Splicing Factor Proline/Glutamine-Rich Is a Novel Autoantigen of Dermatomyositis and Associated with Anti-Melanoma Differentiation-Associated Gene 5 Antibody.

Yuji Hosono¹, Ran Nakashima¹, Kosaku Murakami¹, Yoshitaka Imura¹, Satoshi Serada², Minoru Fujimoto³, Hajime Yoshifuji¹, Koichiro Ohmura⁴, Tetsuji Naka⁵ and Tsuneyo Mimori⁴, ¹Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan, ²Laboratory for Immune Signal, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan, ³Laboratry of immune signal, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan, ⁴Kyoto University Graduate School of Medicine, Kyoto, Japan, ⁵Laboratory for immune signal, National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: autoantibodies, dermatomyositis, interstitial lung disease, myositis and viruses

Session Information

Date: Sunday, November 13, 2016

Title: Muscle Biology, Myositis and Myopathies - Poster I: Basic/Translational

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

Anti- melanoma differentiation-associated gene 5 (MDA5) antibody positive dermatomyositis (DM) and clinically amyopathic DM (CADM) often develop rapidly progressive interstitial lung disesase (RP-ILD), but the pathogenesis is still unclear. We noticed that the sera from many anti-MDA5 antibody positive patients immunoprecipitated the common 110kDa polypeptide. Thus we intended to identify the autoantigen and investigated the clinical significance.

Methods:

Autoantibodies were screened in 340 patients with various connective tissue diseases (CTDs) and 15 healthy controls (HCs) by immunoprecipitation with [³⁵S]methionine-labeled HeLa cells. Immunoabsorbent column chromatography was used to purify the reactive autoantigen and the polypeptide was analyzed by peptide mass fingerprinting.

Results: Anti-110 kDa antibody was detected in 25 DM/CADM patients but not in patients with other CTDs or HCs. All patients with anti-110 kDa antibody were also positive for anti-MDA5 antibody, and had interstitial lung disease. The corresponding polypeptide was identified as splicing factor proline/glutamine-rich protein (SPFQ). Anti-SFPQ antibody was detected at diagnosis and newly appeared in some patients during the disease course. The onsets of DM/CADM had seasonal patterns and showed two peaks according to the temporal appearance of anti-SFPQ antibody. 67% (8/12) of disease onset of patients who had anti-SFPQ antibody at diagnosis were between August and October, whereas 69% (9/13) of those who had newly appearing anti-SFPQ antibody during the disease course were between January and March.

Conclusion:

We identified the anti-110 kDa antibody as DM/CADM specific autoantibody that recognizes SFPQ in patients who also have anti-MDA5 antibody. The onset of DM/CADM with anti-MDA5 antibody had seasonality according to the appearance time of the antibody to SFPQ, which has a role in innate immune responses. These findings may provide new insights into the pathogenesis of DM/CADM with anti-MDA5 antibody.

Disclosure: Y. Hosono, None; R. Nakashima, None; K. Murakami, None; Y. Imura, None; S. Serada, None; M. Fujimoto, None; H. Yoshifuji, None; K. Ohmura, None; T. Naka, None; T. Mimori, None.

To cite this abstract in AMA style:

Hosono Y, Nakashima R, Murakami K, Imura Y, Serada S, Fujimoto M, Yoshifuji H, Ohmura K, Naka T, Mimori T. Splicing Factor Proline/Glutamine-Rich Is a Novel Autoantigen of Dermatomyositis and Associated with Anti-Melanoma Differentiation-Associated Gene 5 Antibody. [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/splicing-factor-prolineglutamine-rich-is-a-novel-autoantigen-of-dermatomyositis-and-associated-with-anti-melanoma-differentiation-associated-gene-5-antibody/. Accessed .

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