopodis A, Nuesslein-Hildesheim B, Weckbecker G, Zenke G, Kinzel B, Traggiai E, Brenner D, Brüstle A, St Paul M, Zamurovic N, McCoy KD, Rolink A, Régnier CH, Mak TW, Ohashi PS, Patel DD, Calzascia T |title=Deficiency of MALT1 paracaspase activity results in unbalanced regulatory and effector T and B cell responses leading to multiorgan inflammation |journal=J. Immunol. |volume=194 |issue=8 |pages=3723–34 |date=April 2015 |pmid=25762782 |doi=10.4049/jimmunol.1402254 |url=}}</ref>
*Magnesium transporter gene (MAGT1) deficiency, T-cell tyrosine kinase Lck deficiency and Signaling adaptor protein Uncoordinated 119 (Unc119) deficiency related with a condition called Idiopathic CD4 lymphopenia. <ref name="pmid22184408">{{cite journal |vauthors=Gorska MM, Alam R |title=A mutation in the human Uncoordinated 119 gene impairs TCR signaling and is associated with CD4 lymphopenia |journal=Blood |volume=119 |issue=6 |pages=1399–406 |date=February 2012 |pmid=22184408 |pmc=3286207 |doi=10.1182/blood-2011-04-350686 |url=}}</ref>
* [[MALT1]] deficiency leads to reduced [[T cell]] proliferation, defective [[IL-2]] and [[TNF-α]] production, as well as impaired [[Th17 differentiation]].
*MAGT1 deficiency stops the Mg(2+) influx, which impairs responses to antigen receptor engagement and successive steps like activation of phospholipase Cγ1 and Ca(2+) influx in T cells but not B cells.<ref name="pmid21796205">{{cite journal |vauthors=Li FY, Chaigne-Delalande B, Kanellopoulou C, Davis JC, Matthews HF, Douek DC, Cohen JI, Uzel G, Su HC, Lenardo MJ |title=Second messenger role for Mg2+ revealed by human T-cell immunodeficiency |journal=Nature |volume=475 |issue=7357 |pages=471–6 |date=July 2011 |pmid=21796205 |pmc=3159560 |doi=10.1038/nature10246 |url=}}</ref>
* [[MALT1]] deficiency also impaired [[nuclear factor-κB]] activation and [[IL-2 production]].<ref name="pmid23727036">{{cite journal |vauthors=Jabara HH, Ohsumi T, Chou J, Massaad MJ, Benson H, Megarbane A, Chouery E, Mikhael R, Gorka O, Gewies A, Portales P, Nakayama T, Hosokawa H, Revy P, Herrod H, Le Deist F, Lefranc G, Ruland J, Geha RS |title=A homozygous mucosa-associated lymphoid tissue 1 (MALT1) mutation in a family with combined immunodeficiency |journal=J. Allergy Clin. Immunol. |volume=132 |issue=1 |pages=151–8 |date=July 2013 |pmid=23727036 |pmc=3700575 |doi=10.1016/j.jaci.2013.04.047 |url=}}</ref>
*Lck is vital for both CD4 and CD8 T-cell development and function. LCK deficiency decrease T cell proliferation.<ref name="pmid10744646">{{cite journal |vauthors=Hubert P, Bergeron F, Ferreira V, Seligmann M, Oksenhendler E, Debre P, Autran B |title=Defective p56Lck activity in T cells from an adult patient with idiopathic CD4+ lymphocytopenia |journal=Int. Immunol. |volume=12 |issue=4 |pages=449–57 |date=April 2000 |pmid=10744646 |doi= |url=}}</ref>
*Unc119 is necessary for activation of T-cell tyrosine kinase Lck. Unc119-deficiency reduce the activity of LCK and decrease interleukin 2 production and cellular proliferation.<ref name="pmid16966372">{{cite journal |vauthors=Lovatt M, Filby A, Parravicini V, Werlen G, Palmer E, Zamoyska R |title=Lck regulates the threshold of activation in primary T cells, while both Lck and Fyn contribute to the magnitude of the extracellular signal-related kinase response |journal=Mol. Cell. Biol. |volume=26 |issue=22 |pages=8655–65 |date=November 2006 |pmid=16966372 |pmc=1636771 |doi=10.1128/MCB.00168-06 |url=}}</ref>
==CD8 deficiency==
*CD8 glycoproteins play vital role in both the maturation and function of MHC class I-restricted T lymphocytes.
*CD8 deficiency is autosomal recessive familial condition.
*Single mutation in the CD8α gene that is due to missense mutation (gly90-->ser) in both alleles of the immunoglobulin domain of the CD8 alpha gene<ref name="pmid11435463">{{cite journal |vauthors=de la Calle-Martin O, Hernandez M, Ordi J, Casamitjana N, Arostegui JI, Caragol I, Ferrando M, Labrador M, Rodriguez-Sanchez JL, Espanol T |title=Familial CD8 deficiency due to a mutation in the CD8 alpha gene |journal=J. Clin. Invest. |volume=108 |issue=1 |pages=117–23 |date=July 2001 |pmid=11435463 |pmc=209336 |doi=10.1172/JCI10993 |url=}}</ref>
==ZETA-CHAIN-ASSOCIATED PROTEIN KINASE 70 (ZAP70) Deficiency==
*The ZAP70 gene encodes a tyrosine kinase that is a critical T-cell signaling.
*ZAP-70 deficiency, results in loss of the activity of this kinase<ref name="pmid8124727">{{cite journal |vauthors=Arpaia E, Shahar M, Dadi H, Cohen A, Roifman CM |title=Defective T cell receptor signaling and CD8+ thymic selection in humans lacking zap-70 kinase |journal=Cell |volume=76 |issue=5 |pages=947–58 |date=March 1994 |pmid=8124727 |doi= |url=}}</ref>
*ZAP70 is expressed mostly in T and NK cells, deficiency causes dysregulated T cells<ref name="pmid26783323">{{cite journal |vauthors=Chan AY, Punwani D, Kadlecek TA, Cowan MJ, Olson JL, Mathes EF, Sunderam U, Fu SM, Srinivasan R, Kuriyan J, Brenner SE, Weiss A, Puck JM |title=A novel human autoimmune syndrome caused by combined hypomorphic and activating mutations in ZAP-70 |journal=J. Exp. Med. |volume=213 |issue=2 |pages=155–65 |date=February 2016 |pmid=26783323 |pmc=4749924 |doi=10.1084/jem.20150888 |url=}}</ref>


