Differential DNA methylation associated with anti-dsDNA autoantibody production in systemic lupus erythematosus
Notice bibliographique
Résumé
Aberrant DNA methylation has been implicated in the pathogenesis of systemic lupus erythematosus (SLE), with less DNA methylation observed in SLE patients compared with healthy controls. We sought to determine whether DNA methylation differences are also associated with anti-dsDNA autoantibody production in SLE. Genomic DNA from peripheral blood leukocytes was isolated from 326 SLE patients, including 158 anti-dsDNA-positive and 168 anti-dsDNA-negative. All SLE cases were female, of European descent, and had never smoked. DNA methylation profiles were initially characterized on a subset of patients ( n = 208, with dsDNA-positive cases matched to dsDNA-negative cases on age and disease duration) using the Illumina HumanMethylation27 Beadchip (27 k chip). Subsequently, all patients ( n = 326) were characterized for the HumanMethylation450 array, and analyses focused on the most strongly associated regions from the 27 k methylation data. Paired t tests were used to identify site-specific methylation differences associated with anti-dsDNA autoantibody production in the initial phase, with P < 1.8 × 10 (Bonferroni corrected) considered statistically significant. Genome regions that demonstrated statistically significant associations with dsDNA status were further assessed using the 450 k methylation data. Overall, less methylation was observed in anti-dsDNA positive patients compared with dsDNA-negative patients. Analysis of the 27 k methylation data demonstrated decreased methylation of a CpG site near SOCS2 ( P = 3.5 × 10 ), an inhibitor of the STAT family of transcription factors, as well as a site near GGT1 ( P = 4.3 × 10 ). In addition, increased methylation of two CpG sites in PRIC285 , a transcriptional co-activator for nuclear receptors, was significantly associated with anti-dsDNA autoantibody production ( P = 1.9 × 10 and 3.4 × 10 ). Subsequent analysis of 114 methylation sites from the 450 k methylation data in these regions demonstrated very strong association with the methylation site cg22764925, located in the 5'-UTR region of GGT1 ( P = 2.8 × 10 ), with an average difference of 7.7% between methylation levels of anti-dsDNA-positive and anti-dsDNA-negative patients. The methylation site cg11738543, and several other CpG sites in the SOCS2 gene, were also associated with anti-dsDNA antibody status ( P = 4.2 × 10 ). These findings suggest that abnormal methylation patterns of specific genes, including GGT1 and SOCS2 , may contribute to autoantibody production in SLE. Studies of DNA methylation and other epigenetic modifications may help elucidate biologic mechanisms involved in the pathogenesis of SLE.
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 | 0,005 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| 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 ».