Anti-MDA5 autoantibodies associated with juvenile dermatomyositis constitute a distinct phenotype in North America.

Abstract

OBJECTIVE:

Myositis-specific autoantibodies have defined distinct phenotypes of patients with juvenile myositis (JIIM). We assessed the frequency and clinical significance of anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody-associated JIIM in a North American registry.

METHODS:

Retrospective examination of the characteristics of 35 JIIM patients with anti-MDA5 autoantibodies was performed, and differences from other myositis-specific autoantibody groups were evaluated.

RESULTS:

Anti-MDA5 autoantibodies were present in 35/453 (7.7%) of JIIM patients and associated with older age at diagnosis, and lower serum creatine kinase and aldolase levels. Patients with anti-MDA5 autoantibodies had more frequent weight loss, adenopathy, arthritis, interstitial lung disease (ILD), and less frequent falling compared with anti-transcriptional intermediary factor 1 (TIF1), anti-nuclear matrix protein 2 (NXP2) and myositis-specific autoantibody/myositis-associated autoantibody-negative patients. They had a different season of diagnosis and less frequent mechanic's hands and ILD compared with those with anti-synthetase autoantibodies. Anti-MDA5 patients received fewer medications compared with anti-TIF1, and corticosteroid treatment was shorter compared with anti-TIF1 and anti-nuclear matrix protein 2 autoantibody groups. The frequency of remission was higher in anti-MDA5 than anti-synthetase autoantibody-positive JIIM. In multivariable analyses, weight loss, arthritis and arthralgia were most strongly associated with anti-MDA5 autoantibody-positive JIIM.

CONCLUSION:

Anti-MDA5 JIIM is a distinct subset, with frequent arthritis, weight loss, adenopathy and less severe myositis, and is also associated with ILD. Anti-MDA5 is distinguished from anti-synthetase autoantibody-positive JIIM by less frequent ILD, lower creatine kinase levels and differing seasons of diagnosis. Anti-MDA5 has comparable outcomes, but with the ability to discontinue steroids more rapidly and less frequent flares compared with anti-TIF1 autoantibodies, and more frequent remission compared with anti-synthetase JIIM patients.

• Authors: Gulnara Mamyrova, Takayuki Kishi, Min Shi, Ira N Targoff, Adam M Huber, Rodolfo V Curiel, Frederick W Miller, Lisa G Rider, Childhood Myositis Heterogeneity Collaborative Study Group
• Journal: Rheumatology (Oxford, England) (Rheumatology (Oxford)) Vol. 60 Issue 4 Pg. 1839-1849 (04 06 2021) ISSN: 1462-0332 [Electronic] England
• PMID: 33140079 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Published by Oxford University Press on behalf of the British Society for Rheumatology 2020.

Chemical References

• Autoantibodies
• Glucocorticoids
• Creatine Kinase
• IFIH1 protein, human
• Interferon-Induced Helicase, IFIH1
• Fructose-Bisphosphate Aldolase
• Amino Acyl-tRNA Synthetases

Topics

• Age Factors
• Amino Acyl-tRNA Synthetases (immunology)
• Autoantibodies (blood)
• Child
• Creatine Kinase (blood)
• Dermatomyositis (blood, drug therapy, epidemiology)
• Fructose-Bisphosphate Aldolase (blood)
• Glucocorticoids (therapeutic use)
• Humans
• Interferon-Induced Helicase, IFIH1 (immunology)
• Lung Diseases, Interstitial (epidemiology)
• Lymphadenopathy (epidemiology)
• North America (epidemiology)
• Registries
• Retrospective Studies
• Seasons
• Severity of Illness Index
• Weight Loss