EPIGENETIC PROFILING OF CHILDHOOD-ONSET LUPUS REVEALS DISTINCT EPIGENETIC CLUSTERS AND SUGGESTS EPIGENETIC DRIVERS OF DISEASE ACTIVITY
Notice bibliographique
Résumé
PV110 / #608 Poster Topic: AS12 - Genetics, Epigenetics, Transcriptomics Background/Purpose Systemic lupus erythematosus, or lupus, is a chronic autoimmune disease that can affect multiple organ systems. Childhood-onset lupus is typically associated with a more severe disease course compared to adult-onset lupus. DNA methylation alterations play an important role in the pathogenesis of lupus. We have previously demonstrated a higher genetic risk for lupus in childhood-onset compared to adult-onset disease. However, epigenetic studies in childhood-onset lupus have been limited. The aim of this study was to investigate DNA methylation changes in childhood-onset lupus. Methods A total of 64 patients with childhood-onset lupus and 47 healthy controls from Turkey were included in this study. DNA from peripheral blood mononuclear cells (PBMCs) was isolated to assess DNA methylation patterns using the Infinium MethylationEPIC v2.0 array (Illumina). Quality controls and statistical analyses were performed using minfi and limma R packages. Methylation differences among groups were tested through linear regression, adjusting for age, sex, medication use, and cell subset compositions. Differences in clinical manifestations were assessed using Fisher’s exact tests. Gene ontology (GO) enrichment analyses were performed with the online tools Metascape and GREAT. Results Case-control differential DNA methylation analysis revealed significant hypomethylation in interferon-regulated genes, such as DTX3L, PARP9, IFI44L , and MX1 , in patients compared to controls. The enrichment analysis confirmed the presence of type I interferon signature-related biological processes, consistent with our previous findings in adult-onset lupus. The association of DNA methylation levels and disease activity in lupus, as measured by SLEDAI scores, revealed progressive hypomethylation in genes related to B cell activation and cellular senescence as the disease becomes more active. K-means clustering analysis of lupus patients based on DNA methylation patterns identified 3 distinct lupus clusters. Cluster 1 was characterized by the enrichment of hypomethylated genes involved in cell adhesion and response to growth factor pathways; Cluster 2 exhibited hypomethylation in genes related to regulation of cell differentiation and cell fate determination; and Cluster 3 showed enrichment in response to oxidative stress and Rap1 signaling pathway in hypomethylated genes. Conclusions We identified significant hypomethylation in interferon-regulated genes, consistent with the type I interferon epigenetic signature observed in adult-onset lupus. Furthermore, the relationship between DNA methylation changes and disease activity, particularly in genes associated with B cell activation and cellular senescence, suggests that these alterations may play a role in disease progression. The identification of distinct DNA methylation clusters also underscores the heterogeneity of childhood-onset lupus, offering potential avenues for personalized therapeutic strategies. These findings emphasize the need for further investigation into the epigenetic mechanisms driving childhood-onset lupus to improve diagnosis and treatment approaches.
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 source (Gemma direct ou Codex distillé), 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 ».