1708 Preliminary data on the mapping of anti-mitochondrial antibodies in systemic lupus erythematosus
Bibliographic record
Abstract
<h3>Background</h3> In systemic lupus erythematosus (SLE), mitochondria and their inner components may be released into the extracellular space, potentially eliciting a pro-inflammatory response by the immune system. While cardiolipin was long known as a mitochondrial target of autoantibodies, we reported in previous case-control studies that autoantibodies to whole mitochondria (AwMA), mitochondrial DNA (AmtDNA) and mitochondrial RNA (AmtRNA) are also targeted by SLE autoantibodies. We aim to characterize levels of these autoantibodies throughout SLE disease progression. <h3>Methods</h3> Anti-mitochondrial antibodies (AMA, IgGs) targeting whole mitochondria (AwMA), mtDNA (AmtDNA) or mtRNA (AmtRNA) were measured by direct-ELISA, using sera from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. Samples comprised healthy controls (n=127) and 3453 samples obtained from 816 SLE patients, between the diagnosis up to 7 years afterward. Institution of the SLICC cohort obtained approval from their local research ethic boards and written consent from every participant. Eligibility to the cohort, within 15 months of diagnosis, was conditional to the positivity to 4, or more, ACR criteria for the classification of SLE. AMA levels are expressed as the median optical density measured at 405 nm ± interquartile range. Differences in AMA levels between healthy donors and baseline SLE samples were assessed, using Mann-Whitney tests and Spearman tests were used to assess correlations between levels of the various AMA. <h3>Results</h3> Preliminary results indicate that, among the various subsets of IgGs targeting mitochondrial components, AwMA and AmtRNA but not AmtDNA were significantly increased in newly diagnosed SLE patients, in comparison with healthy individuals (respectively: p=0.004, p<0.0001, and p=0.1. figure 1). While AwMA levels remain constant for two years into the disease (Enrollment: 0.11±1.37), an increase is observed after the third year (year 3: 0.17±0.67). A similar effect is measured for AmtRNA levels (Enrollment: 0.21±2.46. Year 3: 0.36±1.81). AwMA levels are correlated to those of AmtDNA and AmtRNA (p<0.0001. Respectively r<sub>s</sub>=0.32 and r<sub>s</sub>=0.38) and levels of both anti-mitochondrial nucleic acids displayed stronger correlations (p<0.0001; r<sub>s</sub>=0.55). <h3>Conclusions</h3> Levels of circulating autoantibodies to whole mitochondria and mtRNA at baseline allow discriminating between healthy individuals and SLE patients. While levels of AMA appear to be fluctuating throughout the disease, further biostatistical analyses will be performed to assess associations between AMA and clinical manifestations and outcomes of the disease. These data will allow to appreciate the quality of AMA as biomarkers in the prediction of clinical outcomes, damages, or the clustering of patients in SLE. <h3>Acknowledgments</h3> Dr. Paul R. Fortin’s (PRF) work is supported by a Canada Research Chair. This study was supported by Canadian Institutes of Health Research (CIHR) grants to PF and Dr. Éric Boilard (EB). Yann LC Becker and EB are recipients of awards from the <i>Fond de Recherche en Santé du Québec</i> (FRSQ).
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".