Distinct immunological features characterize early-onset primary Sjögren’s disease

OBJECTIVES: Early-onset primary Sjögren's disease (pSjD) represents a specific clinical phenotype with poorer prognosis. We aim to compare early- and late-onset pSjD immunophenotypes to identify key distinct immunological features. METHODS: We retrospectively studied 204 newly diagnosed, untreated pSjD patients categorized by age at diagnosis (≤35 years). Clinical features, peripheral lymphocyte profiles, CD4+ T cell subsets and cytokine levels were compared. Key immune variables were screened via random forest and LASSO regression. LASSO-selected variables were analysed using forward stepwise logistic regression to determine independent immune factors associated with early-onset pSjD. RESULTS: Among 204 enrolled patients, 43 (21.08%) were classified as early-onset pSjD and 161 (78.92%) as late-onset pSjD. Compared with the late-onset group, early-onset patients showed significantly lower CD4+ T cell counts [442.62 (236.92-558.89) vs 563.11 (386.98-762.60), P = 0.005] and NK cell counts [71.36 (51.69-134.58) vs 138.05 (91.65-241.90), P < 0.001]. In terms of CD4+ T cell subsets, the early-onset group exhibited higher Th17/Treg cell ratios [0.42 (0.33-0.59) vs 0.30 (0.21-0.46), P = 0.006] and lower Treg cell counts [22.07 (12.89-34.96) vs 28.00 (20.35-38.93), P = 0.032]. Three independent factors for early-onset disease were identified: NK cell counts (OR = 0.993, P = 0.010), CD4+ T cell percentage (OR = 0.947, P = 0.019) and Th17/Treg cell ratios (OR = 5.215, P = 0.029). CONCLUSION: This study characterizes the distinct peripheral immunological landscapes of early- and late-onset pSjD and identifies an immunological triad that may represent a unique 'immune endotype' for early-onset disease, offering insights into targeted monitoring and therapies.