Dysregulated CD38 expression on T cells was associated with rapidly progressive interstitial lung disease in anti-melanoma differentiation-associated gene 5 positive dermatomyositis

Front Immunol. 2024 Nov 11:15:1455944. doi: 10.3389/fimmu.2024.1455944. eCollection 2024.

Abstract

Background: Anti-melanoma differentiation-associated gene 5 positive dermatomyositis (MDA5+ DM) is a life-threatening disease due to rapidly progressive interstitial lung disease (RP-ILD). We aimed to investigate the expression profile of T cell subsets in MDA5+ DM patients, seeking for possible disease-causing T cell subsets and potential biomarkers to distinguish ILD, especially RP-ILD patients.

Methods: Peripheral blood T cell subpopulations were immunophenotyped in 24 MDA5+ DM patients and 21 healthy controls (HCs) by flow cytometry. The proportion of T cell subsets and clinical characteristics were analyzed. The quantitative determination of cytokines in the plasma was measured by using a microsphere-based immunofluorescence assaying kit.

Results: The proportion of naïve and CD38+ T cells were much higher, whereas the proportion of central memory T cells were lower in MDA5+ DM patients than in HCs. Notably, the proportion of CD38+CD4+ T cells and CD38+CD8+ T cells on T cells in in RP-ILD group were significantly elevated compared to C-ILD, non-ILD group and HCs. Moreover, serum IFN-α levels were significantly increased in MDA5+ DM patients with RP-ILD. Further, the frequencies of CD38+CD4+ T cells and CD38+CD8+ T cells were positively correlated with IFN-α levels. Finally, ROC analysis indicated that CD38+CD4+ T cells and CD38+CD8+ T cells could be potential biomarkers for predicting ILD/RP-ILD in MDA5+ DM patients.

Conclusion: Dysregulated CD38 expression on T cell subsets was associated with lung involvement, especially RP-ILD in MDA5+ DM patients. CD38+ T cell subsets could be used as potential biomarkers for predicting ILD/RP-ILD in MDA5+ DM patients.

Keywords: CD38; T cells; anti-MDA5 antibody; dermatomyositis; interstitial lung disease.

MeSH terms

  • ADP-ribosyl Cyclase 1* / metabolism
  • Adult
  • Aged
  • Biomarkers* / blood
  • Dermatomyositis* / blood
  • Dermatomyositis* / immunology
  • Disease Progression
  • Female
  • Humans
  • Immunophenotyping
  • Interferon-Induced Helicase, IFIH1* / immunology
  • Lung Diseases, Interstitial* / blood
  • Lung Diseases, Interstitial* / diagnosis
  • Lung Diseases, Interstitial* / immunology
  • Male
  • Membrane Glycoproteins / blood
  • Middle Aged
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism

Substances

  • Interferon-Induced Helicase, IFIH1
  • IFIH1 protein, human
  • ADP-ribosyl Cyclase 1
  • Biomarkers
  • Membrane Glycoproteins
  • CD38 protein, human

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by Sichuan Science and Technology Program (2024NSFSC1540, 2024YFFK0349) and National Natural Science Foundation of China (No. 82472346, No. 82102466, No. 82272400).