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X-linked lymphoproliferative disease
Classification and external resources
ICD-10 D82.3
OMIM 308240
DiseasesDB 3998
eMedicine med/1370
MeSH D008232

X-linked lymphoproliferative disease (also known as "Duncan's disease"[1]:86) is a lymphoproliferative disorder.[2]



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.[3]

The SAP protein is important in the signaling events that activate T and NK cells [4] 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.


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.[5]

Patients produce insufficient numbers of CD27 memory B cells.[6]


  1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.  
  2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 808. ISBN 1-4160-2999-0.  
  3. ^ Abbas, A.K and Lichtman, A.H. Cellular and Molecular Immunology. Fifth Edition. Elsevier Saunders. Philadelphia. 2005
  4. ^ "X-linked Lymphoproliferative Syndrome: Immunodeficiency Disorders: Merck Manual Professional". Retrieved 2008-03-01.  
  5. ^ Winter, S.S. Lymphoproliferative disorders. Emedicine. December 20, 2006. Accessed March 2007.
  6. ^ Ma CS, Pittaluga S, Avery DT, et al. (February 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. PMID 16424938.  

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