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Article Dans Une Revue Blood Année : 2011

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

Bénédicte Neven
  • Fonction : Auteur
Aude Magerus-Chatinet
  • Fonction : Auteur
Benoit Florkin
  • Fonction : Auteur
Delphine Gobert
  • Fonction : Auteur
Olivier Lambotte
  • Fonction : Auteur
Lien de Somer
  • Fonction : Auteur
Nina Lanzarotti
  • Fonction : Auteur
Marie-Claude Stolzenberg
  • Fonction : Auteur
Brigitte Bader-Meunier
  • Fonction : Auteur
Nathalie Aladjidi
  • Fonction : Auteur
Christophe Chantrain
  • Fonction : Auteur
Yves Bertrand
  • Fonction : Auteur
Eric Jeziorski
  • Fonction : Auteur
Guy Leverger
  • Fonction : Auteur
Gérard Michel
  • Fonction : Auteur
Felipe Suarez
  • Fonction : Auteur
Eric Oksenhendler
  • Fonction : Auteur
Olivier Hermine
  • Fonction : Auteur
Stéphane Blanche
  • Fonction : Auteur
Capucine Picard
  • Fonction : Auteur
Alain Fischer
  • Fonction : Auteur

Résumé

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 long-term monitoring of ALPS patients. We also noted a significantly greater occurrence of disease-related symptoms in male than in female patients.

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Dates et versions

hal-04457098 , version 1 (14-02-2024)

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Bénédicte Neven, Aude Magerus-Chatinet, Benoit Florkin, Delphine Gobert, Olivier Lambotte, et al.. A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation. Blood, 2011, 118 (18), pp.4798-4807. ⟨10.1182/blood-2011-04-347641⟩. ⟨hal-04457098⟩

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