Background Increased exposure to sodium chloride has been associated with an increased activation of Th17 cells and with increased risk of experimental encephalitis in mice as well as an increased T cell activation in humans [1,2]. Provided the postulated role of Th17 cells in rheumatoid arthritis (RA) , it is of interest to investigate the effects of sodium intake on risk for different variants of RA and other known risk factors such as smoking.
Objectives To investigate the relationship between consumption of sodium chloride, smoking and seropositivity among individuals with RA.
Methods Incident cases with early RA (n=1049) participating in the Epidemiological Investigation of Rheumatoid Arthritis (EIRA)  cohort study were analysed. Presence of anti-citrullinated peptides antibodies (ACPA) and rheumatoid factor (RF) was assessed by standard laboratory procedures. Previous and present smoking was reported by the participants of the study in self-reporting questionnaires. Sodium intake was assessed on basis of food frequency questions and analysed as tertiles adjusted by total energy intake. The lowest tertile of sodium intake was used as reference and compared to the combined upper two tertiles. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs) by means of logistic regression analysis with adjustment for age and sex.
Results High consumption of sodium in current smokers was associated with an increased risk for ACPA positivity compared with smokers with low sodium intake (OR=2.21, 95% CI 1.26-3.89). There was a significant interaction between smoking and sodium intake using both additative and multiplicative methods for calculation (AP=0.55, 95% CI 0.25-0.85, RERI=1.41, 95% CI 0.28-2.55, MI p=0.046). There were no significant associations of RF positivity and sodium intake among smokers (OR=1.35, 95% CI 0.81-2.27). Nor were there any significant associations between ACPA or RF positivity and sodium intake among non-smokers (OR=0.96, 95% CI 0.64-1.46 for ACPA, and OR=0.98, 95% CI 0.58-1.66 for RF).
Conclusions High dietary intake of sodium among smokers was associated with an increased risk to develop ACPA positive RA and there was a significant interaction between the two environmental factors – sodium intake and smoking in conferring to this increased disease risk. The present study thus extends a previous study from three of us (BS, IJ and SRD) on impact of sodium on risk for RA in a pre-RA cohort (5). The possibility that smoking may be involved in triggering of Th17 activation of pathogenic importance in ACPA positive RA, and that such events may be modified by dietary intake of sodium chloride now requires experimental studies for eventual molecular verification. If verified, these observations may provide leads for preventive as well as therapeutic efforts by means of dietary changes and/or targeting of sodium-chloride-dependent molecular pathways.
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Disclosure of Interest None declared
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