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}

Latest revision as of 22:42, 28 January 2019


Immunodeficiency Main Page

Home

Overview

Classification

Immunodeficiency Affecting Cellular and Humoral Immunity

Combined Immunodeficiency

Predominantly Antibody Deficiency

Diseases of Immune Dysregulation

Congenital Defects of Phagocytes

Defects in Intrinsic and Innate Immunity

Auto-inflammatory Disorders

Complement Deficiencies

Phenocopies of Primary Immunodeficiency

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ali Akram, M.B.B.S.[2], Zahir Ali Shaikh, MD[3], Anmol Pitliya, M.B.B.S. M.D.[4], Syed Musadiq Ali M.B.B.S.[5]

Overview

Immunodeficiency disorders are associated with or predispose patients to various complications, including infections, autoimmune disorders, and lymphomas and other cancers. Primary immunodeficiencies are genetically determined and can be hereditary; secondary immunodeficiencies are acquired and much more common. combined immune defect affecting both types of acquired immunity, i.e. both cellular and humoral responses. Acquired immunity remembers when it encounters an invading foreign cell or molecule antigen and quickly mounts a specific response on subsequent encounters. Cellular acquired responses are mediated by T cells, also called T lymphocytes, which kill infected cells, help B cells, and control the immune response. Humoral immunity is mediated by B cells which produce antibodies immunoglobulins that help T cells and other immune cells to recognize and attack antigens.

Classification


 
 
Immunodeficiency affecting cellular and humoral immunity
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Severe combined immunodeficiencies SCID, defined
by CD3 T cell lymphopenia
 
Combined immunodeficiencies generally less pronounced
than severe combined immunodeficiency
 


Severe Combined Immunodeficiency (SCID)


 
 
 
 
 
 
 
 
 
Severe combined immunodeficiencies SCID, defined by CD3 T cell lymphopenia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CD19 NL: SCID T-ve B+ve
 
 
 
 
 
 
 
CD19 ↓: SCID T-ve B-ve
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SCID T-ve B+ve NK-ve
 
 
 
SCID T-ve B+ve NK+ve
 
SCID T-ve B-ve NK-ve
 
 
 
SCID T-ve B-ve NK+ve
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
yc deficiency
 
 
 
 
IL7Ra .
 
 
ADA def
 
Microcephaly present
 
 
Microcephaly absent
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
JAK-3 def
 
 
 
 
CD3D, CD3E, CD247
 
 
Reticular dysgenesis
 
 
 
DNA Ligase IV def
 
 
 
RAG1/2 def
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CD45 def
 
 
 
 
 
 
 
XLF def
 
 
 
DCLRE1C def
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coronin-1A def
 
 
 
 
 
 
 
DNA PKcs def
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Winged helix def
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Combined Immunodeficiencies Generally Less Pronounced than Severe Combined Immunodeficiency


 
 
 
 
 
 
 
 
 
 
 
 
 
Combined immunodeficiencies generally less pronounced than severe combined immunodeficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low CD4: MHC II Expression?
 
