A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation

作者：Neven Benedicte^*; Magerus Chatinet Aude; Florkin Benoit; Gobert Delphine; Lambotte Olivier; De Somer Lien; Lanzarotti Nina; Stolzenberg Marie Claude; Bader Meunier Brigitte; Aladjidi Nathalie; Chantrain Christophe; Bertrand Yves; Jeziorski Eric; Leverger Guy; Michel Gerard; Suarez Felipe; Oksenhendler Eric; Hermine Olivier; Blanche Stephane; Picard Capucine; Fischer Alain; Rieux Laucat Frederic

来源：Blood, 2011, 118(18): 4798-4807.

DOI：10.1182/blood-2011-04-347641

Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disorder characterized by early-onset, chronic, nonmalignant lymphoproliferation, autoimmune manifestations, and susceptibility to lymphoma. The majority of ALPS patients carry heterozygous germline (ALPS-FAS) or somatic mutations (ALPS-sFAS) of the TNFRSF6 gene coding for FAS. Although the clinical features of ALPS have been described previously, long-term follow-up data on morbidity and mortality are scarce. We performed a retrospective analysis of clinical and genetic features of 90 ALPS-FAS and ALPS-sFAS patients monitored over a median period of 20.5 years. Heterozygous germline mutations of TNFRSF6 were identified in 83% of probands. Somatic TNFRSF6 mutations were found in 17% of index cases (all located within the intracellular domain of FAS). Sixty percent of the ALPS-FAS patients with mutations in the extracellular domain had a somatic mutation affecting the second allele of TNFRSF6; age at onset was later in these patients. No other genotype-phenotype correlations could be found. Long-term analysis confirmed a trend toward spontaneous remission of lymphoproliferation in adulthood but mixed outcomes for autoimmune manifestations. We observed significant and potentially life-threatening disease and treatment-related morbidity, including a high risk of sepsis after splenectomy that calls for careful long-term monitoring of ALPS patients. We also noted a significantly greater occurrence of disease-related symptoms in male than in female patients. (Blood. 2011;118(18):4798-4807)

• 出版日期2011-11-3