Inhibitory activity of FOXP3+ regulatory T cells reveals high specificity for displaying immune tolerance in remission state rheumatoid arthritis

Sci Rep. 2020 Nov 13;10(1):19789. doi: 10.1038/s41598-020-76168-1.

Abstract

Immune regulation status may indicate immunological remission in rheumatoid arthritis (RA). This cross-sectional study aimed to determine the Regulatory T cell (Treg) properties, together with 14 plasma cytokines levels between active RA and clinical remission patients. Peripheral blood (PB) Foxp3+ Treg was collected from RA patients for determination of Treg inhibitory activity using a co-culture system. Other PB T cell types and plasma cytokines were determined by flow-cytometry. The Treg results were analyzed according to the disease activity score-28 (DAS28). Then sensitivity and specificity were calculated for the indication of the remission status. The number and inhibitory activity of Treg are higher in the clinical remission as compared to the active RA (p value < 0.0001). Also, Treg: CD4+CD25+CD127+ cell ratio demonstrates the similar result (p value < 0.05). Treg inhibitory activity is inversely correlated with the DAS28. Specificity and positive likelihood ratio of inhibitory activity for indicating remission status are 92.31% (95% CI 63.97-99.81) and 11.14 (95% CI 1.67-74.14), respectively. Treg inhibitory activity is a promising prognostic marker and probably represents the immunological remission status in RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism*
  • Biomarkers / blood
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Humans
  • Interleukin-10 / blood
  • Interleukin-2 / blood
  • Interleukin-2 Receptor alpha Subunit / blood
  • Interleukin-22
  • Interleukin-4 / blood
  • Interleukin-5 / blood
  • Interleukin-6 / blood
  • Interleukin-7 Receptor alpha Subunit / blood
  • Interleukin-9 / blood
  • Interleukins / blood
  • Male
  • Prognosis
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*

Substances

  • Biomarkers
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-5
  • Interleukin-6
  • Interleukin-7 Receptor alpha Subunit
  • Interleukin-9
  • Interleukins
  • Interleukin-10
  • Interleukin-4