Impact of smoking status on Sjögren's disease diagnosis and phenotype: results from a cohort study with matched population controls

To examine associations between smoking and Sjögren's disease (SjD) diagnosis, compared with non-Sjögren's sicca syndrome (sicca) and population controls, and to explore immunomodulatory effects of smoking on disease phenotype.

Adults referred for suspected SjD to the Optimising Assessment in Sjögren's Syndrome (OASIS) cohort from 2014 until 2023 were classified as SjD or sicca. Smoking status, exposure (pack-years) and passive smoking history were recorded through standardized questionnaires. Associations with diagnosis, clinical and serological parameters, and patient-reported outcomes were analysed using multivariate logistic and linear regression. Smoking patterns were further compared with matched controls from the 2018 UK Annual Population Survey.

A total of 317 SjD patients and 170 sicca controls were included. Of these, 257 SjD met 2016 classification criteria, and were used for primary analyses. Smoking data were available for 85.0% of the cohort. SjD patients were more frequently never smokers than sicca (70.5% vs 53.1%, P = 0.002). In the multivariate analysis, current smoking (odds ratio 0.37, 95% CI 0.15-0.92) was independently associated with lower odds of SjD. Never smokers exhibited higher IgG levels (P = 0.003) and more frequent biological EULAR Sjögren's Disease Activity Index activity (P = 0.038). Smoking exposure correlated with reduced IgG, RF levels and seropositivity, independent of DMARD use. Compared with population controls, sicca, but not SjD, showed higher ever-smoking rates (49.6% vs 39.1%, P = 0.049).

Smoking was negatively associated with SjD diagnosis compared with sicca, but not population controls. Smoking exposure was linked to lower immunoglobulin and autoantibody levels, suggesting an immunomodulatory effect rather than true disease protection. Findings support a potential metabolically influenced, non-autoimmune, sicca phenotype linked to smoking.