FAS gene mutation in a case of autoimmune lymphoproliferative syndrome type IA with accumulation of γδ+ T cells

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 I 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 up 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. RTPCR 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.