Aberrant IL-35 levels in patients with primary Sjogren's syndrome

Scand J Immunol. 2018 Nov;88(5):e12718. doi: 10.1111/sji.12718.

Abstract

Objective: IL-35 is a newly discovered immunoregulatory cytokine that possesses the ability to inhibit CD4 + effector T cells and alleviate autoimmune diseases. The objective of this study was to investigate IL-35 levels in patients with primary Sjogren's syndrome (pSS) and explore the roles of IL-35 in the pathogenesis of pSS.

Methods: Thirty-four hospitalized patients with pSS were recruited, and 34 volunteers were enrolled as healthy controls. An ELISA was adopted to measure plasma IL-35 levels. The levels of P35 and EBI3 mRNAs in peripheral blood mononuclear cells (PBMCs) were determined using real-time quantitative PCR. The percentage of CD4 + EBI3 + T cells and CD19 + EBI3 + B cells was analysed using flow cytometry. Correlations between IL-35 levels, P35 and EBI3 mRNAs, numbers of CD4 + EBI3 + T cells, CD19 + EBI3 + B cells and clinical parameters were analysed.

Results: Significantly lower plasma IL-35 levels, P35 and EBI3 mRNA levels, and percentages of CD4 + EBI3 + T cells but increased percentages of CD19 + EBI3 + B cells were observed in patients with pSS than in healthy controls. IL-35 levels, EBI3 mRNA expression and the percentage of CD4 + EBI3 + T cells exhibited negative correlations with the ESSDAI score, whereas levels of the IL-35 protein and EBI3 mRNA were negatively correlated with the ESR. Patients who were positive for anti-SSB antibodies presented with lower IL-35 levels and percentages of CD4 + EBI3 + T cells.

Conclusions: Based on these results, a decrease in the IL-35 levels may play an important role in the pathogenesis of pSS. IL-35 may act as a potential therapeutic agent against inflammation in patients with pSS.

Keywords: CD19 + EBI3 + B cells; CD4 + EBI3 + T cells; IL‐35; Sjogren's syndrome.

MeSH terms

  • Adult
  • Autoantibodies / blood*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Blood Sedimentation
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • Case-Control Studies
  • Female
  • Gene Expression Regulation
  • Humans
  • Interleukin-12 Subunit p35 / genetics
  • Interleukin-12 Subunit p35 / immunology*
  • Interleukins / genetics
  • Interleukins / immunology*
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / immunology*
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology
  • Severity of Illness Index
  • Sjogren's Syndrome / diagnosis
  • Sjogren's Syndrome / genetics
  • Sjogren's Syndrome / immunology*
  • Sjogren's Syndrome / pathology
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / pathology

Substances

  • Autoantibodies
  • EBI3 protein, human
  • Interleukin-12 Subunit p35
  • Interleukins
  • Minor Histocompatibility Antigens
  • RNA, Messenger
  • interleukin-35, human