Association of clinical-immunologic clusters and anti-RNP/Ro52 antibody profiles with prognostic trajectories in primary Sjögren's disease.

OBJECTIVE

To delineate the prognostic architecture of primary Sjögren's disease (pSjD) through an integrated analysis of clinical-immunologic clusters and anti-RNP/anti-Ro52 antibody profiles.

METHODS

This ambispective cohort study enrolled 1293 patients with pSjD from China-Japan Friendship Hospital (2013-2023). Unsupervised hierarchical clustering was performed using 13 immunologic and demographic features. Patients were followed for a median of 4.5 years for six pre-specified endpoints including all-cause mortality, incident interstitial lung disease (ILD), and incident malignancy. Cluster-level and antibody-level prognostic associations were evaluated using Fine-Gray competing-risk and Cox regression models with multiply imputed estimates.

RESULTS

Four phenotypic clusters were identified among the 1293 patients, each with distinct prognostic trajectories for mortality, ILD, and malignancy. Cluster membership and antibody status captured non-redundant prognostic information. Anti-RNP positivity was independently associated with incident ILD (adjusted subdistribution hazard ratio [SHR] 2.64, 95% CI 1.07-6.48) and, in a propensity score-matched analysis (85 pairs), with lower all-cause mortality (HR 0.25, 95% CI 0.07-0.89). Anti-Ro52 positivity was the most consistent predictor of incident hematologic involvement (adjusted SHR 1.54, 95% CI 1.12-2.11). Both antibodies were independently associated with incident malignancy, and double-positive patients exhibited an approximately sixfold increased risk compared with double-negative patients (adjusted SHR 6.05, 95% CI 1.93-18.94).

CONCLUSION

Immunophenotypic clustering and autoantibody profiling jointly stratify long-term outcomes in this single-center pSjD cohort. Dual anti-RNP and anti-Ro52 positivity identifies a small subgroup with an elevated risk of malignancy; these findings require independent validation before informing clinical surveillance strategies.