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Increased serum soluble interleukin-2 receptor levels in dermatomyositis are associated with Th17/Treg immune imbalance

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Abstract

Dermatomyositis (DM) represents a multifaceted chronic inflammatory myopathy, primarily manifesting as progressive deterioration of muscular and cutaneous tissues. Despite an incomplete comprehension of DM's etiology and pathogenesis, current evidence implicates the involvement of T lymphocyte infiltration, extensive cytokine release, myositis-specific antibodies, and myositis-associated antibodies in disease development. Serum soluble interleukin-2 receptor (sIL-2R) frequently serves as a marker for T cell activation; however, its role remains elusive. Consequently, this investigation sought to elucidate the association between sIL-2R levels, peripheral blood lymphocyte subset counts, and related cytokines in DM patients, with the aim of uncovering the intricate mechanisms underlying DM and establishing a theoretical foundation for the implementation of precise, targeted, individualized immunomodulatory therapy. In this study, a cohort of 60 dermatomyositis (DM) patients, comprising 32 with inactive DM and 28 with active DM, was enrolled and stratified into inactive and active groups based on the Myositis Disease Activity Visual Analogue Scale (MYOACT). Flow cytometry was employed to quantify the absolute counts of peripheral lymphocyte subsets and CD4+T cell subsets in each group, while a flow cytometry bead array was utilized to measure serum cytokine levels. In a comparative analysis between healthy individuals and patients diagnosed with DM, we observed a marked elevation in serum sIL-2R concentrations (P < 0.001) and T-helper 17 cell/regulatory T cell (Th17/Treg) ratios (P < 0.01) within the latter group. A positive correlation was identified between serum sIL-2R levels and various parameters, including ESR, CRP, VAS, AST, CKMB, LDH, HBDH, PT, APTT, DDi, IL-6, IL-10, and IFN-γlevels (P < 0.05). In contrast, serum sIL-2R levels demonstrated a negative correlation with LY, HGB, ALB, Th17 cell populations, and Th17/Treg cell ratios (P < 0.05). Employing multivariate logistic regression, we identified serum sIL-2R concentrations as an independent risk factor for both disease activity and hepatic involvement in DM patients. Moreover, receiver operating characteristic (ROC) curve analyses revealed that serum sIL-2R levels significantly contributed to the differentiation of disease activity and the detection of liver involvement in DM patients, with areas under the ROC curve (AUC) of 0.757 (95% CI 0.630–0.884, P = 0.001) and 0.826 (95% CI 0.717–0.935, P < 0.001), respectively. This study highlights the potential utility of serum sIL-2R levels as a valuable biomarker for assessing disease activity and liver involvement in dermatomyositis. Elevated serum concentrations of sIL-2R were observed in patients with DM, exhibiting significant associations with Th17 cell populations and Th17/ Treg ratios. These findings indicate that sIL-2R may be implicated in the immunopathogenesis of DM, thereby warranting further investigation to elucidate its role in the disease process.

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Availability of data and materials

The datasets during this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81971543); Key Research and Development (R&D) Projects of Shanxi Province (201803D31119) and Four “Batches” Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province (No. 2022XM05).

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Authors and Affiliations

  1. Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China

    Yuhuan **e, Tingting Zhang, Rui Su, Lu Liu, Lei Jiang, Hongwei Xue, **aofeng Li & Caihong Wang

  2. Shanxi Key Laboratory of Immunomicroecology, Taiyuan, Shanxi, China

    Yuhuan **e, Tingting Zhang, Rui Su, Lu Liu, Lei Jiang, Hongwei Xue, **aofeng Li & Caihong Wang

  3. Pathology, Joint Program in Transfusion Medicine, Brigham and Women’s Hospital/Children’s Hospital, Harvard Medical School, Boston, MA, USA

    Chong Gao

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  1. Yuhuan **e
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  9. Caihong Wang
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Contributions

YX performed data analysis, drew illustrations, and drafted the manuscript. RS, TZ and HX participated in the collection and organization of clinical data. LL and LJ participated in data analysis. CG and XL participated in study design and manuscript revision. CW conceived the topic of the manuscript, critically revised the content of the manuscript, and made substantial contributions throughout the study. All approved the publication of the manuscript.

Corresponding author

Correspondence to Caihong Wang.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical approval

This study was approved by the Ethics Committee of the Second Hospital of Shanxi Medical University (Approval (2019) KY No. (105)).

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**e, Y., Zhang, T., Su, R. et al. Increased serum soluble interleukin-2 receptor levels in dermatomyositis are associated with Th17/Treg immune imbalance. Clin Exp Med 23, 3605–3617 (2023). https://doi.org/10.1007/s10238-023-01155-5

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