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Analysis of PD-1 and Tim-3 expression on CD4+ T cells of patients with rheumatoid arthritis: Negative association with DAS28

Clinical Rheumatology Apr 12, 2018

Koohini Z, et al. - Researchers assessed the expression of T cell immunoglobulin and mucin-domain containing-3 (Tim-3) and programmed cell death-1 (PD-1) on CD4+ T cells of patients with rheumatoid arthritis (RA). They also evaluated the association of Tim-3 and PD-1 expression with disease activity of RA patients. Findings suggested an involvement of Tim-3 and PD-1 in the immune dysregulation mechanisms of rheumatoid arthritis and for determination of disease activity and progression, these could be considered as useful biomarkers.

Methods

  • In this study, authors included a total of 37 RA patients and 31 sex- and age-matched healthy controls.
  • They determined the disease activity of RA patients by Disease Activity Score of 28 joints scoring system (DAS28).
  • In order to determine the frequency of Tim-3+/PD-1+/CD4+ T cells, a three-color flow cytometry method was applied.
  • The peripheral blood mononuclear cells (PBMCs) were stimulated with PMA/ionomycin to measure the cytokine production.
  • Experts measured the concentrations of IL-17, IL-10, IFN-γ, and TNF-α in culture supernatants by ELISA.

Results

  • Findings suggested the frequency of PD-1+/CD4+ and Tim-3+/PD-1+/CD4+ T cells was significantly higher in patients with RA vs that in controls (p=0.0013 and p=0.050, respectively).
  • As per data, a similar percentage of Tim-3+/CD4+ T cells was seen in patients and controls (p=0.4498).
  • They found that the RA patients have produced significant higher levels of TNF-α, IL-17, and IFN-γ than those of healthy controls (p=0.0121, p=0.0417, and p=0.0478, respectively).
  • Results demonstrated an inverse association between the frequency of Tim-3+/CD4+ cells and DAS28 of RA patients (r = - 0.4696, p=0.0493).
  • Researchers noted that the percentage of Tim-3+/PD-1+/CD4+T cells was also revealed an inverse correlation with DAS28 (r = - 0.5268, p=0.0493).
  • Also, they detected significant positive correlations between the concentrations of TNF-α (r = 0.6418, p=0.0023) and IL-17 (r = 0.4683, p=0.0373) with disease activity of RA patients.

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