Open Access Articles- Top Results for X-linked lymphoproliferative disease

X-linked lymphoproliferative disease

X-linked lymphoproliferative disease
Classification and external resources
ICD-10 D82.3
OMIM 308240 300635
DiseasesDB 3998
eMedicine med/1370
NCI X-linked lymphoproliferative disease
Patient UK X-linked lymphoproliferative disease
MeSH D008232

X-linked lymphoproliferative disease (also known as "Duncan's disease"[1]:86 or "Purtilo syndrome"[2]) is a lymphoproliferative disorder.[3]



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 signalling 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.[4]

The SAP protein is important in the signalling events that activate T- and NK-cells[5] due to its adaptor function. 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, making it unable to bind to SLAM. This leads to aberrant IFN-γ modulation, causing uncontrolled cell proliferation.


A second form is associated with XIAP.[6]

Some sources recommend classifying this condition as "X-linked familial hemophagocytic lymphohistiocytosis" instead of X-linked lymphoproliferative disease.[7]


Strangely, in boys with X-linked lymphoproliferative disorder, there is an inability to mount an immune response to the Epstein-Barr virus (EBV),[8] 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.[9]

Patients produce insufficient numbers of CD27 memory B cells.[10]


  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. ^
  3. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 808. ISBN 1-4160-2999-0. 
  4. ^ Abbas, A.K; Lichtman, A.H. (2005). Cellular and Molecular Immunology (5th ed.). Philadelphia: Elsevier Saunders. 
  5. ^ X-linked Lymphoproliferative Syndrome at Merck Manual of Diagnosis and Therapy Professional Edition
  6. ^ Rigaud S, Fondanèche MC, Lambert N et al. (November 2006). "XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome". Nature 444 (7115): 110–4. PMID 17080092. doi:10.1038/nature05257. 
  7. ^ Marsh RA, Madden L, Kitchen BJ et al. (August 2010). "XIAP deficiency: a unique primary immunodeficiency best classified as X-linked familial hemophagocytic lymphohistiocytosis and not as X-linked lymphoproliferative disease". Blood 116 (7): 1079–82. PMC 2938130. PMID 20489057. doi:10.1182/blood-2010-01-256099. 
  8. ^ Kumar,Vinay; Cotran, Ramzi S.; Robbins, Stanley L. (2003). Robbins Basic Pathology, 7th Edition. Philadelphia: Elsevier. p. 418. ISBN 1-4160-2534-0. 
  9. ^ Lymphoproliferative Disorders at eMedicine
  10. ^ 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. PMC 1332028. PMID 16424938. doi:10.1172/JCI25720. 

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