Roles of biomarkers in anti-MDA5-positive dermatomyositis, associated interstitial lung disease, and rapidly progressive interstitial lung disease

Abstract

Background: Anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (MDA5⁺ DM) is significantly associated with interstitial lung disease (ILD), especially rapidly progressive ILD (RPILD) due to poor prognosis, resulting in high mortality rates. However, the pathogenic mechanism of MDA5⁺ DM-RPILD is unclear. Although some MDA5⁺ DM patients have a chronic course of ILD, many do not develop RPILD. Therefore, the related biomarkers for the early diagnosis, disease activity monitoring, and prediction of the outcome of RPILD in MDA5⁺ DM patients should be identified. Blood-based biomarkers are minimally invasive and can be easily detected.

Methods: Recent relative studies related to blood biomarkers in PubMed were reviewed.

Results: An increasing number of studies have demonstrated that dysregulated expression of blood biomarkers related to ILD such as ferritin, Krebs von den Lungen-6 (KL-6), surfactant protein-D (SP-D), and cytokines, and some tumor markers in MDA5⁺ DM may provide information in disease presence, activity, treatment response, and prognosis. These studies have highlighted the great potentials of blood biomarker values for MDA5⁺ DM-ILD and MDA5⁺ DM-RPILD. This review provides an overview of recent studies related to blood biomarkers, besides highlighted protein biomarkers, including antibody (anti-MDA5 IgG subclasses and anti-Ro52 antibody), genetic (exosomal microRNAs and neutrophil extracellular traps related to cell-free DNA), and immune cellular biomarkers in MDA5⁺ DM, MDA5⁺ DM-ILD, and MDA5⁺ DM-RPILD patients, hopefully elucidating the pathogenesis of MDA5⁺ DM-ILD and providing information on the early diagnosis, disease activity monitoring, and prediction of the outcome of the ILD, especially RPILD.

Conclusions: Therefore, this review may provide insight to guide treatment decisions for MDA5⁺ DM-RPILD patients and improve outcomes.

Keywords: MDA5; biomarker; dermatomyositis; interstitial lung disease; rapidly progressive interstitial lung disease.

FIGURE 1

Proposed possible pathogenesis of MDA5⁺DM‐ILD and summary of blood‐based biomarkers for MDA5⁺DM, MDA5⁺DM‐ILD, and MDA5⁺DM‐RPILD. The potential pathogenesis of MDA5⁺DM‐ILD is presented both on the left (mainly) and right. Blood biomarkers related to MDA5⁺DM, MDA5⁺DM‐ILD, and MDA5⁺DM‐RPILD are on the right. Bold red and blue texts represent upregulated and downregulated biomarkers, respectively. CCL22, C‐C motif ligand 22; cfDNA, cell‐free DNA; CYFRA21‐1, cytokeratin‐19 fragment; DM, dermatomyositis; HNE‐DNA, human neutrophil elastase‐DNA; IFN, interferon; IL‐15, interleukin 15; ILD, interstitial lung disease; KL‐6, krebs von den Lungen‐6; MDA5, melanoma differentiation‐associated gene 5; miR, microRNA; MPO‐DNA, myeloperoxidase‐DNA; NETs, neutrophil extracellular traps; sCD206, soluble CD206; TFH, T follicular helper; YKL‐40, chitinase‐3‐like‐1 protein.