Predominantly antibody deficiency
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Immunodeficiency Main Page |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ali Akram, M.B.B.S.[2], Anmol Pitliya, M.B.B.S. M.D.[3]
Overview
Classification
| Predominantly antibody deficiencies | |||||||||||||||
| Hypogammaglobulinemia | Other antibody deficiencies | ||||||||||||||
Hypogammaglobulinemia
| Predominantly antibody deficiencies (A): Hypogammaglobulinemia | |||||||||||||||||||||||||||||||
| Serum immunoglobulin assays : IgG, IgA, IgM, IgE | |||||||||||||||||||||||||||||||
| IgG, IgA, and/or IgM ↓↓ → B Lymphocyte (CD19+) enumeration (CMF) | |||||||||||||||||||||||||||||||
| B absent | B >1% | ||||||||||||||||||||||||||||||
| X-Linked Agammaglobulinemia | Common Variable Immunodeficiency Phenotype | CD19 deficiency | |||||||||||||||||||||||||||||
| µ heavy chain Def | CVID with no gene defect specified | CD20 deficiency | |||||||||||||||||||||||||||||
| Igα def | PIK3CD mutation(GOF),PIK3R1 deficiency(LOF) | CD21 deficiency | |||||||||||||||||||||||||||||
| Igβ def | PTEN deficiency(LOF) | TRNT1 deficiency | |||||||||||||||||||||||||||||
| BLNK def | CD81 deficiency | NFKB1 deficiency | |||||||||||||||||||||||||||||
| λ5 def | TACI deficiency | NFKB2 deficiency | |||||||||||||||||||||||||||||
| PI3KR1 def | BAFF receptor deficiency | IKAROS deficiency | |||||||||||||||||||||||||||||
| E47 transcription factor def | TWEAK deficiency | ATP6AP1 deficiency | |||||||||||||||||||||||||||||
| Mannosyl-oligosaccharide glucosidase deficiency (MOGS) | |||||||||||||||||||||||||||||||
| TTC37 deficiency | |||||||||||||||||||||||||||||||
| IRF2BP2 deficiency | |||||||||||||||||||||||||||||||
Other Antibody deficiencies
| Predominantly antibody deficiencies (B): Other antibody deficiencies | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Serum Immunolobulin Assays: IgG, IgA, IgM, IgE | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe Reduction in Serum IgG and IgA with NI/elevated IgM and Normal Numbers of B cells: Hyper IgM Syndromes | Isotype, Light Chain, or Functional Deficiencies with Generally NI Numbers of B cells | High B cell numbers due to constitutive NF-kB activation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| AID deficiency | Selective IgA deficiency | CARD11 Gain of Function | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| UNG deficiency | Transient hypogammaglobuliemia of infancy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| INO80 | IgG subclass deficiency with IgA deficiency | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| MSH6 | Isolated IgG subclass deficiency | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Specific antibody deficiency with normal Ig levels and normal B cells | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ig heavy chain muations and deletions | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Kappa chain deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Selective IgM deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
X-linked Agammaglobulinemia
- It is an X linked disease, first described by Bruton in 1952.
- It is caused by the mutation of BTK gene (present on the long arm of X chromosome) which encodes for the protein Bruton tyrosine kinase,which is associated with the maturation and differentiation of the pre B cell.[1]
- The disruption of this protein can lead to significant decrease in all antibody isotypes, due to failure of Ig heavy chain rearrangement.[2]
- Affected individuals generally present between 3 months to 3 years of age, with almost 90% becoming symptomatic by 5 years of age.[3]
- Presence of maternal immunoglobulins provide transient protection, concealing symptoms of the disease and preventing early detection.
- Physical examination typically shows absence of lymph nodes.
- Patients are susceptible to recurrent infections with encapsulated organisms and enteroviruses, primarily effecting respiratory and gastrointestinal tracts.
- Laboratory findings show defect in humoral immunity with absence or negligible amount of IgM, IgG, and IgA, as well as <2% of B cells lymphocytes. Neutropenia can also be seen.[4][1][5]
- Treatment is mainly via hematopoietic stem cell therapy and through replacement of immunoglobulins either by intravenous or subcutaneous routes. Recurrent infections are prevented and treated by antibiotics.[6]
For more information on X-linked agammaglobulinemia, click here.
