Rheumatology International

, Volume 38, Issue 8, pp 1511–1519 | Cite as

Higher levels of serum interleukin-35 are associated with the severity of pulmonary fibrosis and Th2 responses in patients with systemic sclerosis

  • Jie Tang
  • Ling LeiEmail author
  • Jie Pan
  • Cheng Zhao
  • Jing Wen
Observational Research


The aim of the study is to investigate the levels of serum interleukin-35 (IL-35) before and after treatment and its relationship with clinical parameters as well as the frequency of different subsets of CD4+ T cells in patients with systemic sclerosis (SSc) to explore the role of IL-35 in the pathogenesis of SSc. The levels of serum IL-35, interferon-γ (IFN-γ), IL-4, IL-17A, and IL-10 in 49 patients with SSc and 50 age- and gender-matched healthy subjects were measured by enzyme-linked immunosorbent assay (ELISA). The percentages of peripheral blood Th1, Th2, Th17 cells and Tregs in 49 SSc patients and 20 healthy controls were characterized by flow cytometry. The relationship between the levels of serum IL-35 and the percentages of different subsets of CD4+ T cells, disease duration, the values of forced vital capacity (FVC), modified Rodnan skin scores (MRSS) or high-resolution computed tomography (HRCT) scores was analyzed in patients with SSc. The levels of serum IL-35 in SSc patients were significantly higher than that of healthy controls (P < 0.001), but significantly reduced after treatment for 3 months (P = 0.001). The levels of serum IL-35 were positively correlated with the HRCT scores in SSc patients (P = 0.014) and with disease duration in patients with diffuse cutaneous SSc (P = 0.03), but negatively correlated with the FVC values in SSc patients (P = 0.034). In comparison with that in the healthy controls, significantly decreased percentages of Th1, but increased Th2 and Th17 cells were detected in patients, leading to reduced ratios of Th1/Th2 and increased ratios of Th17/Tregs (P < 0.001). The levels of serum IL-35 were positively correlated with IL-4 (P = 0.036) and tended to be positively associated with the frequency of Tregs in SSc patients (P = 0.054). Higher levels of serum IL-35 may be associated with the development of SSc and severity of pulmonary fibrosis in SSc patients.


Interleukin-35 Different subsets of CD4+ T cells Interleukin-4 Systemic sclerosis 



The authors would like to express their appreciation to Professor Jia-Quan Li, Guangxi Medical University, for his assistance and advice in performing experiments. This manuscript has been edited and proofread by Medjaden Bioscience Limited.

Author contributions

Jie Tang carried out the experiments, data collection and interpretation and writing the manuscript. Ling Lei designed the study, analyzed and interpreted the data, reviewed the manuscript, and supervised the entire study. Jie Pan helped to perform experiments and data acquisition. Cheng Zhao and Jing Wen participated in data collection and analysis. All authors read and approved the final manuscript.


This study was supported by grants from the Guangxi Natural Science Foundation (Grant No. 2016GXNSFAA380175).

Compliance with ethical standards

Ethical approval

This study was approved by the Ethical Committee of the First Affiliated Hospital of GuangXi Medical University. Written informed consent was obtained from all patients and healthy controls.

Conflict of interest

All authors have no conflict of interest to declare. There is no any interest or relationship with pharmaceutical agencies within the past 36 months.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Rheumatology and Clinical ImmunologyThe First Affiliated Hospital of Guangxi Medical UniversityNanningChina

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