Background/Purpose: A comprehensive analysis of the circulating T cell subtype pattern, including T helper 1 (Th1) cells, Th2 cells, Th17 cells, Th1/Th17 cells, T follicular helper (Tfh)  cells, T follicular regulatory (Tfr) cells and T regulatory (Treg) cells in early untreated early RA compared to healthy controls has previously not been published.

Methods: Twenty-six patients with early RA satisfying the ACR 2010 criteria who had not received any DMARDS or prednisolone donated blood together with 18 sex and age matched healthy controls. Peripheral blood mononuclear cells were stained and analyzed by flow cytometry for combinations of chemokine receptors CCR4, CCR6 and CXCR3 to define Th1, Th2, Th17 and Th1/Th17 cells. Follicular T helper cells were defined using the expression of CXCR5 but lack of FOXP3, while follicular regulatory T cells were defined as expressing both CXCR5 and FOXP3. Regulatory T-cells were defined as expressing either CD25 and low CD127 or FOXP3. Analysis of mRNA expression for the respective transcription factors were performed on flow cytometry sorted cells and cytokine production from the cultured sorted T cells was analyzed to confirm that the chemokine receptor expression correctly defined the T cell subtypes. In addition, CTLA-4 was analyzed on both conventional and regulatory CD4+ T-cells. The disease activity of the patients was measured DAS28 and CDAI. The data was analyzed using multivariate factor analyses followed by univariate analyses.

Results: Multivariate discriminant analysis including all T cell subtypes showed that the best discriminators for early RA were the proportions of Th2 and Th17 cells that were found in higher proportions in early RA than in healthy controls and the Th1/Th17 cells that were found in lower fractions in early RA than in controls. Regulatory T cells were found in higher proportions in early RA than in controls, while the proportions of circulating follicular helper T cells did not differ between the groups. Principal component analysis of the T cells subtypes in the patients showed that Th2 cells clustered with the Th17 cells, Th1/Th17 cells clustered with the Th1 cells and Tfh cells clustered with the Tfreg cells, whereas Tregs and Th0 cells were positioned separately. Strong negative correlations were obtained between Th17 cells and the Th1 cells. The clinical inflammatory activity in untreated early RA was unrelated to any of the proportions of the circulating T cells subtypes except for the proportions of the CTLA-4 positive T cells that were positively related to higher clinical activity.

Conclusion: We found a dominance of circulating Th2 cells together with Th17 cells in early RA and the former should attract more attention in relation to pathogenesis of early stages of the disease.  Knowledge on what T cell subtypes dominate in the circulation in early rheumatoid arthritis may also guide us in developing new targeted treatments for this group.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/early-rheumatoid-arthritis-patients-have-higher-fractions-of-circulating-th2-cells-th17-cells-and-regulatory-t-cells-similar-fractions-of-follicular-helper-t-cells-and-lower-fractions-of-th17/