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: Anke van den Berg, Rienk Tamminga, Debora de Jong, Ewerton Maggio, Willem Kamps, Sibrand Poppema
• Journal: The American journal of surgical pathology (Am J Surg Pathol) Vol. 27 Issue 4 Pg. 546-53 (Apr 2003) ISSN: 0147-5185 [Print] United States
• PMID: 12657942 (Publication Type: Case Reports, Journal Article)

Chemical References

• fas Receptor

Topics

• Autoimmune Diseases (genetics)
• Female
• Humans
• Infant
• Lymphoproliferative Disorders (genetics)
• Mutation
• T-Lymphocytes (immunology)
• fas Receptor (genetics)