#4-80E. Unraveling Sjögren’s Disease Progression: The Shift from Interferon to Proliferative Pathways (Arthritis Rheumatol, 2026)

How can we accurately predict and intercept disease progression in a highly heterogeneous condition like Sjögren’s disease? This study analyzed blood transcriptomic data from the ASSESS cohort to characterize the molecular pathology across three distinct clinical clusters: B-cell active with low symptoms (BALS), high systemic activity (HSA), and low systemic activity with high symptoms. The researchers discovered robust type I and II interferon (IFN) signatures in both the BALS and HSA groups. The most groundbreaking clinical finding suggests a multi-step model of disease progression; early severe progression in the BALS cluster is driven by hyperactive IFN and inflammatory signaling, which subsequently shifts toward cell proliferative and metabolic pathways, such as mTOR and MYC, in the HSA cluster. However, when critically appraising this study, it is crucial to note that the transcriptomic profiling was conducted at a single baseline timepoint, meaning the causal relationships between these molecular shifts and clinical progression remain hypothetical without longitudinal validation. For clinicians, understanding this dynamic molecular shift is vital as it highlights the potential for stage-specific, personalized therapeutic interventions—such as targeting mTOR pathways in later stages—ultimately refining how we manage systemic complications in Sjögren’s disease.

Citation: Silva-Saffar SE, Nguyen Y, Seror R, Gottenberg JE, Niarakis A, Mariette X, Nocturne G. Distinct molecular pathways supporting Sjögren's Disease clusters and disease progression. Arthritis & Rheumatology. 2026. DOI: 10.1002/art.70251

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