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[Preprint]. 2025 Jul 24:2025.07.23.25332079.
doi: 10.1101/2025.07.23.25332079.

Anti-TRIM72 Autoantibodies in Idiopathic Inflammatory Myopathies

Eugene Krustev  1 , Tiara N Safaei  2 , Daniela Trejo-Zambrano  1 , Lisa Christopher-Stine  1 , Andrew Mammen  1   3 , Julie J Paik  1 , Jemima Albayda  1 , Christopher A Mecoli  1 , Brittany L Adler  1 , Noah Weisleder  4 , Wael Jarjour  5 , Brendan Antiochos  1 , Eleni Tiniakou  1
Affiliations

Anti-TRIM72 Autoantibodies in Idiopathic Inflammatory Myopathies

Eugene Krustev et al. medRxiv. .

Abstract

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.

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Conflict of interest statement

Disclosures 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.

Figures

Figure 1:
Figure 1:. Anti Anti-TRIM72 Antibody Levels Across IIM Subtypes and Antibody Specificities.
A) Anti-TRIM72 levels (AU) in HC, ASyS , IMNM and DM. B) Anti-TRIM72 levels in patients positive for MSA or MAA. Thick dotted line denotes median for each group. Thin dotted line denotes >2 SD cutoff (0.9 AU) above HC. Abbreviations: AMA, antimitochondrial antibodies; Anti-EJ, anti-glycyl tRNA synthetase; anti-HMGCR, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase; anti-Jo-1, anti-histidyl tRNA synthetase; anti-Ku, anti-Ku antigen; anti-MDA5, anti-melanoma differentiation-associated gene 5; anti-Mi2, anti-Mi2 antigen; anti-NXP2, anti-nuclear matrix protein 2; anti-OJ, anti-isoleucyl tRNA synthetase; anti-PL-12, anti-alanyl tRNA synthetase; anti-PL-7, anti-threonyl tRNA synthetase; anti-PM/Scl-100/75, anti-PM/Scl complex (100 and 75 kDa proteins); anti-RNP, anti-ribonucleoprotein; anti-SAE, anti-small ubiquitin-like modifier activating enzyme; anti-SRP, anti-signal recognition particle; anti-TIF1-γ, anti-transcription intermediary factor 1-gamma; anti-TRIM72, anti-tripartite motif containing protein 72; anti-Zo, anti-phenylalanyl tRNA synthetase; AU, arbitrary units; ASyS, antisynthetase syndrome; DM, dermatomyositis; HC, healthy controls; IIM, idiopathic inflammatory myopathy; IMNM, immune mediated necrotizing myopathy; unknown, no identifiable myositis-specific or myositis-associated antibodies.*p<0.05, ***p<0.001, ****p<0.0001.
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