FAS and FASL expression in autoimmune lymphoproliferative syndrome and immune thrombocytopenia: limited diagnostic utility as transcriptional biomarkers

BACKGROUND: Autoimmune lymphoproliferative syndrome (ALPS) is an immune dysregulation disorder caused by defective lymphocyte apoptosis, most commonly involving the FAS-FAS ligand pathway. Because ALPS frequently presents with autoimmune cytopenias, particularly immune thrombocytopenia (ITP), its diagnosis may be challenging. This study evaluated whether FAS and FAS ligand gene expression could distinguish ALPS from ITP. METHODS: FAS and FAS ligand messenger RNA expression was measured by quantitative real-time polymerase chain reaction in whole-blood samples from patients with pediatric-onset ALPS (n = 24), patients with chronic ITP (n = 27), and healthy controls (n = 22). Expression levels were compared among groups, and their diagnostic performance was assessed using receiver operating characteristic curve analysis. RESULTS: FAS expression was significantly higher in patients with ALPS than in healthy controls (p < 0.01), but no significant difference was observed between ALPS and ITP. FAS expression showed moderate discrimination between ALPS and healthy controls but poor discrimination between ALPS and ITP. FAS ligand expression did not differ significantly among groups and showed no meaningful diagnostic performance. Neither FAS nor FAS ligand expression correlated with double-negative T-cell percentages or differed according to treatment status in patients with ALPS. CONCLUSIONS: FAS and FAS ligand transcriptional levels do not provide disease-specific discrimination between ALPS and ITP. These findings support the continued use of clinical, immunophenotypic, functional, and genetic investigations for the diagnosis of ALPS.