Abstract
BackgroundIt is not known if sex-based disparities in immunological factors contribute to the disease process in rheumatoid arthritis (RA). Hence, we examined whether circulating T cell subset proportions and their association with disease activity differed in male and female patients with untreated early rheumatoid arthritis (ueRA).MethodsProportions of T cell subsets were analyzed in peripheral blood from 72 ueRA DMARD- and corticosteroid-naïve patients (50 females and 22 males) and in 31 healthy age- and sex-matched controls. Broad analysis of helper and regulatory CD4+ T cell subsets was done using flow cytometry. Disease activity in patients was assessed using DAS28, CDAI, swollen joint counts, tender joint counts, CRP, and ESR.ResultsMultivariate factor analyses showed that male and female ueRA patients display distinct profiles of association between disease activity and circulating T cell subset proportions. In male, but not female, ueRA patients Th2 cells showed a positive association with disease activity and correlated significantly with DAS28-ESR, CDAI, and swollen and tender joint counts. Likewise, proportions of non-regulatory CTLA-4+ T cells associated positively with disease activity in male patients only, and correlated with DAS28-ESR. In contrast, there was a negative relation between Th1Th17 subset proportions and disease activity in males only. The proportions of Th17 cells correlated positively with DAS28-ESR in males only, while proportions of Th1 cells showed no relation to disease activity in either sex. There were no significant differences in proportions of T cell subsets between the sexes in patients with ueRA.ConclusionsOur findings show sex-based differences in the association between T cell subsets and disease activity in ueRA patients, and that Th2 helper T cells may have a role in regulating disease activity in male patients.
Highlights
It is not known if sex-based disparities in immunological factors contribute to the disease process in rheumatoid arthritis (RA)
Male and female untreated early RA patients show different profiles of association between T cell subsets and disease activity Based on the gating strategy presented in Fig. 1a-c we first examined the proportions of T helper (Th) and regulatory CD4+ T cell subsets in male and female untreated early rheumatoid arthritis (ueRA) patients
By the use of cluster analysis, i.e. Principal component analysis (PCA), we investigated whether patient sex affects the relationship between proportions of T cell subsets and common disease activity measures used when assessing RA patients (Fig. 2a-b)
Summary
It is not known if sex-based disparities in immunological factors contribute to the disease process in rheumatoid arthritis (RA). We examined whether circulating T cell subset proportions and their association with disease activity differed in male and female patients with untreated early rheumatoid arthritis (ueRA). Male RA patients have shown a higher remission rate than female patients in response to biologic and non-biologic disease-modifying anti-rheumatic drug (DMARD) treatments [7, 8]. Another study showed that males were only more likely to achieve sustained remission in early RA, not in established RA, when treated with both biologic and non-biologic DMARD [10]. These results indicate that the initial immunological mechanisms responsible for RA may differ in males and females
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