Despite the limitation of the small number of patients, the retrospective nature of our work and the lack of histological evaluations of lymphoid tissue, we identified a subgroup of patient with ALPS-FAS with unexpected CD4 lymphopenia caused by anti-lymphocyte autoantibodies mediating ADCC of CD4 T-cells and associated with the expansion of a specific subset of cTfh (CXCR5+CCR7lowPD-1high) already linked to autoantibody production in other clinical contexts. Here, CXCR5 is linked to autoimmune lymphoproliferative syndrome.