Integrating basal and reserve salivary function defines clinically anchored functional phenotypes and contextualises salivary end points in Sjögren's disease.

BACKGROUND

Salivary gland dysfunction in Sjögren's disease (SjD) is clinically heterogeneous. Unstimulated whole salivary flow (UWSF) reflects basal secretion, while stimulated tests such as the Saxon test assess secretory reserve. Whether integrating these complementary domains defines clinically meaningful glandular functional states remains unclear.

METHODS

We conducted a retrospective cohort study of 193 anti-Sjögren's syndrome antigen A (anti-SSA)-positive patients with SjD. Using established clinical thresholds for UWSF and the Saxon test, we defined three functional phenotypes: preserved basal and reserve (PP), partial impairment (PL/LP) and combined low function (LL). Clinical features, patient-reported outcomes, submandibular gland (SMG) gland ratio and longitudinal salivary changes were evaluated.

RESULTS

Dryness and swallowing difficulty differed significantly across phenotypes. Compared with PP, the LL phenotype exhibited higher European Alliance of Associations for Rheumatology (EULAR) Sjögren's Syndrome Patient-Reported Index dryness (β=1.67, 95% CI 0.64 to 2.70) and increased odds of swallowing difficulty (OR 6.19, 95% CI 2.71 to 14.9) after multivariable adjustment. Histological analyses showed markedly reduced SMG preservation in LL. Longitudinally, PP showed measurable declines in UWSF and Saxon test, whereas PL/LP remained relatively stable. LL had minimal longitudinal change in UWSF and a directionally positive Saxon slope, best interpreted in the context of floor-constrained end point behaviour rather than biological recovery. Baseline-to-last transition analyses showed substantial same-phenotype retention, and most longitudinally evaluable LL patients remained below the impaired Saxon threshold throughout follow-up.

CONCLUSION

Integrated basal-reserve functional phenotyping defines clinically and structurally anchored salivary gland functional states in SjD. This framework may support clinical stratification and state-dependent interpretation of longitudinal salivary end points in studies targeting glandular outcomes.