Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations

作者：Price Susan; Shaw Pamela A; Seitz Amy; Joshi Gyan; Davis Joie; Niemela Julie E; Perkins Katie; Hornung Ronald L; Folio Les; Rosenberg Philip S; Puck Jennifer M; Hsu Amy P; Lo Bernice; Pittaluga Stefania; Jaffe Elaine S; Fleisher Thomas A; Rao V Koneti^*; Lenardo Michael J

来源：Blood, 2014, 123(13): 1989-1999.

DOI：10.1182/blood-2013-10-535393

Autoimmune lymphoproliferative syndrome (ALPS) presents in childhood with nonmalignant lymphadenopathy and splenomegaly associated with a characteristic expansion of mature CD4 and CD8 negative or double negative T-cell receptor alpha beta(+) T lymphocytes. Patients often present with chronic multilineage cytopenias due to autoimmune peripheral destruction and/or splenic sequestration of blood cells and have an increased risk of B-cell lymphoma. Deleterious heterozygous mutations in the FAS gene are the most common cause of this condition, which is termed ALPS-FAS. We report the natural history and pathophysiology of 150 ALPS-FAS patients and 63 healthy mutation-positive relatives evaluated in our institution over the last 2 decades. Our principal findings are that FAS mutations have a clinical penetrance of <60%, elevated serum vitamin B-12 is a reliable and accurate biomarker of ALPS-FAS, and the major causes of morbidity and mortality in these patients are the overwhelming postsplenectomy sepsis and development of lymphoma. With longer follow-up, we observed a significantly greater relative risk of lymphoma than previously reported. Avoiding splenectomy while controlling hypersplenism by using corticosteroid-sparing treatments improves the outcome in ALPS-FAS patients.

• 出版日期2014-3-27