Background/Purpose:

Anti-melanoma differentiation-associated gene 5 (MDA5) autoantibodies are common among Japanese dermatomyositis (DM) and clinically amyopathic DM (CADM) patients who develop rapidly progressive interstitial lung disease (RP-ILD). Recently, autoantibodies recognizing the 100 kDa splicing factor proline/glutamine-rich (SFPQ) were discovered to co-exist in half of Japanese anti-MDA5-positive DM patients. Anti-SFPQ autoantibodies were often absent in initial serum samples but appeared later during the course of disease and in a seasonal pattern. Anti-MDA5-positive patients with anti-SFPQ autoantibodies were older and had a higher prevalence of mechanic’s hands than those without the co-existing autoantibodies. To date, anti-SFPQ autoantibodies have not been described in anti-MDA5-positive patients outside of Japan. Thus, the purpose of this study was to identify the prevalence and clinical significance of anti-SFPQ autoantibodies among anti-MDA5-positive DM patients in a cohort of DM patients from the United States.

Methods:

We included all anti-MDA5-positive DM patients enrolled in a longitudinal cohort study at the Johns Hopkins Myositis Center. Anti-SFPQ autoantibodies were detected in patient serum samples collected at the first and most recent visits by immunoprecipitating radioactively-labeled proteins from [³⁵S]-methionine-labeled HeK cells. The identities of immunoprecipitated proteins were confirmed by peptide mass fingerprinting.

Results:

Fifty-five anti-MDA5-positive DM/CADM patients were included in this study. From among these, autoantibodies recognizing the 100kDa autoantigen were detected in 4 (7.3%) of the DM/CADM patients. The corresponding polypeptide was confirmed to be SPFQ by mass spectrometry. Among the 4 patients with co-existing anti-MDA5 and anti-SFPQ autoantibodies, 1 was also positive for anti-U1-RNP autoantibodies and 1 was anti-Ro52-positive. All anti-SFPQ autoantibodies were detected at the time of first visit to the Johns Hopkins Myositis Center rather than appearing later during the disease course. 75% (3/4) of the anti-SFPQ antibody positive patients at initial symptom onset in March-April, and all had ILD; one of these died from severe ILD. The remaining patient had diagnosis in October and did not have ILD.

Conclusion:

Although more than half of Japanese anti-MDA5-positive DM patients eventually have co-existing anti-SFPQ autoantibodies, only 7.3% of anti-MDA5-positive DM patients in this United States cohort were positive for anti-SFPQ autoantibodies. These findings highlight an important difference between anti-MDA5-positive DM/CADM patients in the United States and Japan.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-splicing-factor-proline-glutamine-richautoantibodies-rarely-co-exist-with-anti-melanoma-differentiation-associated-gene-5-autoantibodies-in-a-cohort-of-dermatomyositis-patients-from-the-united-st/