A novel cell type negatively associated with secondary autoimmunity in alemtuzumab-treated patients is revealed through single-cell longitudinal analysis of clinical trial samples

Abstract

Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is an approved treatment for relapsing forms of multiple sclerosis (RMS). While its efficacy has been demonstrated in clinical studies, its use is associated with unpredictable non-MS autoimmunity manifesting months or years after treatment. Approximately 40% of treated patients present with autoimmune thyroid events, 2% with platelet deficiency (immune thrombocytopenia; ITP), and 0.34% with autoimmune nephropathies. The lack of predictive biomarkers necessitates careful monitoring in clinical practice with a Risk Management Plan or Risk Evaluation and Mitigation Strategy (RMP/REMS) in place for early detection of these autoimmune events. We carried out a longitudinal single-cell analysis of PBMCs in a small subset of alemtuzumab-treated patients from the phase 3 CARE-MS I (CAMMS323) study3 and identified a novel platelet lineage cell negatively associated with thyroid autoimmunity. This discovery raises the possibility that a shared underlying mechanism may contribute to the incidence of thyroid autoimmunity and ITP in alemtuzumab-treated patients.