 
Low CD8
 
 
Low B Cells
 
 
 
Ig: Often Normal
 
 
Ig Low
 
 
Normal Ig but Low Specific Antibody Response
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Absent: MHCII deficiency
 
 
 
CD8 deficiency
 
 
 
DOCK8 deficiency
 
 
 
 
CD3Y deficiency
 
 
 
DOCK2 deficiency
 
 
 
IL2IR deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Present: MAGT 1 deficiency,LCK deficiency, UNC119 deficiency
 
 
 
ZAP70 deficiency
 
 
 
MST1 deficiency
 
 
 
 
RHOH deficiency
 
 
 
CARDII deficiency(LOF)
 
 
 
MALT1 deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MHC1 deficiency
 
 
 
IL21 deficiency
 
 
 
 
TCR alpha deficiency
 
 
 
BCL10 deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NIK deficiency
 
 
 
 
BCL11B deficiency
 
 
 
IKBKB deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Moesin deficiency
 
 
 
 
OX40 deficiency
 
 
 
ICOS deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
LAT deficiency
 
 
 
TFRC deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RelB deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CD40 ligand deficiency(CD154)
 
 
 
 
 
 
 


γc (IL-2Rγ) deficiency

JAK-3 deficiency

IL7a

CD3D

CD3E

CD247

CD45 deficiency

Coronin-1A deficiency

Winged helix deficiency/Nude SCID

ADA deficiency

Reticular dysgenesis

DNA Ligase IV deficiency

CERNUNNOS/XLF deficiency

DNA PKcs deficiency

RAG 1/2 deficiency

DCLRE1C deficiency

Combined Immunodeficiencies Generally Less Pronounced than Severe Combined Immunodeficiency

Major Histocompatibility Complex II Deficiency

Magnesium Transporter Gene (MAGT1) Deficiency, Lymphocyte-Specific Protein Tyrosine Kinase (LCK) Deficiency, UNC119 Deficiency

CD8 Deficiency

  • CD8 glycoproteins play vital role in both the maturation and function of MHC class I-restricted T lymphocytes.[36]
  • CD8 deficiency is autosomal recessive familial condition.
  • There is single mutation in the CD8α gene that is due to missense mutation (gly90-->ser) in both alleles of the immunoglobulin domain of the CD8 alpha gene.

Zeta-Chain-Associated Protein Kinase 70 (ZAP70) Deficiency

Major Histocompatibility Complex 1 Deficiency

Dedicator of Cytokinesis 8 (DOCK8) Deficiency

Macrophage Stimulating 1 Deficiency

Interleukin 21 Deficiency

NF-κB inducing kinase Deficiency

  • It is caused by mutation in MAP3K14.

Moesin Deficiency

CD3Y Deficiency

  • Deficiency of the CD3Y component of the TcR/CD3 complex is associated with a long-term severe defect of peripheral blood CD4+ CD45RA+ and CD8+ lymphocytes, whereas CD4+CD45RO+, B and natural killer lymphocytes are unaffected.[49]
  • These results suggest that the CD3Y site of the TcR/CD3 complex is required for the peripheral representation of certain T cell types.

RHOH Deficiency

  • Ras homolog gene family H (RhoH) is a membrane-bound adaptor protein that helps in proximal T-cell receptor signaling.[50]
  • Ras homolog gene family H (RHOH) deficiency leads to T cell defects and persistent HPV infections.[51]
  • RHOH encodes an atypical Rho GTPase expressed predominantly in hematopoietic cells.

T-cell Receptor Alpha Deficiency

  • The alpha chain is synthesized by recombination joining of single V segment with a J segment. Recombination of many different V segments with several J segments provides a wide range of antigen recognition.[52]
  • T-cell receptor-alpha deficiency is autosomal recessive disorder.[53]
  • It is caused by homozygous mutation in the TRAC gene on chromosome 14q11.

BCL11B Deficiency

  • BCL11B is required for T-cell differentiation and have vital role in the transcriptional regulation of these genes.[54]
  • BCL11B gene encodes a zinc-finger transcription factor involved in hematopoietic progenitor cell development.[55]
  • Bcl11b deficiency results in structural brain defects, reduced learning capacity, and impaired immune cell development.[56]

OX40 Deficiency

  • It is an autosomal recessive disorder. [57]
  • OX40 is a co-stimulatory receptor expressed on activated T cells.
  • Its ligand, OX40L, is expressed on various cell types, including endothelial cells.
  • OX40L was abundantly expressed in Kaposi Sarcoma lesions.
  • OX40 deficiency causes low proportion of effector memory CD4(+) T cells in the peripheral blood.

