X-linked lymphoproliferative disease: Difference between revisions
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Strangely, in boys with X-linked lymphoproliferative disorder there is an overwhelming T-cell mediated response to the [[Epstein-Barr virus]] (EBV), which often leads to death from bone marrow failure, irreversible hepatitis, and malignant lymphoma. However, the connection between EBV and X-linked lymphoproliferative disorder is yet to be determined.<ref name="item14">Winter, S.S. Lymphoproliferative disorders. Emedicine. December 20, 2006. http://www.emedicine.com/ped/topic1345.htm. Accessed March 2007.</ref> |
Strangely, in boys with X-linked lymphoproliferative disorder there is an overwhelming T-cell mediated response to the [[Epstein-Barr virus]] (EBV), which often leads to death from bone marrow failure, irreversible hepatitis, and malignant lymphoma. However, the connection between EBV and X-linked lymphoproliferative disorder is yet to be determined.<ref name="item14">Winter, S.S. Lymphoproliferative disorders. Emedicine. December 20, 2006. http://www.emedicine.com/ped/topic1345.htm. Accessed March 2007.</ref> |
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Patients produce insufficient numbers of [[CD27]] [[memory B cell]]s.<ref name="pmid16424938">{{cite journal |author=Ma CS, Pittaluga S, Avery DT, ''et al'' |title=Selective generation of functional somatically mutated IgM+CD27+, but not Ig isotype-switched, memory B cells in X-linked lymphoproliferative disease |journal=J. Clin. Invest. |volume=116 |issue=2 |pages=322–33 |year=2006 |month=February |pmid=16424938 |pmc=1332028 |doi=10.1172/JCI25720 |url=http://dx.doi.org/10.1172/JCI25720}}</ref> |
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==References== |
==References== |
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Revision as of 19:08, 17 September 2008
| X-linked lymphoproliferative disease | |
|---|---|
| Specialty | Hematology  |
X-linked lymphoproliferative disease is a lymphoproliferative disorder.
Causes
There is a mutation on the X chromosome that has been found to be associated with a T and NK cell lymphoproliferative disorder. The mutation is on the long arm of the chromosome, at position 25, which is denoted as Xq25. At this position, there is a deletion in the SH2D1A gene, which codes for an SH2 domain on a signal transducing protein called SLAM-associated protein (SAP).
The term SH2 domain stands for src-homology 2 domain, which is a three-dimensional domain structure of about 100 amino acid residues. These domains are present in many signaling proteins because they permit specific, non-covalent bonding to proteins that contain phosphotyrosines. The amino acid residues adjacent to the phosphotyrosine on the target protein are what determine the unique binding specificity.[1]
The SAP protein is important in the signaling events that activate T and NK cells[2] because it functions as an intracellular adapter that transduces T and NK cell activation. Normally, the SAP protein is expressed in the cytoplasm of T and NK cells, where it binds to the cytoplasmic domain of the surface receptor called Signaling Lymphocyte Activation Molecule (SLAM). This binding initiates a signal transduction pathway, which results in the modulation of IFN-γ. A deletion in the SH2D1A gene leads to a non-functional SH2 domain on the SAP protein, which means it is unable to bind to the SLAM molecule, leading to a lack of modulation of IFN-γ, causing uncontrolled cell proliferation.
Presentation
Strangely, in boys with X-linked lymphoproliferative disorder there is an overwhelming T-cell mediated response to the Epstein-Barr virus (EBV), which often leads to death from bone marrow failure, irreversible hepatitis, and malignant lymphoma. However, the connection between EBV and X-linked lymphoproliferative disorder is yet to be determined.[3]
Patients produce insufficient numbers of CD27 memory B cells.[4]
References
- ^ Abbas, A.K and Lichtman, A.H. Cellular and Molecular Immunology. Fifth Edition. Elsevier Saunders. Philadelphia. 2005
- ^ "X-linked Lymphoproliferative Syndrome: Immunodeficiency Disorders: Merck Manual Professional". Retrieved 2008-03-01.
- ^ Winter, S.S. Lymphoproliferative disorders. Emedicine. December 20, 2006. http://www.emedicine.com/ped/topic1345.htm. Accessed March 2007.
- ^ Ma CS, Pittaluga S, Avery DT; et al. (2006). "Selective generation of functional somatically mutated IgM+CD27+, but not Ig isotype-switched, memory B cells in X-linked lymphoproliferative disease". J. Clin. Invest. 116 (2): 322–33. doi:10.1172/JCI25720. PMC 1332028. PMID 16424938.
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