Circulating Th17.1 cells as candidate for the prediction of therapeutic response to abatacept in patients with rheumatoid arthritis: An exploratory research

Abstract

T-helper (Th)17.1 cells exhibit high pathogenicity in inflammatory diseases. This study aimed to identify the changes in the proportions of Th subsets, including Th17.1, which are associated with abatacept treatment response in Japanese patients with rheumatoid arthritis. On the basis of the results, we assessed whether Th17.1 is a potential cellular biomarker. Multicolor flow cytometry was used to determine the circulating Th subsets among CD4+ T lymphocytes in 40 patients with rheumatoid arthritis before abatacept treatment. All the patients received abatacept treatment for 24 weeks; changes in disease activity score, including 28-joint count C-reactive protein, and responsiveness indicated by other indices to abatacept treatment were evaluated according the European League Against Rheumatism criteria (good and moderate responders and nonresponders). The correlation between the abatacept responses and the proportions of Th subsets (baseline) was analyzed. Logistic regression analysis with inverse probability weighting method was performed to calculate the odds ratio adjusted for patient characteristics. The proportion of baseline Th17.1 cells was significantly lower in patients categorized as good responders than in those categorized as non-good responders (moderate responders and nonresponders; p = 0.0064). The decrease in 28-joint count C-reactive protein after 24 weeks of abatacept therapy showed a significant negative correlation with the proportion of Th17.1 cells. The adjusted odds ratio for achieving good response in patients with baseline Th17.1 levels below the median value was 14.6 (95% confidence interval, 2.9–72.3; p = 0.0021) relative to that in the remaining patients. The proportion of Th17.1 cells at baseline is a good candidate for predicting abatacept treatment response in Japanese patients. These novel findings may represent a significant step in the pursuit of precision medicine.

Imbalanced Immune Response of T-Cell and B-Cell Subsets in Patients with Moderate and Severe COVID-19

“…We found that Th17.1-like cells were significantly increased within the total Th17-like subset in severe COVID-19 compared to those in moderate COVID-19 and in the HD. It has been shown that Th17.1 cells produce cytokines, including IL-17A, GM-CSF, IFN-γ, and TNF-α, which are associated with inflammatory conditions [ 59 , 60 ] and influence different cell types at the site of infection, including tissue macrophages, epithelial cells, and endothelial cells by inducing pro-inflammatory mediator expression and promoting neutrophil recruitment [ 61 ]. Thus, Th17.1 and their cytokines could be involved in secondary tissue damage during severe SARS-CoV-2 infection, but the role of Th17 cells in COVID-19 pathogenesis remains unknown.…”

Peripheral blood CD4posCD25posFoxP3pos cells and inflammatory cytokines as biomarkers of response in rheumatoid arthritis patients treated with CTLA4-Ig

“…Along this line, CTLA4-Ig treatment was found to significantly reduce T-cell repertoire restriction [ 24 ] and to significantly increase peripheral blood-derived CD4 pos CD25 pos FoxP3 pos regulatory T lymphocyte rate in RA patients together with their apoptosis [ 25 ]. However, conflicting data were produced about the relation between peripheral blood-derived activated Th17 cells and CTLA4-Ig induced disease remission in RA patients [ 26 , 27 ], while peripheral blood-derived activated Treg cells before treatment were found to be significantly higher in RA patients achieving disease remission with CTLA4-Ig [ 26 ]. In our study, we found that CTLA4-Ig treatment significantly reduces the rates of peripheral blood-derived CD4 pos CD25 pos FoxP3 pos cells in RA patients regardless of their disease duration.…”

YY1 regulation by miR-124-3p promotes Th17 cell pathogenicity through interaction with T-bet in rheumatoid arthritis

“…Pathogenic Th17 cells are considered to be involved in RA pathogenesis. Targeting pTh17 cells or associated molecules may be a potential strategy for clinical diagnosis, treatment, and prognosis of RA ( 24 , 25 ). In our previous study, we observed that transcription factor YY1 was overexpressed in RA patients and promoted Th17 cell polarization by regulating IL-6 ( 16 ).…”