Aberrant activation of the type I interferon system may contribute to the pathogenesis of anti‐melanoma differentiation‐associated gene 5 dermatomyositis

Zhang, S.H.; Zhao, Yawen; Xie, Qibing; Jiang, Yanyan; Wu, Yinlan; Yan, Bing

doi:10.1111/bjd.16917

Cited by 62 publications

(51 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Because neopterin is produced in response to IFN‐γ, the high level of neopterin in DM patients may represent an IFN response. In particular, the higher neopterin noted in the anti‐MDA5 antibody‐positive DM may correlate with an elevated IFN response signature that has been reported within this antibody group . Of interest, IFN‐γ has also been noted to play a role in life‐threatening RP‐ILD , but this may also reflect how neopterin may correlate to both RP‐ILD and mortality.…”

Section: Discussionmentioning

confidence: 84%

A high level of serum neopterin is associated with rapidly progressive interstitial lung disease and reduced survival in dermatomyositis

Peng

Zhang

Liang

et al. 2019

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Summary Neopterin is primarily synthesized and released by activated macrophages/monocytes upon stimulation with interferon‐γ and is considered as a marker for macrophage activation. This study aimed to analyze the serum levels of neopterin in patients with dermatomyositis (DM) in association with clinical manifestations, laboratory data and patient prognosis. One hundred and eighty‐two consecutive DM patients and 30 healthy controls were retrospectively enrolled into the study. Serum levels of neopterin were significantly increased in DM patients compared to healthy controls (P < 0·001). High serum neopterin levels were associated with anti‐melanoma differentiation‐associated gene (MDA5) antibody, rapidly progressive interstitial lung disease (RP‐ILD) and characteristic DM cutaneous involvement. Longitudinal assessment of serum samples revealed that the serum neopterin levels were closely correlated with disease severity (β = 30·24, P < 0·001). In addition, a significant increase in serum neopterin concentration of non‐survivors was observed when compared to that of survivors (P < 0·001). Receiver operator characteristic curves showed that serum neopterin could distinguish non‐survivors and survivors at an optimal cut‐off level of 22·1 nmol/l with a sensitivity and specificity of 0·804 and 0·625, respectively (P < 0·001). Kaplan–Meier survival curves revealed that DM patients with serum neopterin > 22·1 nmol/l had a significantly higher mortality compared to the patient group with serum neopterin < 22·1 nmol/l (log‐rank P < 0·001). Multivariate regression analysis identified high serum neopterin concentration to be an independent risk factor for poor prognosis in DM (adjusted hazard ratio = 4·619, 95% confidence interval = 2·092–10·195, P < 0·001). In conclusion, increased serum levels of neopterin were significantly associated with RP‐ILD and reduced survival in DM patients, suggesting it as a promising biomarker in disease evaluation of DM.

show abstract

Section: Discussionmentioning

confidence: 84%

A high level of serum neopterin is associated with rapidly progressive interstitial lung disease and reduced survival in dermatomyositis

Peng

Zhang

Liang

et al. 2019

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…Remarkably, a recent study revealed that these patients showed a high activity of type I IFN system. Although the mechanisms are still unclear, the study detected high levels of transcripts of IFN-associated sensors and several IFN-inducible genes were up-regulated in these patients ( 50 ).…”

Section: Interferonopathiesmentioning

confidence: 99%

Monogenic Lupus: A Developing Paradigm of Disease

2018

View full text Add to dashboard Cite

Monogenic lupus is a form of systemic lupus erythematosus (SLE) that occurs in patients with a single gene defect. This rare variant of lupus generally presents with early onset severe disease, especially affecting the kidneys and central nervous system. To date, a significant number of genes have been implicated in monogenic lupus, providing valuable insights into a very complex disease process. Throughout this review, we will summarize the genes reported to be associated with monogenic lupus or lupus-like diseases, and the pathogenic mechanisms affected by the mutations involved upon inducing autoimmunity.

show abstract

“…High levels of initial serum ferritin, alveolar-arterial oxygen gradient (P[A-a]O2), and score of ground-glass opacity (GGO) involving the right middle lobe were reported to be poor prognostic factors in anti-MDA5-positive patients [52]. Increased serum IL-6, IL-8 and IL-10 levels were associated with RP-ILD in PM/DM, and high concentrations of IFN-a and soluble CD163, and the upregulation of IFN-inducible genes were reported in anti-MDA5-positive patients [53][54][55][56][57]. These findings suggest the upregulation of the type 1 IFN system via activation of monocytes, macrophages, or other immunocompetent cells in the pathophysiology of anti-MDA5positive dermatomyositis with RP-ILD, although further investigation is needed.…”

Section: Anti-mda5mentioning

confidence: 99%

Clinical significance of myositis-specific autoantibodies

Nakashima

2018

Immunological Medicine

View full text Add to dashboard Cite

To date, increasing numbers of myositis-specific autoantibodies (MSAs) have been reported and their clinical significance has been elucidated. Anti-aminoacyl-tRNA synthetase (ARS) and anti-melanoma-differentiation associated gene 5 (MDA5) are strongly associated with interstitial lung disease (ILD); however, the clinical course of ILD is different depending on which autoantibody is present. Anti-ARS is associated with chronic and repetitive ILD and anti-MDA5 is associated with rapidly progressive ILD. Anti-MDA5, anti-transcriptional intermediary factor (TIF) 1-c, anti-nuclear matrix protein (NXP) 2 and anti-Mi-2 antibodies are dermatomyositis specific. Anti-TIF1-c and anti-NXP-2 antibodies are associated with malignancy, and anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies are associated with immune-mediated necrotizing myopathy (IMNM). Prognosis is also different among MSA-positive patient groups. Thus, MSAs are of great use for predicting disease course, prognosis, and determining therapeutic strategy as well as the diagnosis of idiopathic inflammatory myopathy (IIM) patients. Investigation of the pathogenic role of MSAs and their corresponding autoantigens will help us to understand the pathophysiology of IIM and identify new therapeutic targets. ARTICLE HISTORY

show abstract

Aberrant activation of the type I interferon system may contribute to the pathogenesis of anti‐melanoma differentiation‐associated gene 5 dermatomyositis

Abstract: Our data confirm the aberrant activation of type I IFN system in anti-MDA5 DM. Overproduction of IFN-α linked with BAFF may be implicated in the development of ILD. This article is protected by copyright. All rights reserved.

Cited by 62 publications

References 40 publications

A high level of serum neopterin is associated with rapidly progressive interstitial lung disease and reduced survival in dermatomyositis

A high level of serum neopterin is associated with rapidly progressive interstitial lung disease and reduced survival in dermatomyositis

Monogenic Lupus: A Developing Paradigm of Disease

Clinical significance of myositis-specific autoantibodies

Contact Info

Product

Resources

About