Anti-Trim72 Autoantibodies in Idiopathic Inflammatory Myopathies
Bibliographic record
Abstract
Objectives The pathogenic mechanisms that underlie the idiopathic inflammatory myopathies (IIM) are complex and not well understood. Triparite motif-containing protein 72 (TRIM72) is expressed in the sarcolemma and mediates membrane-repair following muscle injury.[1] Autoantibodies directed against TRIM72 (anti-TRIM72) have been identified in IIM patients.[2] Anti-TRIM72 autoantibodies may contribute to disease pathogenesis by disrupting the endogenous repair functions of TRIM72.[2] The aim of this study was to investigate the anti-TRIM72 expression and associated clinical characteristics in IIM patients. Methods Sera from patients meeting a clinical diagnosis of IIM patients (dermatomyositis [DM], antisynthetase syndrome [ASyS], immune-mediated necrotizing myopathy [IMNM]) and healthy controls (HC) were included. Anti-TRIM72 autoantibodies were tested using enzyme-linked to immunosorbent assay. Anti-TRIM72 testing was positive if normalized value was >2 standard deviations above the mean for healthy controls. Maximum CK and lowest recorded DLCO were identified through retrospective chart review. One-way ANOVA and Student’s T test were used to compare groups. Results There were 523 IIM patients (ASyS, n=200; IMNM, n=198; DM, n=125) and 67 HC included. Mean anti-TRIM72 levels were significantly increased in patients with ASyS and IMNM when compared to patients with DM and healthy controls (1-way ANOVA, p<0.0001) (Figure 1A). There were 82 ASyS patients had available clinical data and 17.1% (n=14) were anti-TRIM72 positive. When CK values were assessed in patients with ASyS, there was no significant difference between anti-TRIM72 positive patients when compared to those who were negative (difference 1027U/L, 95% CI −1711 to 3765) (Figure 1B). When mean diffusion capacities (lowest DLCO %) were compared between anti-TRIM72 positive and negative ASyS patients, there was no significant difference between groups (difference 5.0%, 95% CI −9.5 to 19.5) (Figure 1C). In patients with IMNM, 14.0% were anti-TRIM72 positive (13/93). There was no significant difference in peak CK when anti-TRIM72 positive and negative IMNM patients (difference −913.9, 95% CI −6097 to 4270) (Figure 1D). Figure 1: Anti-TRIM72 Titres and Association with CK and DLCO in IIM. A) Anti-TRIM72 levels were increased in ASyS patients when compared to DM patients (mean difference 0.65, 95%CI 0.4032 to 0.8940) and HC (mean difference 0.67, 95%CI 0.36 to 0.97). Patients with IMNM had significantly higher anti-TRIM72 titres when compared to those with DM (mean difference 0.44, 95%CI 0.19 to 0.69) and HC (mean difference 0.46, 95%CI 0.15 to 0.76). There was no significant difference when patients with DM were compared to HC (mean difference 0.02, 95%CI −0.31 to 0.35). B) In patients with ASyS, there was a no significant difference in peak CK (U/L) between anti-TRIM72 positive and negative patients (difference 1027, 95%CI −1711 to 3765). In patients with ASyS, there was no significant difference in lowest recorded DLCO (%) between anti-TRIM72 positive and negative patients (difference 5.0,95%CI −9.5 to 19.5). In patients with IMNM, there was no significant difference in peak CK (U/L) between anti-TRIM72 positive and negative patients (difference −913.9, 95%CI −6097 to 4270). Abbreviations: ASyS, antisynthetase syndrome; CK, creatine kinase; DLCO, diffusing capacity of the lungs for carbon monoxide; DM, dermatomyositis; HC, healthy control; IIM, idiopathic inflammatory myopathy; IMNM, immune mediated necrotizing myopathy; TRIM, tripartite motif-containing protein 72. Conclusion Anti-TRIM72 autoantibodies are expressed in a subset of patients with both ASyS and IMNM. Previous studies have suggested a pathogenic role in IIM; however, further studies are needed to understand the clinical manifestations and utility of these autoantibodies. [1.] Cai C. Biophys J 2009:96(3);361a. [2.] McElhanon KE. J Clin Invest 2020:130(8);4440-55.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".