Affiliation:
1. Department of Microbiology, Infectiology and Immunology Université de Montréal Montréal Québec Canada
2. Department of Pediatrics, Faculty of Medicine Université de Montréal Montréal Québec Canada
Abstract
AbstractBackgroundAutoimmune lymphoproliferative syndrome (ALPS) is a rare primary immune disorder caused by defect of the extrinsic apoptotic pathway. The current diagnostic criteria combine clinical features and typical biomarkers but have not been the object of clear international consensus.MethodsWe conducted a retrospective study on pediatric patients who were investigated for autoimmune cytopenia and/or lymphoproliferation at the CHU Sainte‐Justine Hospital over 10 years. Patients were screened using the combination of TCRαβ+ CD4− CD8− “double negative” (DN) T cells and soluble plasmatic FAS ligand (sFASL).ResultsAmong the 398 tested patients, the median sFASL and DN T cells were 200 ng/mL and 1.8% of TCRαβ+ T cells, respectively. sFASL was highly correlated with vitamin B12 levels. We identified five patients diagnosed with ALPS for whose sFASL and vitamin B12 levels were the more discriminating biomarkers. While ALPS diagnostic criteria had high sensibility, their predictive value remained low.ConclusionsFASL level can efficiently discriminate patients with ALPS when using the appropriate thresholds. Our study highlights the need for an international consensus to redefine the place and threshold of biological biomarkers for ALPS diagnosis.