Transcriptomic profiling and longitudinal study reveal the relationship of anti-MDA5 titer and type I IFN signature in MDA5+ dermatomyositis

Yan Wang; Hongxia Jia; Wei Li; Hongping Liu; Meng Tu; Jing Li; Jiuling Cheng; Guojun Zhang

doi:10.3389/fimmu.2023.1249844

Transcriptomic profiling and longitudinal study reveal the relationship of anti-MDA5 titer and type I IFN signature in MDA5+ dermatomyositis

Front Immunol. 2023 Aug 28:14:1249844. doi: 10.3389/fimmu.2023.1249844. eCollection 2023.

Authors

Yan Wang¹, Hongxia Jia¹, Wei Li², Hongping Liu¹, Meng Tu¹, Jing Li¹, Jiuling Cheng¹, Guojun Zhang¹

Affiliations

¹ Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Department of Rheumatology and Immunology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Objective: This study aimed to investigate the relationship between anti-MDA5 titer and type I IFN signature in patients with MDA5+ DM.

Methods: We explored the transcriptome profiling of PBMCs in MDA5+ DM patients with high-titer of antibody at disease onset or relapse and normal low-titer after treatment and healthy donors. Subsequently, we revealed the dynamic relationship between serum type I IFN scores and antibody titers.

Result: Differentially expressed genes in MDA5+ DM patients were enriched for related pathways and biological functions linked to viruses and cytokines compared to healthy donors. Similar differences remained pooled between the high-titer and low-titer group, and type I-specific interferon response genes showed upregulation in high-titer group. Significant correlations were found between anti-MDA5 titers and type I IFN scores (r = 0.50, P< 0.001). Contemporaneous anti-MDA5 titers revealed to be significantly higher in the group with ultra-high type I IFN scores (vs. high group, P = 0.027; vs. low group, P< 0.001). Longitudinal assessment of type I IFN scores and anti-MDA5 titers, including pre- and post-treatment changes at initial diagnosis and dynamic changes during treatment, presented an asynchrony between the two parameters in response to treatment.

Conclusion: Anti-MDA5 antibody titers correlated with type I IFN signature in patients with MDA5+ DM and they both changed dynamically but not synchronously over the course of treatment.

Keywords: autoantibody; dermatomyositis; interstitial lung disease; melanoma differentiation-associated gene 5; type I interferon.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies
Dermatomyositis* / genetics
Gene Expression Profiling
Humans
Interferon Type I*
Longitudinal Studies
Transcriptome

Substances

Antibodies
Interferon Type I

Grants and funding

This work was funded by the Key Laboratory of Interstitial Lung Disease in Henan Province and Lung Transplantation and Clinical Research Center for Respiratory Disease in Henan Province.