Single-cell profiling identifies two Sjögren’s immune subtypes distinguished by anti-SSA status

An observational study in Arthritis & Rheumatology examined peripheral immune cell states in Sjögren’s disease to identify biologic features potentially useful for patient stratification. Researchers performed single-cell RNA sequencing with surface protein profiling on 1.5 million peripheral blood mononuclear cells from 333 participants, comparing groups defined by Sjögren’s diagnosis and anti-SSA antibody status.

The analysis identified two immunologic endotypes. SSA-positive participants had a dominant, persistent type I interferon signature associated with altered immune cell composition. Transitional B cells showed altered developmental states, reduced B-cell receptor diversity, shorter complementarity-determining region 3 sequences, and increased predicted interactions with activated immune cells. These findings were consistent with disturbed early B-cell selection. In contrast, SSA-negative participants with Sjögren’s disease had limited transcriptional differences from symptomatic controls without Sjögren’s disease.

The authors interpret the findings as supporting a two-disease model and propose transitional B cells as potential biomarkers and therapeutic targets. However, these molecular associations do not establish distinct causal mechanisms or demonstrate treatment benefit. The available abstract does not provide subgroup sizes, quantitative effect estimates, or clinical outcome data; full text was unavailable for assessment.