Clinical Utility of an Enzyme-Linked Immunosorbent Assay for Detecting Anti-Melanoma Differentiation-Associated Gene 5 Autoantibodies.

Abstract

OBJECTIVE:

Autoantibodies to melanoma differentiation-associated gene 5 (MDA5) are specifically expressed in patients with dermatomyositis (DM) and are associated with a subset of DM patients with rapidly progressive interstitial lung disease (RP-ILD). Here, we examined the clinical utility of a newly developed enzyme-linked immunosorbent assay (ELISA) system for detecting these antibodies.

METHODS:

Here we developed an improved ELISA for detecting anti-MDA5 antibodies. We then performed a multicenter clinical study involving 8 medical centers and enrolled 242 adult patients with polymyositis (PM)/DM, 190 with non-PM/DM connective tissue disease (CTD), 154 with idiopathic interstitial pneumonia (IIP), and 123 healthy controls. Anti-MDA5 antibodies in the patients' serum samples were quantified using our newly developed ELISA, and the results were compared to those obtained using the gold-standard immunoprecipitation (IP) assay. In addition, correlations between the ELISA-quantified anti-MDA5 antibodies and clinical characteristics were evaluated.

RESULTS:

In patients with PM/DM, the anti-MDA5 antibody measurements obtained from the ELISA and IP assay were highly concordant; the ELISA exhibited an analytical sensitivity of 98.2%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 99.5% (compared to the IP assay). Anti-MDA5 antibodies were detected in 22.7% of the DM patients, but not in any of the patients with PM, non-PM/DM CTD, or IIP. Clinically amyopathic DM, RP-ILD, arthritis, and fever were more prevalent in DM patients who were anti-MDA5 antibody-positive than in those who were antibody-negative (P ≤ 0.0002 for all comparisons). In addition, anti-MDA5 antibody-positive patients with RP-ILD exhibited higher antibody levels than those without RP-ILD (P = 0.006).

CONCLUSION:

Our newly developed ELISA can detect anti-MDA5 antibodies as efficiently as the gold standard IP assay and has the potential to facilitate the routine clinical measurement of anti-MDA5 antibodies in patients who suspected to have DM.

• Authors: Shinji Sato, Akihiro Murakami, Akiko Kuwajima, Kazuhiko Takehara, Tsuneyo Mimori, Atsushi Kawakami, Michiaki Mishima, Takafumi Suda, Mariko Seishima, Manabu Fujimoto, Masataka Kuwana
• Journal: PloS one (PLoS One) Vol. 11 Issue 4 Pg. e0154285 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 27115353 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• IFIH1 protein, human
• Interferon-Induced Helicase, IFIH1

Topics

• Adult
• Aged
• Autoantibodies (blood)
• Case-Control Studies
• Connective Tissue Diseases (blood, diagnosis, immunology)
• Dermatomyositis (blood, diagnosis, immunology)
• Diagnosis, Differential
• Enzyme-Linked Immunosorbent Assay (standards)
• Female
• Gene Expression
• Humans
• Idiopathic Interstitial Pneumonias (blood, diagnosis, immunology)
• Immunoprecipitation
• Interferon-Induced Helicase, IFIH1 (antagonists & inhibitors, genetics, immunology)
• Male
• Middle Aged
• Polymyositis (blood, diagnosis, immunology)
• Sensitivity and Specificity