LAT Deficiency

  • Linker for Activation of T cell (LAT) is substrate of the ZAP70 tyrosine kinase.[58]
  • LAT is phosphorylated on multiple tyrosines and serve as docking sites for many effector molecules.
  • Germ line LAT deficiency causes early thymocyte developmental arrest and complete absence of peripheral T cells.
  • LAT mutations results in premature LAT truncation, diminishing known tyrosine phosphorylation sites.

DOCK2 Deficiency

  • Dedicator of cytokinesis 2 gene (DOCK2) deficiency is autosomal recessive disorder.[59]
  • It causes defect in the chemokine-induced migration and actin polymerization.
  • DOCK2 deficiency affects T cells, B cells function and NK-cell degranulation.

CARD11 Deficiency

  • It is autosomal recessive primary immunodeficiency with normal numbers of T and B lymphocytes, but defective intracellular signaling.[60]
  • Caspase recruitment domain 11 (CARD11) is fundamental signaling component that mediates TCR-induced NF-kappa B activation.[61]
  • Deficiency in CARD11 proceeds to impaired activation of NF-kappa B and also defect in interleukin-2 (IL-2) production.

BCL10 Deficiency

  • BCL10 is an autosomal recessive disorder.[62]
  • Complete BCL10 deficiency affects both hematopoietic and nonhematopoietic immunity.
  • It presents with Homozygous loss-of-expression and loss-of-function mutation of BCL10.
  • NF-κB-mediated fibroblast functions were drastically affected.

IKBKB Deficiency

  • IKBKB encodes IκB kinase 2 (IKK2, also known as IKKβ).[63]
  • Deficiency of IKBKB causes loss of expression of IKK2, also known as IKK-nuclear factor κB (NF-κB) pathway.
  • IKBKB deficiency results in impairment of adaptive and innate immunity.

ICOS Deficiency

  • Inducible co-stimulator (ICOS) deficiency causes combined B- and T-cell immunodeficiency.[64]
  • Genetic diagnosis is the only tool to differentiate ICOS deficiency from other immunological defects.
  • Antibody deficiency, autoimmunity, and combined immunodeficiency should be screened for ICOS mutations.
  • ICOS deficiency was the first monogenic defect that cause common variable immunodeficiency (CVID)-like disease.

TFRC Deficiency

  • TFRC deficiency is autosomal recessive disorder.[65]
  • TFRC gene encodes the transferrin receptor, which is essential for cellular iron uptake.
  • TFRC gene mutation causes defected TfR1 internalization motif and receptor endocytosis.

ReIB Deficiency

  • RelB is an NF-κB family transcription factor.[66]
  • Homozygous mutation in the gene for the NFκB transcription factor RelB causes repeated infection.
  • This mutation introduces a premature stop codon, which results in an ablation of RelB expression.
  • There is diminished antibody response to immunizations.

CD40 ligand Deficiency

  • CD40 ligand (CD40L) deficiency leads to opportunistic infections.[67]
  • CD40 ligand (CD154), present on activated CD4-positive T cells.[68]
  • Ligand for CD40 (CD40L) is a membrane glycoprotein on activated T cells that induces B cell proliferation and immunoglobulin secretion.[69]
  • CD40L defects results in the failure of B cells to undergo immunoglobulin class switching.

IL21R Deficiency

  • IL21R is type I cytokine receptors, which also include receptors for hematopoietic growth factors.[70]
  • IL21R deficiency ceases proliferation and maturation of natural killer (NK) and B-cell.
  • IL21R deficiency also stop immunoglobulin class-switching in B cells, cytokine production in T cells, and NK cell cytotoxicity.[45]

MALT1 Deficiency

References

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  2. Fred S. Rosen (2002). "Successful gene therapy for severe combined immunodeficiency". The New England journal of medicine. 346 (16): 1241–1243. doi:10.1056/NEJM200204183461612. PMID 11961154. Unknown parameter |month= ignored (help)
  3. F. Candotti, S. A. Oakes, J. A. Johnston, S. Giliani, R. F. Schumacher, P. Mella, M. Fiorini, A. G. Ugazio, R. Badolato, L. D. Notarangelo, F. Bozzi, P. Macchi, D. Strina, P. Vezzoni, R. M. Blaese, J. J. O'Shea & A. Villa (1997). "Structural and functional basis for JAK3-deficient severe combined immunodeficiency". Blood. 90 (10): 3996–4003. PMID 9354668. Unknown parameter |month= ignored (help)
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