[Pubmed] BCMA/CD19 CAR T cell therapy for refractory myasthenia gravis: Proteomic signatures and single-cell transcripto
Posté : 02 janv. 2026 12:00
Sci Adv. 2026 Jan 2;12(1):eaeb6424. doi: 10.1126/sciadv.aeb6424. Epub 2026 Jan 2.
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.
PMID:41481736 | DOI:10.1126/sciadv.aeb6424
Source: https://pubmed.ncbi.nlm.nih.gov/4148173 ... 22+67771e2