Anti-MDA5 and anti-TIF1-γ antibodies have clinical significance for patients with dermatomyositis

Kei Hoshino, Yoshinao Muro, Kazumitsu Sugiura, Yasushi Tomita, Ran Nakashima, Tsuneyo Mimori

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

Objectives. Myositis-specific autoantibodies are useful for diagnosing PM/DM. Recently, two new myositis-specific autoantibodies against melanoma differentiation-associated gene 5 (MDA5) and transcriptional intermediary factor 1-γ (TIF1-γ) were identified in DM. Here, we detected these autoantibodies in patient sera using new assays with recombinant MDA5 and TIF1-γ, and associated clinical features with the presence of anti-MDA5 or anti-TIF1-γ antibodies. Methods. We screened 135 Japanese patients with various CTDs, including 82 with DM. DM patients were classified as clinically amyopathic DM (CADM), cancer-associated DM or classical DM without cancer. Anti-MDA5 and anti-TIF1-γ antibodies were detected by their ability to immunoprecipitate biotinylated recombinant proteins.Results. Sera from 21 (26%) of 82 DM patients immunoprecipitated MDA5, and every anti-MDA5-positive patient had DM (except one patient with SSc). Sera from 20 (65%) of 31 CADM patients reacted with MDA5. Notably, anti-MDA5-positive DM patients had significantly more interstitial lung disease than anti-MDA5-negative DM patients (95 vs 32%, P < 0.001). Sera from 12 (15%) of 82 DM patients immunoprecipitated TIF1-γ, and anti-TIF1-γ antibodies were only detected in DM patients. Strikingly, 7 (58%) of 12 patients with cancer-associated DM had sera that reacted with TIF1-γ. Anti-TIF1-γ-positive DM patients had significantly more internal malignancies than anti-TIF1-γ-negative DM patients (58 vs 9%, P < 0.001).Conclusions. Anti-MDA5 and anti-TIF1-γ antibodies were confirmed to be serological DM subset markers. Anti-MDA5 and anti-TIF1-γ antibodies were detected based on their ability to immunoprecipitate biotinylated recombinant MDA5 and TIF1-γ, and were closely associated with life-threatening complications in DM.

Original languageEnglish
Article numberkeq153
Pages (from-to)1726-1733
Number of pages8
JournalRheumatology
Volume49
Issue number9
DOIs
Publication statusPublished - 25-05-2010

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Dermatomyositis
Melanoma
Antibodies
Genes
Autoantibodies
Serum
Myositis
transcriptional intermediary factor 1
Neoplasms
Interstitial Lung Diseases
Recombinant Proteins

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Pharmacology (medical)

Cite this

Hoshino, Kei ; Muro, Yoshinao ; Sugiura, Kazumitsu ; Tomita, Yasushi ; Nakashima, Ran ; Mimori, Tsuneyo. / Anti-MDA5 and anti-TIF1-γ antibodies have clinical significance for patients with dermatomyositis. In: Rheumatology. 2010 ; Vol. 49, No. 9. pp. 1726-1733.
@article{77a57d9b9e5442afabfeccabb8fae975,
title = "Anti-MDA5 and anti-TIF1-γ antibodies have clinical significance for patients with dermatomyositis",
abstract = "Objectives. Myositis-specific autoantibodies are useful for diagnosing PM/DM. Recently, two new myositis-specific autoantibodies against melanoma differentiation-associated gene 5 (MDA5) and transcriptional intermediary factor 1-γ (TIF1-γ) were identified in DM. Here, we detected these autoantibodies in patient sera using new assays with recombinant MDA5 and TIF1-γ, and associated clinical features with the presence of anti-MDA5 or anti-TIF1-γ antibodies. Methods. We screened 135 Japanese patients with various CTDs, including 82 with DM. DM patients were classified as clinically amyopathic DM (CADM), cancer-associated DM or classical DM without cancer. Anti-MDA5 and anti-TIF1-γ antibodies were detected by their ability to immunoprecipitate biotinylated recombinant proteins.Results. Sera from 21 (26{\%}) of 82 DM patients immunoprecipitated MDA5, and every anti-MDA5-positive patient had DM (except one patient with SSc). Sera from 20 (65{\%}) of 31 CADM patients reacted with MDA5. Notably, anti-MDA5-positive DM patients had significantly more interstitial lung disease than anti-MDA5-negative DM patients (95 vs 32{\%}, P < 0.001). Sera from 12 (15{\%}) of 82 DM patients immunoprecipitated TIF1-γ, and anti-TIF1-γ antibodies were only detected in DM patients. Strikingly, 7 (58{\%}) of 12 patients with cancer-associated DM had sera that reacted with TIF1-γ. Anti-TIF1-γ-positive DM patients had significantly more internal malignancies than anti-TIF1-γ-negative DM patients (58 vs 9{\%}, P < 0.001).Conclusions. Anti-MDA5 and anti-TIF1-γ antibodies were confirmed to be serological DM subset markers. Anti-MDA5 and anti-TIF1-γ antibodies were detected based on their ability to immunoprecipitate biotinylated recombinant MDA5 and TIF1-γ, and were closely associated with life-threatening complications in DM.",
author = "Kei Hoshino and Yoshinao Muro and Kazumitsu Sugiura and Yasushi Tomita and Ran Nakashima and Tsuneyo Mimori",
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Anti-MDA5 and anti-TIF1-γ antibodies have clinical significance for patients with dermatomyositis. / Hoshino, Kei; Muro, Yoshinao; Sugiura, Kazumitsu; Tomita, Yasushi; Nakashima, Ran; Mimori, Tsuneyo.

