1708 Preliminary data on the mapping of anti-mitochondrial antibodies in systemic lupus erythematosus
Notice bibliographique
Résumé
<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).
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».