µ Heavy Chain Deficiency
- Autosomal recessive (AR) transmission.
- It is caused by mutation of µ heavy chain (IGHM) on chromosome 14.[7]
- This mutation is phenotypically similar to X-linked agammaglobulinemia, but unlike X-linked agammaglobulinemia can also be seen in females, yet there has been a study that provides data showing clinically significant difference between the two.[8]
- Treatment is mainly via replacement of immunoglobulins by intravenous or subcutaneous routes, hematopoietic stem cell therapy and use of prophylactic and curative antibiotics.[6]
Igα Deficiency
- Autosomal recessive (AR) transmission.
- Mutation of Igα(CD79α) a component of B cell receptor (BCR). Mutations in Pre-BCR complex many times lead to truncation of B cell development.
- It causes a B cell defect which leads to a clinical picture similar to X-linked agammaglobulinemia.
- Patients have increased susceptibility to bacterial infections and otitis media.
- Diagnosis is mainly by polymerase chain reaction (PCR) or single starnd conformational polymosrphism analysis(SSCA).[9]
- Treatment is mainly through replacement of immunoglobulins by intravenous or subcutaneous routes, hematopoietic stem cell therapy and use of prophylactic and curative antibiotics.[10].
Igβ Deficiency
- Igβ deficiency has autosomal recessive (AR) transmission.
- Caused by mutation in the CD79B gene on chromosome 17.
- Igβ is a signal transduction molecule similar to Igα and is essential for B cell receptor(BCR) expression.
- Patients generally present with reduced immunoglobulins which leads to frequent bacterial infections of upper and lower respiratory tract similar to other agammaglobulinemia like X-linked agammaglobulinemia.[11][12]
- Treatment is mainly via replacement of immunoglobulins by intravenous or subcutaneous routes, hematopoietic stem cell therapy and use of prophylactic and curative antibiotics.[12]
BLNK Deficiency
- BLNK deficiency has autosomal recessive (AR) transmission.
- BLNK gene on chromosome 10 encodes for a scaffold molecule B cell linker protein (BLNK, SLC-65) and is crucial for the development of pre B cell.
- Patients generally present with recurrent bacterial infections, otitis media and upper and lower respiratory tract infections similar to X-linked agammaglobulinemia.[13]
- Treatment is mainly via replacement of immunoglobulins by intravenous or subcutaneous routes, hematopoietic stem cell therapy and use of prophylactic and curative antibiotics.[10]
λ5 Deficiency
- λ5 deficiency has autosomal recessive (AR) transmission..
- It is caused by mutation of λ5 (IGLL1), component of B cell receptor, on chromosome 22.
- Leads to clinical features similar to X-linked agammaglobulinemia.[14]
- Treatment is mainly through replacement of immunoglobulins by intravenous or subcutaneous routes, hematopoietic stem cell therapy and use of prophylactic and curative antibiotics.[10]
PI3KR1 Deficiency
- PIK3R1 gene encodes for the p85α subunit of class IA phosphoinositide 3-kinases (PI3Ks).[15]
- Patients present with history of recurrent bacterial infections and positive family history, similar to clinical features seen in X-linked agammaglobulinemia.[16]
- Treatment is mainly through replacement of immunoglobulins by intravenous or subcutaneous routes, hematopoietic stem cell therapy and use of prophylactic and curative antibiotics.[10]
E47 transcription factor Deficiency
- Mutation of E47 transcription factor.
- This mutation leads to improper differentiation of B cell from lymphoid precursors.[17]
- Patients present with few B cells characterized increased expression of CD19, but without B cell receptor (BCR).[18]
- Treatment is mainly through replacement of immunoglobulins by intravenous or subcutaneous routes, hematopoietic stem cell therapy and use of prophylactic and curative antibiotics.[10]
CVID With No Gene Specified
- Common variable immune deficiency (CVID) is the most common primary immune deficiency presenting in adult patients.
- Patients show symptoms of disease later in life and the cause is mainly polygenic.[19]
- CVID is a diagnosis of exclusion due to its varied etiology.
- The ESID/PAGID criteria is for diagnosis is:
- Hypogammaglobulinaemia with IgG levels two standard deviations below the mean.
- Impaired vaccine responses or absent isohemagglutinins.
