|Classification and external resources|
Lymphoproliferative disorders (LPDs) refer to several conditions in which lymphocytes are produced in excessive quantities. 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
- follicular lymphoma
- chronic lymphocytic leukemia
- acute lymphoblastic leukemia
- hairy cell leukemia
- multiple myeloma
- Waldenstrom's macroglobulinemia
- Wiskott-Aldrich syndrome
- post-transplant lymphoproliferative disorder
- Autoimmune lymphoproliferative syndrome (ALPS)
- "Lymphoid interstitial pneumonia"
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 pluripotent hematopoetic stem cells in the bone marrow. Individuals who have some sort of immunodysfuction are susceptible to develop 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.
Autoimmune 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. This gene is member 6 of the TNF-receptor superfamily (TNFRSF6). 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. 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.
Other inherited causes
Boys with X-linked immunodeficiency syndrome are at a higher risk of mortality associated with Epstein-Barr Virus 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.
Viral infection is a very common cause of lymphoproliferative disorders. In children, the most common is believed to be congenital HIV infection because it is highly associated with acquired immunodeficiency, which often leads to lymphoproliferative disorders.
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. The T cell variations are usually caused by the prolonged use of T cell suppressant drugs, such as sirolimus, tacrolimus or cyclosporine A.
- "Idiopathic Interstitial Pneumonias: Interstitial Lung Diseases: Merck Manual Professional". Retrieved 2008-12-09.
- Winter, S.S. Lymphoproliferative disorders. Emedicine. December 20, 2006. http://www.emedicine.com/ped/topic1345.htm. Accessed March 2007.
- 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.
- Abbas, A.K and Lichtman, A.H. Cellular and Molecular Immunology. Fifth Edition. Elsevier Saunders. Philadelphia. 2005