Changes in anti-MDA5 antibody titres and serum cytokine levels before and after diagnosis of anti-MDA5 antibody-positive dermatomyositis

Abstract

Objectives Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) is characterised by rapidly progressive interstitial lung disease and has a poor prognosis. We aimed to investigate whether anti-MDA5 antibody titres and cytokine levels predict clinical course, and evaluate changes in both parameters before and after diagnosis. Methods This was a retrospective, single-centre study in 38 patients with anti-MDA5 antibody-positive DM. We compared clinical characteristics and laboratory data at diagnosis between patients in the treatment response (n = 23) and non-response (n = 15) groups, and between those in the relapse (n = 5) and non-relapse (n = 24) groups. We also measured serum anti-MDA5 antibody titres and cytokine levels before and after diagnosis. Results The non-response group was older, had a higher ground-glass opacity score, lower PaO2/FiO2, higher C-reactive protein (CRP) level, and higher anti-MDA5 antibody titre than the response group. No cytokines significantly differed between groups at diagnosis. The relapse group had a significantly higher anti-MDA5 antibody titre than the non-relapse group. In the survivor group, the anti-MDA5 antibody titre and levels of interferon (IFN)-α, IFN-γ, monocyte chemotactic protein-1 (MCP-1), interleukin (IL)-6, IL-33, CRP, and ferritin were significantly lower 6 months post-treatment than at diagnosis. Macrophage-associated cytokines such as IL-6, IL-8, IL-18, and MCP-1 increased after anti-MDA5 antibody positivity in three patients who were anti-MDA5 antibody-positive before diagnosis. Conclusion The anti-MDA5 antibody titre at diagnosis may predict the clinical course. Levels of macrophage-associated cytokines significantly declined at 6 months post-treatment, and they may have increased after anti-MDA5 antibody titre positivity.

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

“…Our study is consistent with previous evidence that anti-MDA5 titers gradually decrease in response to treatment ( 32 , 37 ), while we also found that IFN levels generally dropped to a state of low activity within a few days after application of steroids and immunosuppressants. The lag in antibody response over IFN signaling in our research may correspond to the increase of cytokine levels after positive anti-MDA5 antibody titers indicated by other studies ( 33 ). To note, both indicators may behave with disparate response at the time of relapse or persistent over-activation as they did at remission, which is a conjecture based on the case of patient S13 in our transcriptomic data, with a concurrent low antibody titer status and high type I IFN signaling.…”

Clinical features of macrophage activation syndrome in adult dermatomyositis: A single‐center retrospective case‐control study

“…In dermatomyositis, autoimmune stimuli incite the activation of alveolar macrophages, prompting the secretion of a spectrum of cytokines, including IL‐6 and IFN‐γ. These mediators, in turn, stimulate neutrophil recruitment and contribute to the induction of pulmonary fibrosis 4,26 . Similarly, the pathogenesis of MAS is intricately linked to the excessive activation and proliferation of macrophages 27 .…”

“…These mediators, in turn, stimulate neutrophil recruitment and contribute to the induction of pulmonary fibrosis. 4 , 26 Similarly, the pathogenesis of MAS is intricately linked to the excessive activation and proliferation of macrophages. 27 Aberrant macrophage activation, coupled with an elevated cytokine release, involves a complex interplay of multiple cell types and cytokines, culminating in an escalating cytokine production and the onset of a cytokine storm.…”

“…The pathogenesis of RP‐ILD patients is still not clear; histopathological examinations of the lung tissues in RP‐ILD patients have revealed the presence of infiltrating alveolar macrophages 3 . Furthermore, the involvement of cytokines associated with macrophage activation, such as interleukin‐6 (IL‐6), interleukin‐18 (IL‐18), and interferon‐gamma (IFN‐γ), may contribute to its pathogenetic mechanisms 4 . Moreover, there is documented evidence establishing a significant association between neopterin, a macrophage activation marker, and RP‐ILD, which suggesting its potential role as a biomarker in the disease evaluation of dermatomyositis 5 …”

“…3 Furthermore, the involvement of cytokines associated with macrophage activation, such as interleukin-6 (IL-6), interleukin-18 (IL-18), and interferon-gamma (IFN-γ), may contribute to its pathogenetic mechanisms. 4 Moreover, there is documented evidence establishing a significant association between neopterin, a macrophage activation marker, and RP-ILD, which suggesting its potential role as a biomarker in the disease evaluation of dermatomyositis. 5 Haemophagocytic syndrome, also called hemophagocytic lymphohistiocytosis (HLH), is a rare immune-mediated life-threatening disease, caused by a dysregulated hyperinflammatory response, associated with aberrant activation of lymphocytes and macrophages, leading to a severe hyperinflammatory condition.…”