This ancillary analysis of the ASSET trial examined whether abatacept modulates CD319+/SLAMF7+ cytotoxic T cells in 67 participants with systemic sclerosis (SSc), comparing immune changes between abatacept and placebo groups at baseline and months 1, 3, and 6, with sub-analysis by molecular endotype (fibroproliferative vs. other).
Abatacept reduced CD4+CD319+ and CD8+CD319+ T cell frequencies by month 6 (placebo did not); effects were strongest in fibroproliferative patients (CD8+CD319+ decrease vs. placebo: n=7 vs. n=36, p=0.0377). Reduction in CD4+CD319+ T cells correlated with mRSS improvement (r=0.5297, p=0.0423), and IL-17A in CD8+CD319+ T cells dropped significantly at month 6 (p=0.0004) in this endotype.
- Fibroproliferative subgroup was small (n=7 abatacept vs. n=36 placebo), limiting the power and generalizability of endotype-specific findings. - Ancillary/post-hoc design means findings are exploratory and hypothesis-generating rather than confirmatory. - Skin scRNA-seq included only 5 healthy controls and 8 SSc patients, restricting depth of tissue-level conclusions.
In SSc, particularly the fibroproliferative subtype, abatacept appears to selectively suppress CD319+ cytotoxic T cells and pro-fibrotic cytokines (IL-4, IL-17A), with T cell reduction tracking clinical skin improvement. Clinicians should consider molecular endotyping when evaluating abatacept response in SSc patients.
