Krustev Eugene, Safaei Tiara N, Trejo-Zambrano Daniela, Christopher-Stine Lisa, Mammen Andrew, Paik Julie J, Albayda Jemima, Mecoli Christopher A, Adler Brittany L, Weisleder Noah, Jarjour Wael, Antiochos Brendan, Tiniakou Eleni
Johns Hopkins University School of Medicine, Baltimore, MD.
Johns Hopkins Department of Chemical and Biomolecular Engineering, Baltimore, MD.
medRxiv. 2025 Jul 24:2025.07.23.25332079. doi: 10.1101/2025.07.23.25332079.
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 . 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.
含三联基序蛋白72（TRIM72）在包括肌肉和肺在内的多个器官损伤后的组织修复中发挥介导作用。在特发性炎性肌病（IIM）患者中已鉴定出针对TRIM72的自身抗体（抗TRIM72），其会破坏TRIM72的功能。我们推测抗TRIM72抗体阳性的IIM患者会有更严重的临床表型。
纳入IIM患者（抗合成酶综合征[ASyS]、免疫介导的坏死性肌病[IMNM]和皮肌炎[DM]）及健康对照（HC）的血清。采用酶联免疫吸附测定法检测抗TRIM72自身抗体。若检测值高于HC平均值2个标准差以上，则抗TRIM72检测为阳性。通过病历审查确定临床人口统计学特征，并在抗TRIM72阳性（抗TRIM72[+]）和阴性（抗TRIM72[-]）组之间进行比较。
与DM患者和健康对照相比，ASyS和IMNM患者的抗TRIM72水平显著升高。表达抗Jo-1、抗PL7、抗HMGCR、抗SRP和抗MDA5的患者抗TRIM72水平也升高。在ASyS中，比较抗TRIM72（+）和抗TRIM72（-）患者时，抗TRIM72（+）的ASyS患者中DLCO正常（>75%）的比例显著高于抗TRIM72（-）的患者；然而，在人口统计学特征、肌酸激酶水平或用力肺活量方面无差异。在抗HMGCR（+）的IMNM中，抗TRIM72（+）与女性比例较低以及诊断时和抗TRIM72检测时年龄较大相关；然而，比较抗TRIM72（+）和抗TRIM72（-）组时，抗HMGCR（+）的IMNM患者在其他临床人口统计学特征上无显著差异。
ASyS和IMNM患者的抗TRIM72抗体滴度升高。在ASyS或抗HMGCR（+）的IMNM中，抗TRIM72抗体的存在与更严重的表型无关，且抗TRIM72（+）组中DLCO正常的ASyS患者更多。
