Transcriptomic Profiling and Longitudinal Study Reveal the Relationship of Anti-MDA5 Titer and Type I IFN Signature in MDA5+ Dermatomyositis

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Sep 13

PMID 37701443

Authors

Yan Wang

Hongxia Jia

Wei Li

Hongping Liu

Meng Tu

Jing Li

Jiuling Cheng

Guojun Zhang

Affiliations

Soon will be listed here.

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, < 0.001). Contemporaneous anti-MDA5 titers revealed to be significantly higher in the group with ultra-high type I IFN scores ( high group, = 0.027; low group, < 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.

Citing Articles

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

Guo Y, Liu H, Chen B, Zhang K, Meng L, Yan L Front Immunol. 2024; 15:1455944.

PMID: 39588376 PMC: 11586385. DOI: 10.3389/fimmu.2024.1455944.

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