- X-linked lymphoproliferative disease
-
X-linked lymphoproliferative disease Classification and external resources ICD-10 D82.3 OMIM 308240 300635 DiseasesDB 3998 eMedicine med/1370 MeSH D008232 X-linked lymphoproliferative disease (also known as "Duncan's disease"[1]:86 or "Purtilo syndrome"[2]) is a lymphoproliferative disorder.[3]
Contents
Causes
XLP1
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] 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.
XLP2
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]
Presentation
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]
References
- ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
- ^ http://ghr.nlm.nih.gov/condition/x-linked-lymphoproliferative-disease
- ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 808. ISBN 1-4160-2999-0.
- ^ 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". http://www.merck.com/mmpe/sec13/ch164/ch164p.html. Retrieved 2008-03-01.
- ^ 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. doi:10.1038/nature05257. PMID 17080092.
- ^ 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. doi:10.1182/blood-2010-01-256099. PMC 2938130. PMID 20489057. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2938130.
- ^ Kumar,Vinay; Cotran, Ramzi S.; Robbins, Stanley L. (2003). Robbins Basic Pathology, 7th Edition. Philadelphia: Elsevier. pp. 418. ISBN 1-4160-2534-0.
- ^ 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. (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. PMC 1332028. PMID 16424938. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1332028.
External links
- X-linked lymphoproliferative disease community
- XLP Research Trust
- GeneReview/NIH/UW entry on Lymphoproliferative Disease, X-Linked
Hematological malignancy/leukemia histology (ICD-O 9590–9989, C81–C96, 200–208)
Lymphoid/Lymphoproliferative, Lymphomas/Lymphoid leukemias (9590–9739, 9800–9839)By development/
markerALL (Precursor B acute lymphoblastic leukemia/lymphoma)CD5+CD22+germinal center/follicular B cell (Follicular, Burkitt's, GCB DLBCL, Primary cutaneous follicular lymphoma)marginal zone/marginal-zone B cell (Splenic marginal zone, MALT, Nodal marginal zone, Primary cutaneous marginal zone lymphoma)see immunoproliferative immunoglobulin disordersBy infectionDiffuse large B-cell lymphoma · Intravascular large B-cell lymphoma · Primary cutaneous marginal zone lymphoma · Primary cutaneous immunocytoma · Plasmacytoma · Plasmacytosis · Primary cutaneous follicular lymphomaBy development/
markerTdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma)
prolymphocyte (Prolymphocytic)
CD30+ (Anaplastic large-cell lymphoma, Lymphomatoid papulosis type A)indolent: Mycosis fungoides · Pagetoid reticulosis · Granulomatous slack skin
aggressive: Sézary's disease · Adult T-cell leukemia/lymphomaNon-MFCD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma · Pleomorphic T-cell lymphoma · Lymphomatoid papulosis type B
CD30+: CD30+ cutaneous T-cell lymphoma · Secondary cutaneous CD30+ large cell lymphoma · Lymphomatoid papulosis type AOther peripheralHepatosplenic · Angioimmunoblastic · Enteropathy-associated T-cell lymphoma · Peripheral T-cell lymphoma-Not-Otherwise-Specified (Lennert lymphoma) · Subcutaneous T-cell lymphomaBy infectionHTLV-1 (Adult T-cell leukemia/lymphoma)NK cell/
(most CD56)Aggressive NK-cell leukemia · Blastic NK cell lymphomaT or NKLymphoid+myeloidLymphoproliferative disorders (X-linked lymphoproliferative disease, Autoimmune lymphoproliferative syndrome) · Leukemoid reaction · Diffuse infiltrative lymphocytosis syndromeCutaneous lymphoid hyperplasia Cutaneous lymphoid hyperplasia with bandlike and perivascular patterns · Cutaneous lymphoid hyperplasia with nodular pattern · Jessner lymphocytic infiltrate of the skinDeficiencies of intracellular signaling peptides and proteins GTP-binding protein regulators GTPase-activating proteinMarinesco–Sjögren syndrome · Aarskog–Scott syndrome · Juvenile primary lateral sclerosis · X-Linked mental retardation 1G protein cAMP/GNAS1: Pseudopseudohypoparathyroidism · Progressive osseous heteroplasia · Pseudohypoparathyroidism · Albright's hereditary osteodystrophy · McCune–Albright syndrome
CGL 2RAS: HRAS (Costello syndrome) · KRAS (Noonan syndrome 3, KRAS Cardiofaciocutaneous syndrome)
RAB: RAB7 (Charcot–Marie–Tooth disease) · RAB23 (Carpenter syndrome) · RAB27 (Griscelli syndrome type 2)
RHO: RAC2 (Neutrophil immunodeficiency syndrome)
ARF: SAR1B (Chylomicron retention disease) ARL13B (Joubert syndrome 8) · ARL6 (Bardet–Biedl syndrome 3)MAP kinase Other kinase/phosphatase RPS6KA3 (Coffin-Lowry syndrome) · CHEK2 (Li-Fraumeni syndrome 2) · IKBKG (Incontinentia pigmenti) · STK11 (Peutz–Jeghers syndrome) · DMPK (Myotonic dystrophy 1) · ATR (Seckel syndrome 1) · GRK1 (Oguchi disease 2) · WNK4/WNK1 (Pseudohypoaldosteronism 2)PTEN (Bannayan–Riley–Ruvalcaba syndrome, Lhermitte–Duclos disease, Cowden syndrome, Proteus-like syndrome) · MTM1 (X-linked myotubular myopathy) · PTPN11 (Noonan syndrome 1, LEOPARD syndrome, Metachondromatosis)Signal transducing adaptor proteins Other NF2 (Neurofibromatosis type II) · NOTCH3 (CADASIL) · PRKAR1A (Carney complex) · PRKAG2 (Wolff–Parkinson–White syndrome) · PRKCSH (PRKCSH Polycystic liver disease) · XIAP (XIAP2)Categories:- Noninfectious immunodeficiency-related cutaneous conditions
- Diseases of immune dysregulaton
Wikimedia Foundation. 2010.
