Serum interferon-α is a useful biomarker in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis

Horai, Yoshiro; Koga, Tomohiro; Fujikawa, Keita; Takatani, Ayuko; Nishino, Ayako; Nakashima, Yoshikazu; Suzuki, Takahisa; Kawashiri, Shin‐ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Nakamura, Hideki; Ida, Hiroaki; Kakugawa, Tomoyuki; Sakamoto, Noriho; Ishimatsu, Yuji; Mukae, Hiroshi; Hamaguchi, Yasuhito; Fujimoto, Manabu; Kuwana, Masataka; Origuchi, Tomoki; Kohno, Shigeru; Kawakami, Atsushi

doi:10.3109/14397595.2014.900843

Cited by 70 publications

(47 citation statements)

References 20 publications

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“…60,61 These serological characteristics may indicate the activation of monocytes and macrophages in the pathophysiology of anti-MDA5-positive DM with intractable ILD, although other cytokines, such as IL-8, IL-10 and interferon-a are also elevated, suggesting complex mechanisms in the pathophysiology of the disease. [61][62][63] HRCT findings of anti-MDA5-positive patients were reported by Tanizawa et al as an absence of intralobular reticular opacities and a predominance of consolidation and GGO in lower lung fields or random GGO patterns. 37 Because of the very poor prognosis of DM patients who develop RP-ILD, combined immunosuppressive therapy has been recommended.…”

Section: Anti-mda5 Antibodymentioning

confidence: 99%

Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease

Nakashima

Hosono

Mimori

2016

Lupus

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Anti-aminoacyl-tRNA synthetase (ARS) and anti-melanoma differentiation-associated gene 5 ( MDA5) antibodies are closely associated with interstitial lung disease in polymyositis and dermatomyositis. Anti-ARS-positive patients develop common clinical characteristics termed anti-synthetase syndrome and share a common clinical course, in which they respond well to initial treatment with glucocorticoids but in which disease tends to recur when glucocorticoids are tapered. Anti- MDA5 antibody is associated with rapidly progressive interstitial lung disease and poor prognosis, particularly in Asia. Therefore, intensive immunosuppressive therapy is required for anti- MDA5-positive patients from the early phase of the disease. New enzyme-linked immunosorbent assays to detect anti-ARS and anti- MDA5 antibodies have recently been established and are suggested to be efficient and useful. These assays are expected to be widely applied in daily practice.

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Section: Anti-mda5 Antibodymentioning

confidence: 99%

Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease

Nakashima

Hosono

Mimori

2016

Lupus

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“…Several groups have reported an upregulated interferon gene signature in peripheral blood cells of CADM patients with anti-MDA5 positive, rapidly-progressive ILD (24,25). However, it has been difficult to find direct published evidence that the inflamed pulmonary tissue of such patients display evidence of upregulated class I interferon.…”

Section: Interstital Lung Diseasementioning

confidence: 99%

MDA5 autoantibody—another indicator of clinical diversity in dermatomyositis

Sontheimer¹

2017

Annals of Translational Medicine

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Allenbach and colleagues have recently reported for the first time the results of an intriguing study of the histopathologic, immunopathologic and gene expression differences in muscle biopsy tissue from adult dermatomyositis (DM) patients who do and do not have circulating MDA5 autoantibodies (anti-MDA5). Anti-MDA5 were originally identified in a clinically-defined subset of DM patients whose disease was expressed predominately in the skin for unusually long periods of time without accompanying muscle weakness [i.e., "clinically-amyopathic DM" (CADM)] and were at risk for acute, rapidly-progressive form of interstitial lung disease (ILD). As an academic dermatologist in the United States of America (USA) having a career-long interest in the CADM subset, I would like to share my perspective on the results of the work by Allenbach and colleagues and offer some suggestions for additional study in this area. But to do so most effectively, I first would like to review the clinical concept of CADM and its association with anti-MDA5 antibody production and a potentially-fatal form of (ILD).

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“…However, in other studies, this correlation was not observed [21, 23]. Here, the prognostic role of anti-MDA5 antibodies was analyzed for 115 patients that carried anti-MDA5 antibodies and for 250 patients that were negative for anti-MDA5 antibodies.…”

Section: Discussionmentioning

confidence: 84%

“…As shown in Figure 1, fifteen eligible studies were selected for analysis. Of these studies, eight involved cases of PM [6, 8, 10, 11, 13–16], nine involved cases of DM [6, 8, 10, 11, 13–15, 17, 18], six involved cases of classic DM [6, 8, 11, 14–16], ten involved cases of CADM [6, 8, 10, 11, 14–16, 18–20], and six involved mortality [8, 10, 14, 21–23]. The characteristics of each eligible study are summarized in Supplementary Tables 1 and 2.…”

Section: Resultsmentioning

confidence: 99%

Anti-MDA5 antibody as a potential diagnostic and prognostic biomarker in patients with dermatomyositis

Wang

Yang

et al. 2017

Oncotarget

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The presence of anti-MDA5 antibodies in serum represents an important biomarker in the diagnosis and prediction of prognosis for patients with idiopathic inflammatory myopathies (IIMs). Due to conflicting results that have been reported regarding the detection of anti-MDA5 antibodies, the goal of this study was to assess a potential association between the presence of anti-MDA5 antibodies and dermatomyositis/polymyositis (DM/PM), as well as the diagnostic and prognostic values of anti-MDA5 antibodies for DM/PM. For this, a review of literature published prior to October 15, 2016 was conducted. Eight studies with 286 PM patients and 216 healthy controls and nine studies with 628 DM patients and 221 healthy controls were selected according to specific inclusion criteria. The outcomes of these studies revealed that the presence of anti-MDA5 antibodies was associated with DM, especially CADM, and not with PM. Furthermore, the pooled sensitivity, specificity, and area under the curve (AUC) values were 0.62 (95% confidence interval (CI): 0.52–0.70), 1.00 (95% CI: 0.97–1.00), and 0.9381 for CADM patients versus healthy controls when an immunoprecipitation method was used. The presence of anti-MDA5 antibodies was also found to be significantly associated with an increased risk of death in DM (relative risk = 3.32, 95% CI: 1.65–6.67, P = 0.001). These findings suggest that anti-MDA5 antibodies correlate with DM and could be used as a biomarker in the clinical diagnosis of CADM. The presence of anti-MDA5 antibodies was also associated with poor prognosis regarding the overall survival of patients with DM.

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Serum interferon-α is a useful biomarker in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis

Abstract: Serum IFN-α can be used as a useful biomarker in patients with anti-MDA5 Ab-positive DM, which may reflect the presence of RPILD.

Cited by 70 publications

References 20 publications

Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease

Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease

MDA5 autoantibody—another indicator of clinical diversity in dermatomyositis

Anti-MDA5 antibody as a potential diagnostic and prognostic biomarker in patients with dermatomyositis

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