- Exclusion of other causes of hypogammaglobulinaemia.
- Patients are susceptible to recurrent infections, autoimmunity and malignancy.
- Treatment is by intravenous or subcutaneous replacement of immunoglobulins.[20]
PIK3CD mutation,PIK3R1 deficiency
- Also known as Activated phosphoinositide 3-kinase δ syndrome (APDS).
- Autosomal dominant gain of function (GOF) mutation of PIK3CD gene, which encodes for P110δ subunit of phosphoinositide 3-kinase (PI3K) and loss of function (LOF) mutation of PIK3R1 gene, which encodes the p85α subunit of PI3K.
- Mutations in PIK3CD gene leads to clinical features similar to mutation in PIK3R1 gene.[21]
- Patients with mutations of gene for PIK3R1 show characteristics similar to that of patients carrying gain-of-function mutations of PIK3CD gene.
- Mutations lead to hyperactive PI3K/AKT/mTOR signaling.[15][22]
- Disease is characterized by low numbers of naive T cells, but a larger number of senescent effector T cells.
- Patients present with upper and lower respiratory tract infections, lymphadenopathy, nodular lymphoid hyperplasia, early-onset autoimmunity, malignancies and recurrent viral infections with cytomegalovirus (CMV) and Epstein Barr virus (EBV).[23]
- Treatment is via sirolimus and selective PI3Kδ inhibitors, intavenous and subcutaneous immunoglobulin replacement, prophylactic antibiotic, and hematopoietic stem cell transplant.[24]
PTEN deficiency
- Phosphatase and tensin homolog (PTEN) is an inhibitory component of phosphoinositide 3-kinase (PI3K) signalling network.[25]
- Loss of function mutation of this gene leads to up regulation of PI3K/AKT/mTOR pathway leading to APDS like immunodeficiency.
- Immunodeficiency leads to recurrent infections, Cowden disease and malignancies.
- Treatment is by intravenous and subcutaneous immunoglobulin and antibiotics.[26]
CD 81 Deficiency
- CD81 is a B cell surface protein (part of CD19 complex) which helps in antigen recognition.
- Deficiency is characterized by decreased in number of B cell, hypogammaglobulinemia , impaired antibody responses, and absence of CD19 expression on B cells.
- Patients present with recurrent infections of upper and lower respiratory tract.
- Treatment is mainly through replacement of immunoglobulins by intravenous or subcutaneous routes, hematopoietic stem cell therapy and use of prophylactic and curative antibiotics.[27]
TACI Deficiency
- Transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) is a part of tumor necrosis factor family and involved in B cell class switching.
- Missense mutation of one allele of TNFRSF13B gene encoding for TACI leads to CVID like immunodeficiency.[28]
- Patients present with increased suseptability to encapsulated organisms, autoimmunity, and hypogammaglobulinemia.[29][30]
- Treatment is by intravenous or subcutaneous replacement of immunoglobulins.[20]
BAFF Receptor Deficiency
- Mutation of B-cell activating factor receptor (BAFF-R) prevents maturation of transitional B cell, leading to a CVID type adult onset immunodeficiency.
- Incomplete maturation leads to hypogammaglobulinemia, but can in a few cases not manifest to clinical disease, with recurrent infections.
- Patients show symptoms varying from severe immunodeficiency to a mild form of hypogammaglobulinemia.[31]
- Treatment is by intravenous or subcutaneous replacement of immunoglobulins and by curative antibiotics.[20]
References
- ↑ 1.0 1.1 Hernandez-Trujillo VP, Scalchunes C, Cunningham-Rundles C, Ochs HD, Bonilla FA, Paris K, Yel L, Sullivan KE (August 2014). "Autoimmunity and inflammation in X-linked agammaglobulinemia". J. Clin. Immunol. 34 (6): 627–32. doi:10.1007/s10875-014-0056-x. PMC 4157090. PMID 24909997.
- ↑ Rawlings DJ, Witte ON (April 1994). "Bruton's tyrosine kinase is a key regulator in B-cell development". Immunol. Rev. 138: 105–19. PMID 8070812.
- ↑ Winkelstein JA, Marino MC, Lederman HM, Jones SM, Sullivan K, Burks AW, Conley ME, Cunningham-Rundles C, Ochs HD (July 2006). "X-linked agammaglobulinemia: report on a United States registry of 201 patients". Medicine (Baltimore). 85 (4): 193–202. doi:10.1097/01.md.0000229482.27398.ad. PMID 16862044.
