Increased Serum Interleukin-2 Levels Are Associated with Abnormal Peripheral Blood Natural Killer Cell Levels in Patients with Active Rheumatoid Arthritis

Mediators Inflamm. 2020 Sep 15:2020:6108342. doi: 10.1155/2020/6108342. eCollection 2020.

Abstract

Objective: To investigate the relationship between serum interleukin-2 (IL-2) levels and disease activity, absolute numbers of peripheral lymphocyte subsets, autoantibodies, and associated cytokines in patients with rheumatoid arthritis (RA).

Methods: This study included 106 patients with RA, evaluated their disease activity (DAS28 score), and divided them into disease remission (DAS28 ≤ 2.6), low disease activity (DAS28 ≤ 3.2), and moderate-high disease activity (DAS28 > 3.2) groups. Flow cytometry was used to detect the absolute numbers of peripheral lymphocyte subpopulations and CD4+ T cell subsets in each group, and serum cytokine levels were measured using cytometric bead array.

Results: Serum IL-2 levels in RA patients were positively correlated with disease activity and rheumatoid factor titers (p < 0.001 and p = 0.045, respectively), and multiple regression analysis revealed that serum IL-2 levels were an independent factor affecting disease activity. Serum IL-2 levels were positively correlated with Th17/Treg ratios (p = 0.013). Compared with the remission group, peripheral lymphocyte and CD4+ T lymphocyte subsets in patients with active RA decreased to varying degrees; however, the numbers of peripheral natural killer (NK) cells were significantly higher in the moderate-high disease activity group than in the remission (p = 0.046) and low disease activity (p = 0.020) groups; the percentages of NK cells had the same trend. In addition, the number and percentage of NK cells were positively correlated with serum IL-2 levels (p = 0.018 and p = 0.006, respectively).

Conclusions: In RA patients, serum IL-2 levels were not only correlated with patients' disease activity and autoantibody levels but were also involved in their Th17/Treg immune imbalance. In addition, in patients with active RA, NK cell levels were abnormally elevated, possibly due to high serum levels of IL-2.

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / blood*
  • Autoantibodies / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Chi-Square Distribution
  • Female
  • Flow Cytometry
  • Humans
  • Interleukin-2 / blood*
  • Killer Cells, Natural / metabolism*
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells / metabolism

Substances

  • Autoantibodies
  • Interleukin-2