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

• Published in: Frontiers in immunology 2023-08, Vol.14, p.1249844
• Main Authors: Wang, Yan, Jia, Hongxia, Li, Wei, Liu, Hongping, Tu, Meng, Li, Jing, Cheng, Jiuling, Zhang, Guojun
• Format: Article
• Language: English
• Subjects: autoantibody; dermatomyositis; Immunology; interstitial lung disease; melanoma differentiation-associated gene 5; type I interferon
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1249844

This study aimed to investigate the relationship between anti-MDA5 titer and type I IFN signature in patients with MDA5+ DM.ObjectiveThis study aimed to investigate the relationship between anti-MDA5 titer and type I IFN signature in patients with MDA5+ DM.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.MethodsWe 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.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.ResultDifferentially 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 async