- ↑ Fried AJ, Bonilla FA (July 2009). "Pathogenesis, diagnosis, and management of primary antibody deficiencies and infections". Clin. Microbiol. Rev. 22 (3): 396–414. doi:10.1128/CMR.00001-09. PMC 2708392. PMID 19597006.
- ↑ Berglöf A, Turunen JJ, Gissberg O, Bestas B, Blomberg KE, Smith CI (December 2013). "Agammaglobulinemia: causative mutations and their implications for novel therapies". Expert Rev Clin Immunol. 9 (12): 1205–21. doi:10.1586/1744666X.2013.850030. PMID 24215410.
- ↑ 6.0 6.1 Cunningham-Rundles C (June 2011). "Key aspects for successful immunoglobulin therapy of primary immunodeficiencies". Clin. Exp. Immunol. 164 Suppl 2: 16–9. doi:10.1111/j.1365-2249.2011.04390.x. PMC 3087906. PMID 21466548.
- ↑ Yel L, Minegishi Y, Coustan-Smith E, Buckley RH, Trübel H, Pachman LM, Kitchingman GR, Campana D, Rohrer J, Conley ME (November 1996). "Mutations in the mu heavy-chain gene in patients with agammaglobulinemia". N. Engl. J. Med. 335 (20): 1486–93. doi:10.1056/NEJM199611143352003. PMID 8890099.
- ↑ Abolhassani H, Vitali M, Lougaris V, Giliani S, Parvaneh N, Parvaneh L, Mirminachi B, Cheraghi T, Khazaei H, Mahdaviani SA, Kiaei F, Tavakolinia N, Mohammadi J, Negahdari B, Rezaei N, Hammarstrom L, Plebani A, Aghamohammadi A (2016). "Cohort of Iranian Patients with Congenital Agammaglobulinemia: Mutation Analysis and Novel Gene Defects". Expert Rev Clin Immunol. 12 (4): 479–86. doi:10.1586/1744666X.2016.1139451. PMID 26910880.
- ↑ Wang Y, Kanegane H, Sanal O, Tezcan I, Ersoy F, Futatani T, Miyawaki T (April 2002). "Novel Igalpha (CD79a) gene mutation in a Turkish patient with B cell-deficient agammaglobulinemia". Am. J. Med. Genet. 108 (4): 333–6. PMID 11920841.
- ↑ 10.0 10.1 10.2 10.3 10.4 Maarschalk-Ellerbroek LJ, Hoepelman IM, Ellerbroek PM (May 2011). "Immunoglobulin treatment in primary antibody deficiency". Int. J. Antimicrob. Agents. 37 (5): 396–404. doi:10.1016/j.ijantimicag.2010.11.027. PMID 21276714.
- ↑ Ferrari S, Lougaris V, Caraffi S, Zuntini R, Yang J, Soresina A, Meini A, Cazzola G, Rossi C, Reth M, Plebani A (September 2007). "Mutations of the Igbeta gene cause agammaglobulinemia in man". J. Exp. Med. 204 (9): 2047–51. doi:10.1084/jem.20070264. PMC 2118692. PMID 17709424.
- ↑ 12.0 12.1 Dobbs AK, Yang T, Farmer D, Kager L, Parolini O, Conley ME (August 2007). "Cutting edge: a hypomorphic mutation in Igbeta (CD79b) in a patient with immunodeficiency and a leaky defect in B cell development". J. Immunol. 179 (4): 2055–9. PMID 17675462.
- ↑ Minegishi Y, Rohrer J, Coustan-Smith E, Lederman HM, Pappu R, Campana D, Chan AC, Conley ME (December 1999). "An essential role for BLNK in human B cell development". Science. 286 (5446): 1954–7. PMID 10583958.
- ↑ Minegishi Y, Coustan-Smith E, Wang YH, Cooper MD, Campana D, Conley ME (January 1998). "Mutations in the human lambda5/14.1 gene result in B cell deficiency and agammaglobulinemia". J. Exp. Med. 187 (1): 71–7. PMC 2199185. PMID 9419212.
