Effectiveness of sirolimus in a patient with a novel heterozygous FAS mutation leading to  severe autoimmune lymphoproliferative syndrome

Abstract Here we report a patient with a novel mutation in the FAS gene associated with a severe phenotype of the autoimmune lymphoproliferative syndrome. FAS gene identified as a novel spontaneous somatic heterozygous missense mutation (c.857G > A, p.G286E) in exon 9, causing an amino acid exchange was identified using sequencing. Consequently, the treatment with sirolimus (1mg/d, blood concentration 5-15ng/L) was initiated. Subsequently, the patient’s platelet count and clinical condition improved rapidly. Moreover, our in vitro data showed that G286E could inhibit cell proliferation and induce apoptosis compared with the wild type. To sum up, these data indicated that defective apoptosis might contribute to the clinical phenotype of lymphoproliferation in FAS deficient patients. The polarization of DNT/Treg axis may be an operative target of the sirolimus application.