title: FAS gene mutation in a case of autoimmune lymphoproliferative syndrome type IA with accumulation of gammadelta+ T cells.
abstract: A 6-month-old girl presented to the hospital with cervical lymphadenopathy and hepatosplenomegaly. She was known to have an enlarged spleen, anemia, and thrombocytopenia since the age of 1 month. A lymph node biopsy showed a diffuse proliferation of blasts with few remnants of follicles. The blasts were CD3+CD57+CD4-CD8-, consistent with the usual autoimmune lymphoproliferative syndrome phenotype. However, these double negative T cells stained positive for gammadelta T-cell receptors, whereas double negative T cells in patients with autoimmune lymphoproliferative syndrome usually bear alphabeta T-cell receptor. Mutation analysis of the FAS gene revealed a mutation in the death domain of the FAS gene, which is a frequent finding in patients with autoimmune lymphoproliferative syndrome. Based on these results, the diagnosis of autoimmune lymphoproliferative syndrome was established. RT-PCR analysis of the affected lymph node tissue revealed a strong upregulation of interleukin 10 and a moderate upregulation of interferon-gamma expression compared with normal tissue. Our findings indicate that autoimmune lymphoproliferative syndrome can result in a prominent proliferation of gammadelta+ double negative T cells. It is important to distinguish this benign polyclonal proliferation from neoplastic gammadelta+ T-cell proliferations, such as hepatosplenic gammadelta T-cell lymphomas. Factors contributing to the accumulation of these gammadelta+ double negative T cells may be an unidentified infection in combination with the young age of onset in this patient.
authors.affiliation: Department of Pathology and Laboratory Medicine, PO Box 30.001, 9700 RB Groningen, The Netherlands. a.van.den.berg@path.azg.nl
authors.forename: Anke
authors.initials: A
authors.lastname: van den Berg
authors.forename: Rienk
authors.initials: R
authors.lastname: Tamminga
authors.forename: Debora
authors.initials: D
authors.lastname: de Jong
authors.forename: Ewerton
authors.initials: E
authors.lastname: Maggio
authors.forename: Willem
authors.initials: W
authors.lastname: Kamps
authors.forename: Sibrand
authors.initials: S
authors.lastname: Poppema
mesh_terms: D001327:Autoimmune Diseases / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D009154:Mutation; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000235:genetics*
chemical_list: D019014:fas Receptor