- ↑ 15.0 15.1 Deau MC, Heurtier L, Frange P, Suarez F, Bole-Feysot C, Nitschke P, Cavazzana M, Picard C, Durandy A, Fischer A, Kracker S (September 2014). "A human immunodeficiency caused by mutations in the PIK3R1 gene". J. Clin. Invest. 124 (9): 3923–8. doi:10.1172/JCI75746. PMC 4153704. PMID 25133428.
- ↑ de la Morena M, Haire RN, Ohta Y, Nelson RP, Litman RT, Day NK, Good RA, Litman GW (March 1995). "Predominance of sterile immunoglobulin transcripts in a female phenotypically resembling Bruton's agammaglobulinemia". Eur. J. Immunol. 25 (3): 809–15. doi:10.1002/eji.1830250327. PMID 7705412.
- ↑ Boisson B, Wang YD, Bosompem A, Ma CS, Lim A, Kochetkov T, Tangye SG, Casanova JL, Conley ME (November 2013). "A recurrent dominant negative E47 mutation causes agammaglobulinemia and BCR(-) B cells". J. Clin. Invest. 123 (11): 4781–5. doi:10.1172/JCI71927. PMC 3809807. PMID 24216514.
- ↑ Dobbs AK, Bosompem A, Coustan-Smith E, Tyerman G, Saulsbury FT, Conley ME (August 2011). "Agammaglobulinemia associated with BCR⁻ B cells and enhanced expression of CD19". Blood. 118 (7): 1828–37. doi:10.1182/blood-2011-01-330472. PMC 3158715. PMID 21693761.
- ↑ Park JH, Resnick ES, Cunningham-Rundles C (December 2011). "Perspectives on common variable immune deficiency". Ann. N. Y. Acad. Sci. 1246: 41–9. doi:10.1111/j.1749-6632.2011.06338.x. PMC 3428018. PMID 22236429.
- ↑ 20.0 20.1 20.2 Ameratunga R, Woon ST, Gillis D, Koopmans W, Steele R (November 2013). "New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin". Clin. Exp. Immunol. 174 (2): 203–11. doi:10.1111/cei.12178. PMC 3828823. PMID 23859429.
- ↑ Ochs HD (December 2014). "Common variable immunodeficiency (CVID): new genetic insight and unanswered questions". Clin. Exp. Immunol. 178 Suppl 1: 5–6. doi:10.1111/cei.12491. PMC 4285471. PMID 25546742.
- ↑ Coulter TI, Chandra A, Bacon CM, Babar J, Curtis J, Screaton N, Goodlad JR, Farmer G, Steele CL, Leahy TR, Doffinger R, Baxendale H, Bernatoniene J, Edgar JD, Longhurst HJ, Ehl S, Speckmann C, Grimbacher B, Sediva A, Milota T, Faust SN, Williams AP, Hayman G, Kucuk ZY, Hague R, French P, Brooker R, Forsyth P, Herriot R, Cancrini C, Palma P, Ariganello P, Conlon N, Feighery C, Gavin PJ, Jones A, Imai K, Ibrahim MA, Markelj G, Abinun M, Rieux-Laucat F, Latour S, Pellier I, Fischer A, Touzot F, Casanova JL, Durandy A, Burns SO, Savic S, Kumararatne DS, Moshous D, Kracker S, Vanhaesebroeck B, Okkenhaug K, Picard C, Nejentsev S, Condliffe AM, Cant AJ (February 2017). "Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study". J. Allergy Clin. Immunol. 139 (2): 597–606.e4. doi:10.1016/j.jaci.2016.06.021. PMC 5292996. PMID 27555459.
- ↑ Lucas CL, Kuehn HS, Zhao F, Niemela JE, Deenick EK, Palendira U, Avery DT, Moens L, Cannons JL, Biancalana M, Stoddard J, Ouyang W, Frucht DM, Rao VK, Atkinson TP, Agharahimi A, Hussey AA, Folio LR, Olivier KN, Fleisher TA, Pittaluga S, Holland SM, Cohen JI, Oliveira JB, Tangye SG, Schwartzberg PL, Lenardo MJ, Uzel G (January 2014). "Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110δ result in T cell senescence and human immunodeficiency". Nat. Immunol. 15 (1): 88–97. doi:10.1038/ni.2771. PMC 4209962. PMID 24165795.
