Presentation (CTI)

OBJECTIVES: Sjögren’s disease (SjD) is a heterogeneous systemic autoimmune disease with phenotype ranging from dryness to life-threatening complications. Biomarkers may help identify patients at increased risk of severe systemic complications and support earlier risk stratification. This study aimed to synthesize evidence on associations between biomarkers and major systemic complications in SjD.
METHODS: A systematic literature review of published evidence was conducted in accordance with NICE and PRISMA guidelines. Published studies (January 2012-February 2026) reporting associations between serological markers and systemic outcomes (lymphoma, interstitial lung disease [ILD], cardiovascular [CV], neurological, and renal involvement) were identified through database, conference (2022-2025), and bibliographic searches.
RESULTS: Multiple biomarkers were associated with increased systemic risk. Cryoglobulinemia showed strong and consistent associations with lymphoma (OR 3.68-16.9; HR 11.07), CV risk (OR 10.13), and kidney involvement (OR 2.97-6.45). Hypocomplementemia was also associated with lymphoma (OR 1.2-13.9; HR 1.42), CV manifestations (OR 1.32) and cryoglobulinemic vasculitis (RR 24), and kidney involvement (OR 2.09-3.19). Rheumatoid factor positivity was associated with lymphoma (OR 3.04; HR 1.04), subclinical atherosclerosis (OR 11.96), neurological involvement (PNS OR 1.15), and renal disease (OR 3.11). Anti-Ro/SSA positivity was associated with hypertension (OR 3.839), CV disease (OR 2.1), and kidney involvement (OR 1.51-3.42; HR 3.21), although associations with lymphoma and ILD were inconsistent. Anti-La/SSB positivity was associated with ILD (OR 3.62), pulmonary arterial hypertension (OR 4.095), neurological involvement (OR 1.8), and kidney involvement (OR 1.8-2.35; HR 1.53). Additional markers, including lymphopenia, thrombocytopenia, elevated CRP/ESR, hypergammaglobulinemia/IgG abnormalities, hypoalbuminemia, and BAFF, were associated with selected complications.
CONCLUSIONS: In SjD, biomarkers appear to be informative indicators of systemic complication risk. Cryoglobulinemia, hypocomplementemia, rheumatoid factor positivity, and SSA/SSB seropositivity may support earlier identification of patients at higher risk of lymphoma, ILD, CV, neurological, and renal complications, with potential relevance for risk-stratified management and future evidence-based decision-making.