In: Rheumatology, Vol. 49, No. 9, keq153, 25.05.2010, p. 1726-1733.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Anti-MDA5 and anti-TIF1-γ antibodies have clinical significance for patients with dermatomyositis

AU - Hoshino, Kei

AU - Muro, Yoshinao

AU - Sugiura, Kazumitsu

AU - Tomita, Yasushi

AU - Nakashima, Ran

AU - Mimori, Tsuneyo

PY - 2010/5/25

Y1 - 2010/5/25

N2 - Objectives. Myositis-specific autoantibodies are useful for diagnosing PM/DM. Recently, two new myositis-specific autoantibodies against melanoma differentiation-associated gene 5 (MDA5) and transcriptional intermediary factor 1-γ (TIF1-γ) were identified in DM. Here, we detected these autoantibodies in patient sera using new assays with recombinant MDA5 and TIF1-γ, and associated clinical features with the presence of anti-MDA5 or anti-TIF1-γ antibodies. Methods. We screened 135 Japanese patients with various CTDs, including 82 with DM. DM patients were classified as clinically amyopathic DM (CADM), cancer-associated DM or classical DM without cancer. Anti-MDA5 and anti-TIF1-γ antibodies were detected by their ability to immunoprecipitate biotinylated recombinant proteins.Results. Sera from 21 (26%) of 82 DM patients immunoprecipitated MDA5, and every anti-MDA5-positive patient had DM (except one patient with SSc). Sera from 20 (65%) of 31 CADM patients reacted with MDA5. Notably, anti-MDA5-positive DM patients had significantly more interstitial lung disease than anti-MDA5-negative DM patients (95 vs 32%, P < 0.001). Sera from 12 (15%) of 82 DM patients immunoprecipitated TIF1-γ, and anti-TIF1-γ antibodies were only detected in DM patients. Strikingly, 7 (58%) of 12 patients with cancer-associated DM had sera that reacted with TIF1-γ. Anti-TIF1-γ-positive DM patients had significantly more internal malignancies than anti-TIF1-γ-negative DM patients (58 vs 9%, P < 0.001).Conclusions. Anti-MDA5 and anti-TIF1-γ antibodies were confirmed to be serological DM subset markers. Anti-MDA5 and anti-TIF1-γ antibodies were detected based on their ability to immunoprecipitate biotinylated recombinant MDA5 and TIF1-γ, and were closely associated with life-threatening complications in DM.

AB - Objectives. Myositis-specific autoantibodies are useful for diagnosing PM/DM. Recently, two new myositis-specific autoantibodies against melanoma differentiation-associated gene 5 (MDA5) and transcriptional intermediary factor 1-γ (TIF1-γ) were identified in DM. Here, we detected these autoantibodies in patient sera using new assays with recombinant MDA5 and TIF1-γ, and associated clinical features with the presence of anti-MDA5 or anti-TIF1-γ antibodies. Methods. We screened 135 Japanese patients with various CTDs, including 82 with DM. DM patients were classified as clinically amyopathic DM (CADM), cancer-associated DM or classical DM without cancer. Anti-MDA5 and anti-TIF1-γ antibodies were detected by their ability to immunoprecipitate biotinylated recombinant proteins.Results. Sera from 21 (26%) of 82 DM patients immunoprecipitated MDA5, and every anti-MDA5-positive patient had DM (except one patient with SSc). Sera from 20 (65%) of 31 CADM patients reacted with MDA5. Notably, anti-MDA5-positive DM patients had significantly more interstitial lung disease than anti-MDA5-negative DM patients (95 vs 32%, P < 0.001). Sera from 12 (15%) of 82 DM patients immunoprecipitated TIF1-γ, and anti-TIF1-γ antibodies were only detected in DM patients. Strikingly, 7 (58%) of 12 patients with cancer-associated DM had sera that reacted with TIF1-γ. Anti-TIF1-γ-positive DM patients had significantly more internal malignancies than anti-TIF1-γ-negative DM patients (58 vs 9%, P < 0.001).Conclusions. Anti-MDA5 and anti-TIF1-γ antibodies were confirmed to be serological DM subset markers. Anti-MDA5 and anti-TIF1-γ antibodies were detected based on their ability to immunoprecipitate biotinylated recombinant MDA5 and TIF1-γ, and were closely associated with life-threatening complications in DM.

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