- ↑ Maccari ME, Abolhassani H, Aghamohammadi A, Aiuti A, Aleinikova O, Bangs C, Baris S, Barzaghi F, Baxendale H, Buckland M, Burns SO, Cancrini C, Cant A, Cathébras P, Cavazzana M, Chandra A, Conti F, Coulter T, Devlin LA, Edgar J, Faust S, Fischer A, Garcia-Prat M, Hammarström L, Heeg M, Jolles S, Karakoc-Aydiner E, Kindle G, Kiykim A, Kumararatne D, Grimbacher B, Longhurst H, Mahlaoui N, Milota T, Moreira F, Moshous D, Mukhina A, Neth O, Neven B, Nieters A, Olbrich P, Ozen A, Pachlopnik Schmid J, Picard C, Prader S, Rae W, Reichenbach J, Rusch S, Savic S, Scarselli A, Scheible R, Sediva A, Sharapova SO, Shcherbina A, Slatter M, Soler-Palacin P, Stanislas A, Suarez F, Tucci F, Uhlmann A, van Montfrans J, Warnatz K, Williams AP, Wood P, Kracker S, Condliffe AM, Ehl S (2018). "Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3-Kinase δ Syndrome: The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry". Front Immunol. 9: 543. doi:10.3389/fimmu.2018.00543. PMC 5863269. PMID 29599784. Vancouver style error: initials (help)
- ↑ Leslie NR, Longy M (April 2016). "Inherited PTEN mutations and the prediction of phenotype". Semin. Cell Dev. Biol. 52: 30–8. doi:10.1016/j.semcdb.2016.01.030. PMID 26827793.
- ↑ Tsujita Y, Mitsui-Sekinaka K, Imai K, Yeh TW, Mitsuiki N, Asano T, Ohnishi H, Kato Z, Sekinaka Y, Zaha K, Kato T, Okano T, Takashima T, Kobayashi K, Kimura M, Kunitsu T, Maruo Y, Kanegane H, Takagi M, Yoshida K, Okuno Y, Muramatsu H, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Kojima S, Ogawa S, Ohara O, Okada S, Kobayashi M, Morio T, Nonoyama S (December 2016). "Phosphatase and tensin homolog (PTEN) mutation can cause activated phosphatidylinositol 3-kinase δ syndrome-like immunodeficiency". J. Allergy Clin. Immunol. 138 (6): 1672–1680.e10. doi:10.1016/j.jaci.2016.03.055. PMID 27426521.
- ↑ van Zelm MC, Smet J, Adams B, Mascart F, Schandené L, Janssen F, Ferster A, Kuo CC, Levy S, van Dongen JJ, van der Burg M (April 2010). "CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency". J. Clin. Invest. 120 (4): 1265–74. doi:10.1172/JCI39748. PMC 2846042. PMID 20237408.
- ↑ Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, Geha RS (August 2005). "TACI is mutant in common variable immunodeficiency and IgA deficiency". Nat. Genet. 37 (8): 829–34. doi:10.1038/ng1601. PMID 16007086.
- ↑ Tsuji S, Cortesão C, Bram RJ, Platt JL, Cascalho M (November 2011). "TACI deficiency impairs sustained Blimp-1 expression in B cells decreasing long-lived plasma cells in the bone marrow". Blood. 118 (22): 5832–9. doi:10.1182/blood-2011-05-353961. PMC 3228499. PMID 21984806.
- ↑ Martinez-Gallo M, Radigan L, Almejún MB, Martínez-Pomar N, Matamoros N, Cunningham-Rundles C (February 2013). "TACI mutations and impaired B-cell function in subjects with CVID and healthy heterozygotes". J. Allergy Clin. Immunol. 131 (2): 468–76. doi:10.1016/j.jaci.2012.10.029. PMC 3646641. PMID 23237420.
- ↑ Warnatz K, Salzer U, Rizzi M, Fischer B, Gutenberger S, Böhm J, Kienzler AK, Pan-Hammarström Q, Hammarström L, Rakhmanov M, Schlesier M, Grimbacher B, Peter HH, Eibel H (August 2009). "B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans". Proc. Natl. Acad. Sci. U.S.A. 106 (33): 13945–50. doi:10.1073/pnas.0903543106. PMC 2722504. PMID 19666484.