Lymphoproliferative disorders

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Lymphoproliferative disorders
ICD-9 238.79
eMedicine ped/1345 
MeSH D008232

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1],

Synonyms and keywords: B cell proliferation, T cell proliferation, LPD, lymphoproliferation, lymphoproliferative neoplasm

Overview

Lymphoproliferative disorders refer to several conditions of lymphatic diseases in which lymphocytes are produced in excessive quantities[1]. They typically occur in patients who have compromised immune systems. They are sometimes equated with "immunoproliferative disorders", but technically lymphoproliferative disorders are a subset of immunoproliferative disorders, along with hypergammaglobulinemia and paraproteinemias.

Examples of LPDs

Types

Lymphoproliferative disorders are a set of disorders characterized by the abnormal proliferation of lymphocytes into a monoclonal lymphocytosis. The two major types of lymphocytes are B cells and T cells, which are derived from pleuripotent hematopoetic stem cells in the bone marrow. Individuals who have some sort of immunodysfuction are susceptible to developing a lymphoproliferative disorder because when any of the numerous control points of the immune system become dysfunctional, immunodeficiency or deregulation of lymphocytes is more likely to occur. There are several inherited gene mutations that have been identified to cause lymphoproliferative disorders, however there are also acquired and iatrogenic causes.[2]

X-linked Lymphoproliferative disorder

There is a mutation on the X chromosome that has been found to be associated with a T and NK cell lymphoproliferative disorder.

Autosomal lymphoproliferative disorder

Some children with autoimmune lymphoproliferative disorders are heterozygous for a mutation in the gene that codes for the Fas receptor, which is located on the long arm of chromosome 10 at position 24.1, denoted 10q24.1.[3] This gene is member 6 of the TNF-receptor superfamily (TNFSF6). The Fas receptor contains a death domain and has been shown to play a central role in the physiological regulation of programmed cell death. Normally, stimulation of recently activated T cells by antigen leads to coexpression of Fas and Fas receptor on the T cell surface. The engagement of Fas by Fas receptor results in apoptosis of the cell and is important for eliminating T cells that are repeatedly stimulated by antigens.[4] As a result of the mutation in the Fas receptor gene, there is no recognition of Fas by Fas receptor, leading to a primitive population of T cells that proliferates in an uncontrolled manner.[2]

Other inherited causes

Boys with X-linked immunodeficiency syndrome are at a higher risk of mortality associated with EBV infections, and are predisposed to develop a lymphoproliferative disorder or lymphoma.

Children with common variable immune deficiency (CVID) are also at a higher risk of developing a lymphoproliferative disorder.

Some disorders that predispose a person to lymphoproliferative disorders are severe combined immuno deficiency (SCID), Chédiak-Higashi syndrome, Wiskott-Aldrich syndrome (an X-linked recessive disorder) and Ataxia telangiectasia.

Interestingly, even though Ataxia telangiectasia is an autosomal recessive disorder, people who are heterozygotes for this still have an increased risk of developing a lymphoproliferative disorder.[2]

Acquired causes

Viral infection is a very common cause of lymphoproliferative disorders. The most common is congenital HIV infection because it is highly associated with acquired immunodeficiency, which often leads to lymphoproliferative disorders.[2]

Iatrogenic causes

There are many lymphoproliferative disorders that are associated with organ transplantation and immunosuppressant therapies. In most reported cases, these cause B cell lymphoproliferative disorders, however some T cell variations have been described.[2] The T cell variations are usually caused by the prolonged use of T cell suppressant drugs, such as sirolimus, tacrolimus belatacept or cyclosporine A.[2]

See also

References

  1. Anonymous (2024), Lymphoproliferative disorders (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 Winter, S.S. Lymphoproliferative disorders. Emedicine. December 20, 2006. http://www.emedicine.com/ped/topic1345.htm. Accessed March 2007.
  3. Entrez Gene. FAS Fas (TNF receptor superfamily, member 6). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=gene&dopt=full_report&list_uids=355. Accessed March 2007.
  4. Abbas, A.K and Lichtman, A.H. Cellular and Molecular Immunology. Fifth Edition. Elsevier Saunders. Philadelphia. 2005

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