Autoimmune lymphoproliferative syndrome caused by a homozygous null FAS ligand (FASLG) mutation

作者：Magerus Chatinet Aude^*; Stolzenberg Marie Claude; Lanzarotti Nina; Neven Benedicte; Daussy Cecile; Picard Capucine; Neveux Nathalie; Desai Mukesh; Rao Meghana; Ghosh Kanjaksha; Madkaikar Manisha; Fischer Alain; Rieux Laucat Frederic

来源：Journal of Allergy and Clinical Immunology, 2013, 131(2): 486-490.

DOI：10.1016/j.jaci.2012.06.011

• Autoimmune lymphoproliferative syndrome
• Fas ligand
• diagnosis

Background: Autoimmune lymphoproliferative syndrome (ALPS) is characterized by chronic nonmalignant lymphoproliferation, accumulation of double-negative T cells, hypergammaglobulinemia G and A, and autoimmune cytopenia. %26lt;br%26gt;Objectives: Although mostly associated with FAS mutations, different genetic defects leading to impaired apoptosis have been described in patients with ALPS, including the FAS ligand gene (FASLG) in rare cases. Here we report on the first case of complete FAS ligand deficiency caused by a homozygous null mutant. %26lt;br%26gt;Methods: Double-negative T-cell counts and plasma IL-10 and FAS ligand concentrations were determined as ALPS markers. The FASLG gene was sequenced, and its expression was analyzed by means of Western blotting. FAS ligand function was assessed based on reactivation-induced cell death. %26lt;br%26gt;Results: We describe a patient born to consanguineous parents who presented with a severe form of ALPS caused by FASLG deficiency. Although the clinical presentation was compatible with a homozygous FAS mutation, FAS-induced apoptosis was normal, and plasma FAS ligand levels were not detectable. This patient carries a homozygous, germline, single-base-pair deletion in FASLG exon 1, leading to a premature stop codon (F87fs x95) and a complete defect in FASLG expression. The healthy parents were each heterozygous for the mutation, confirming its recessive trait. %26lt;br%26gt;Conclusion: FAS ligand deficiency should be screened in patients presenting with ALPS features but lacking the usual markers, including plasma soluble FAS ligand and an in vitro apoptotic defect. An activation-induced cell death test could help in discrimination. (J Allergy Clin Immunol 2013;131:486-90.)

• 出版日期2013-2