Distinct blood gene signatures predict non-response to B-cell therapy in Sjogren's

A phase II trial analysis (n=43) of rituximab, belimumab, and sequential belimumab-rituximab in active Sjogren's disease used whole-blood RNA sequencing to identify baseline markers of treatment response. The study reports that ESSDAI non-response was linked to a complement-regulated, cytotoxic and stromal-remodelling signature (higher TGFB2, C4A, CD8A, lower C4BPA; AUC 0.89), while STAR non-response was linked to a distinct IL-1/IL-18/FcgammaR-centred myeloid module (higher SPP1, TLR4, IL1R1, IL18R1, IL1RAP, TREM1, FCGR2A; AUC 0.80), with no overlap between the two gene sets. The authors state this complete non-overlap suggests B-cell-independent inflammatory circuits may drive non-response, pointing to complement, TGFB2, IL-1/IL-18 and FcgammaR pathways as possible targets beyond B-cell-targeted therapy.

Most relevant for: Adults with active Sjogren's disease being considered for or treated with anti-CD20 or BAFF/BlyS inhibitor therapy.

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