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)1, and 0.34% with autoimmune nephropathies2. 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. HighlightsO_LIA novel platelet-lineage cell type present in peripheral blood is uncovered and characterized C_LIO_LIDepletion and/or transcriptomic changes in this cell type are associated with increased incidence of secondary autoimmunity in MS patients on Alemtuzumab. C_LIO_LIRetrospective single-cell analysis studies can uncover novel insights and lead to future biomarker development C_LI

https://www.medrxiv.org/content/medrxiv/early/2021/06/28/2021.06.21.21258814.full.pdf

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

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