Background and Purpose Tripartite motif-containing protein 72 (TRIM72) mediates tissue-repair following injury in several organs, including muscle and lung. Autoantibodies directed against TRIM72 (anti-TRIM72) have been identified in patients with idiopathic inflammatory myopathies (IIM) and disrupt TRIM72 function in vitro. We hypothesized that IIM patients positive for anti-TRIM72 antibodies would have a more severe clinical phenotype.

Methods Sera from IIM patient (antisynthetase syndrome [ASyS], immune mediated necrotizing myopathy [IMNM], and dermatomyositis [DM]) and healthy controls (HC) were included. Anti-TRIM72 autoantibodies were tested using enzyme linked immunosorbent assay. Anti-TRIM72 testing was positive if value was >2 standard deviations above the mean for HC. Clinicodemographic features were identified through chart review and compared between anti-TRIM72 positive (anti-TRIM72[+]) and negative (anti-TRIM72[-]) groups.

Results Anti-TRIM72 levels were significantly increased in patients with ASyS and IMNM when compared to patients with DM and healthy controls. Anti-TRIM72 levels were also increased in patients expressing anti-Jo-1, anti-PL7, anti-HMGCR, anti-SRP, and anti-MDA5. In ASyS, when anti-TRIM72(+) and anti-TRIM72(-) patients were compared, there were significantly more anti-TRIM72(+) ASyS patients with normal DLCO (>75%) when compared to anti-TRIM72(-); however, there were no differences in demographic features, CK levels or FVC. In anti-HMGCR(+) IMNM, anti-TRIM72(+) was associated with a lower proportion of females, as well as older age at time of diagnosis and at time of anti-TRIM72 testing; however, there was no significant difference in other clinicodemographic features in anti-HMGCR(+) IMNM patients when anti-TRIM72(+) and anti-TRIM72(-) groups were compared.

Conclusions Anti-TRIM72 antibody titres are increased in patients with ASyS and IMNM. The presence of anti-TRIM72 antibodies was not associated with a more severe phenotype in ASyS or anti-HMGCR(+) IMNM, and there were more ASyS patients with normal DLCO in the anti-TRIM72(+) group.

E.K. owns stock in MVMD. L.C-S. has research support from Amgen, Pfizer, EMD Serono, and Abcuro. She has served on advisory boards for Abcuro, Allogene, AroBioTx, Boehringer-Ingelheim, BMS, Chugai, IgNS, EMD Serono, Galapagos, Janssen, Mallinckrodt, NKarta, NuVig, Octapharma, Priovant, MBL, Ensho, Steritas, Werfen. She is also a patent holder on an assay for anti-HMGCR auto-antibodies for which she received royalty payments from Inova Diagnostics. J.P. is PI on clinical trials for ArgenX and Priovant.

This research was supported by The Johns Hopkins Rheumatic Disease Research Core Center (P30-AR053503), Buck, Jerome L Greene Foundation, K08AR077100 (BA), K08AR0777732 (ET), R01AR084 (WJ and NW). EK fellowship funding provided through University of Calgary Helios Award and TD Bank Meloche Monnex and Alberta Medical Association Award.

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