BCMA/CD19 CAR T cell therapy for refractory myasthenia gravis: Proteomic signatures and single-cell transcriptomics of disease flares
Science Advances, 2026
Huang X., Zhang Z., Liu D., Luo T., An X., Yang M., Li S., Wang G., Li H., Cao J., Sun Z., Du X., Wang Z., Guo X., Ma T., Peng D., Qi G., Zong S., Ding Y., Cui G., Shi M., Zheng J., Zhang Y.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases Immunotherapy | Pathophysiology | Serum |  Olink Target 96 |
Abstract
Myasthenia gravis (MG) is an autoimmune disorder characterized by B cell dysfunction. Here, we designed B cell maturation antigen (BCMA)/CD19 chimeric antigen receptor T cell (CAR T cell) therapy for six refractory MGs, demonstrating favorable safety with grade 1 cytokine release syndrome observed. CAR T cell expansion induced profound B cell depletion, a sustained reduction in acetylcholine receptor (AChR) antibody titers, and symptom improvement. Five patients achieved drug-free remission with minimal manifestations by month 6, persisting through the 12-month follow-up despite B cell reconstitution. Reconstituted B cells showed naïve predominance with diminished AChR specificity and functional capacities. Olink proteomics revealed up-regulation of anti-inflammatory factors, along with down-regulation of proinflammatory molecules. Single-cell sequencing revealed that age-associated B cells (ABCs) were up-regulated in a relapsed patient, and differential gene analysis indicated that Fc receptor-like 5 (FCRL5) expression was elevated in ABCs, whereas CAR T cell responders exhibited a down-regulated trend. Notably, similar ABC expansion and FCRL5 up-regulation occurred in rituximab-relapsed patients. Our findings support BCMA/CD19 CAR T cell therapy as feasible, tolerable, and effective in MG, identifying FCRL5 as a previously unidentified target in relapse.