Characterisation of CD4 Th subsets as well as dietary, exercise and lifestyle factors in an established Rheumatoid Arthritis cohort; pilot study.

BackgroundSex disparities in the incidence and severity of Rheumatoid Arthritis (RA) are well-documented, with females experiencing more aggressive disease and different responses to treatment. While underlying mechanisms remain elusive, immune factors and lifestyle components, such as diet and physical activity, could play a role in shaping disease outcomes. Since Th cells are key drivers of RA, this study characterised CD4 Th subset frequencies, including Th1, Th2, Th17 and Th1/17 cells, in a cohort of males and females with established RA. Considering the role of diet and lifestyle in RA development, we also evaluated participant diet and lifestyle patterns. MethodsAn observational cross-sectional cohort study profiling 39 individuals (19 RA and 20 age and sex matched controls) with no major co-morbidities was conducted. Percentages of Th1, Th2, Th17 and Th1/17 cells from peripheral blood were determined by flow cytometry as well as serum levels of RF and cytokines IL17, IFN-{gamma}, TNF-, GM-CSF, TGF-{beta}, IL-6, and CRP by ELISA. Dietary intake was assessed by Food Frequency Questionnaire (FFQ), the Dietary inflammatory Index (DII) calculated from nutrient intake. Physical activity levels were evaluated by Global Physical Activity Questionnaire (GPAQ). ResultsSex-specific differences of Th17, Th1 an Th2 cells were observed in RA groups. Males had lower levels of Th1 cells and higher levels of Th17 cells than control subjects, while females had lower levels of Th2 cells than controls. Female RA subjects had higher ratio of Th1:Th2 cells than controls, while male RA subjects had higher Th17:Th1 ratio than controls. Interestingly, circulating CD4 Th subset levels were predictive of RA in this cohort. No changes in cytokine levels were observed. The male RA group consumed 30% less carbohydrate (RA = 156g +/-57g, Control = 253g +/-59g; p=0.003), 37% less sugar (RA = 74.1g +/-29g, Control = 118g +/-33g; p=0.004) and 30% less dietary fibre (R = 33g +/-8g, Control = 48g +/-13 g; p=0.008) than the male control group. The female RA group had the lowest consumption of alcohol in comparison to female control group (RA = 0.31g, Control = 8.97g; p=0.047). Male subjects had a 4x higher DII than females (p=0.012). ConclusionsOur findings highlight potential sex-specific differences in CD4+ Th cell subsets in individuals with established RA, indicating that sex may influence immune cell composition in this disease. Furthermore, dietary components showed sex-specific consumption patterns, underscoring the potential role of tailored lifestyle interventions in modulating immune responses in RA. Evaluating immunological sex differences and dietary and lifestyle factors may be important for enhancing management strategies in RA.