This study investigated the role of age-associated B cells (ABCs) in Takayasu's arteritis (TAK) pathogenesis — including their activation pathway, proinflammatory functions, and response to tofacitinib vs. adalimumab — using histology, bulk RNA-seq, scRNA-seq, flow cytometry, and in vitro experiments, with a small exploratory clinical follow-up (n=4).
ABCs in TAK drive inflammation via proinflammatory cytokine production and Th17 promotion, largely independent of antibody-secreting cell differentiation — a pattern distinct from SLE. In vitro, tofacitinib reduced ABC proportions and attenuated their proinflammatory phenotype more effectively than adalimumab (n=15), with consistent trends in 4 clinical cases.
The exploratory clinical cohort comparing tofacitinib to adalimumab was very small (n=4), limiting generalizability. The study is largely mechanistic and observational, without a randomized comparator arm. Histological analysis was restricted to 5 patients.
In TAK, B cells appear to promote inflammation through antibody-independent mechanisms, suggesting that standard anti-TNF therapy may be insufficient to fully suppress this pathway. JAK inhibition with tofacitinib shows early promise in targeting ABCs, warranting prospective trials in TAK.
