Background and aims Anti-MDA5-positive dermatomyositis (DM) and clinically amyopathic DM (CADM) often develop rapidly progressive interstitial lung disease, but their pathogenesis remain unclear. We observed that sera from anti-MDA5- positive DM/CADM patients immunoprecipitated a common 110 kDa polypeptide. We investigated the autoantigen and its clinical significance.

Methods Autoantibodies were screened in 340 patients with various connective tissue diseases (CTDs) and 20 healthy controls (HCs) by immunoprecipitation with [³⁵S]methionine-labelled HeLa cells. Immunoabsorbent column chromatography was used to purify the reactive autoantigen which was subsequently analysed by peptide mass fingerprinting.

Results Anti-110 kDa was detected in sera from 25 DM/CADM patients with anti-MDA5 but not in those from other CTDs or HCs. All anti-MDA5-positive DM/CADM patients who showed the recurrence symptoms had anti-110kDa. Interestingly, all who required plasma exchange were not positive for anti-110kDa at the initial plasma exchange. The corresponding autoantigen was identified as splicing factor proline/glutamine-rich protein (SPFQ). In some cases, anti-SFPQ was detected at the diagnosis (early-group), but in other cases, it appeared during the disease course (delayed-group). The diagnosis time of DM/CADM had seasonal patterns according to the temporal appearance of anti-SFPQ antibody. 67% (8/12) of patients were diagnosed between August and October in the early-group, whereas 58% (7/13) of patients were between January and March in the delayed-group.

Conclusions SFPQ is a novel autoantigen of anti-MDA5-positive DM/CADM. The diagnosis timing of DM/CADM with anti-MDA5 have seasonal patterns according to the appearance timing of anti-SFPQ. These findings may provide new insights into the pathogenesis of DM/CADM.