Asurvey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation
(2011) Blood — Vol. 118, n° 18, p. 4798-4807 (2011)
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- Abstract
- 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 longterm monitoring of ALPS patients. We also noted a significantly greater occurrence of disease-related symptoms in male than in female patients. © 2011 by The American Society of Hematology.
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Neven, B., Magerus-Chatinet, A., Florkin, B., Gobert, D., Lambotte, O., De Somer, L., Lanzarotti, N., Stolzenberg, M.-C., Bader-Meunier, B., Aladjidi, N., Chantrain, C., Bertrand, Y., Jeziorski, E., Leverger, G., Michel, G., Suarez, F., Oksenhendler, E., Hermine, O., Blanche, S., et al. (2011). Asurvey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation. Blood, 118(18), 4798-4807. https://doi.org/10.1182/blood-2011-04-347641 (Original work published 2011)