Comprehensive assessment of myositis-specific autoantibodies in polymyositis/dermatomyositis-associated interstitial lung disease

Hozumi, Hironao; Fujisawa, Tomoyuki; Nakashima, Ran; Johkoh, Takeshi; Sumikawa, Hiromitsu; Murakami, Akihiro; Enomoto, Noriyuki; Inui, Naoki; Nakamura, Yutaro; Hosono, Yuji; Imura, Yoshitaka; Mimori, Tsuneyo; Suda, Takafumi

doi:10.1016/j.rmed.2016.10.019

Cited by 147 publications

(123 citation statements)

References 44 publications

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“…Anti-ARS-positive patients develop common clinical manifestations, characterized by myositis, ILD, arthritis, fever, Raynaud's phenomenon and mechanic's hand, which is called 'anti-synthetase syndrome (ASS)' [22]. Anti-ARSs have a strong association with ILD because 70-95% of anti-ARS-positive patients [21,23,24] have ILD and 40-55% of PM/DM patients with ILD are positive for anti-ARSs [2,25]. Anti-ARS-positive ILD tends to be diagnosed at the same time or even before the development of myositis [22].…”

Section: Anti-arsmentioning

confidence: 99%

Clinical significance of myositis-specific autoantibodies

Nakashima

2018

Immunological Medicine

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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

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Section: Anti-arsmentioning

confidence: 99%

Clinical significance of myositis-specific autoantibodies

Nakashima

2018

Immunological Medicine

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“…Although these two factors are considered as serological indicators reflecting the activity of ILD, serum levels of KL-6 and SP-D sometimes dissociate. 8 Collectively, there was no significant difference in the prevalence and severity of ILD between the anti-MDA5 Ab-and anti-ARS Ab-positive groups at baseline. Additionally, the serum levels of ferritin among anti-MDA5 Ab-positive patients was low enough to indicate good prognosis.…”

Section: Discussionmentioning

confidence: 76%

“…7 Indeed, almost half of the ILD patients with anti-MDA5 Ab die within 3 months. 8 However, the predicting factor of RPILD other than anti-MDA5 Ab positivity has not yet been elucidated. 9 Preliminary reports have suggested early introduction of intensive immunosuppressive therapy as a promising strategy for anti-MDA5 Ab-positive patients, 10 but its safety and efficacy have not yet been established.…”

Section: Introductionmentioning

confidence: 99%

Combined immunosuppressive therapy provides favorable prognosis and increased risk of cytomegalovirus reactivation in anti‐melanoma differentiation‐associated gene 5 antibody‐positive dermatomyositis

Matsuda

Yoshizaki

Kuzumi

et al. 2020

The Journal of Dermatology

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Anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab) is myositis-specific autoantibody associated with rapidly progressive interstitial lung disease (ILD) and poor prognosis. In this retrospective observational study, we aimed to verify the efficacy and safety of introducing combined immunosuppressive therapy for anti-MDA5 Ab-positive dermatomyositis (DM) from their early stage. We recruited all Japanese patients diagnosed with DM in our clinic between January 2011 and October 2018, who had anti-MDA5 Ab, anti-aminoacyl transfer RNA synthetase Ab or anti-transcriptional intermediary factor 1-c Ab. Combined immunosuppressive therapy was defined as combination of systemic corticosteroids, i.v. cyclophosphamide and tacrolimus. The difference of clinical features among the three groups was analyzed by multiple comparison analysis. The longitudinal change of the measurements from baseline was examined by Wilcoxon signed-rank test. Association between therapeutic regimens and adverse events was examined by logistic regression analysis. As a result, combined immunosuppressive therapy was most frequently used in the anti-MDA5 Ab-positive group, which significantly improved their forced vital capacity of the lung. Interval time since initial visit until starting treatment was the shortest in the anti-MDA5 Ab-positive group. There was no significant difference in the incidence of death and recurrence among the three groups. Cytomegalovirus reactivation was most common in the anti-MDA5 Ab-positive group, associated with combined immunosuppressive therapy. Collectively, early introduction of combined immunosuppressive therapy was effective for DM patients with anti-MDA5 Ab. At the same time, clinicians should be aware of the risk of cytomegalovirus reactivation during the treatment.

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“…The presence of anti-ARS antibody including anti-PL-7 antibody has been reported to be associated with a favorable response to immunosuppressive therapy and an increased overall survival in PM/DM patients with ILD (27-29). However, it has been suggested that the clinical phenotype and prognosis vary with the type of anti-ARS antibody in patients with ASS.…”

Section: Discussionmentioning

confidence: 99%

Anti-PL-7 Antisynthetase Syndrome with Eosinophilic Pleural Effusion

et al. 2018

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A 68-year-old woman was admitted to our hospital with fever and pleural effusion. Her thoracentesis showed eosinophilic pleural effusion (EPE) without any evidence of malignancy, infection, or trauma. Pleural biopsy revealed pleuritis and intercostal myositis. Characteristic skin manifestations, including Gottron's sign, interstitial lung disease, and pericardial effusion, appeared later in the clinical course. She was finally diagnosed with anti-PL-7 antisynthetase syndrome (ASS) based on the presence of anti-PL-7 antibody, and she fulfilled the diagnostic criteria for dermatomyositis. These clinical manifestations improved with immunosuppressive therapy. EPE might therefore be one of the characteristic features of anti-PL-7 ASS.

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Comprehensive assessment of myositis-specific autoantibodies in polymyositis/dermatomyositis-associated interstitial lung disease

Cited by 147 publications

References 44 publications

Clinical significance of myositis-specific autoantibodies

Clinical significance of myositis-specific autoantibodies

Combined immunosuppressive therapy provides favorable prognosis and increased risk of cytomegalovirus reactivation in anti‐melanoma differentiation‐associated gene 5 antibody‐positive dermatomyositis

Anti-PL-7 Antisynthetase Syndrome with Eosinophilic Pleural Effusion

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