NOVEL IgG AND IgA AUTOANTIBODIES IN TWO INDEPENDENT COHORTS ASSOCIATE WITH GLOBAL AND ORGAN-SPECIFIC DISEASE ACTIVITY IN SYSTEMIC LUPUS ERYTHEMATOSUS: IMPLICATIONS FOR ANTI-LIN28A AND ANTI-IRF5
Notice bibliographique
Résumé
O050 / #258 Topic: AS20 - Precision Medicine ABSTRACT CONCURRENT SESSION 08: RECENT ADVANCES IN LUPUS BIOMARKERS 23-05-2025 1:40 PM - 2:40 PM Background/Purpose Autoantibodies are a hallmark of systemic lupus erythematosus (SLE), but among a multitude of autoantigen specificities, few are mapped and used in routine clinical practice. Autoantibodies currently used for surveillance, such as anti-dsDNA, show only modest associations with SLE disease activity. The aim of this study was to identify and validate novel autoantibodies that reflect global and organ-specific disease activity in systemic lupus erythematosus (SLE). Methods Serum samples were screened for IgG and IgA seroreactivity against 1609 protein autoantigens using an immunome microarray (Sengenics). We determined differentially abundant autoantibodies (daAAbs) in SLE patients vs healthy controls within a discovery (n=199 vs n=111) and an independent validation cohort (n=30 vs n=84) from the European PRECISESADS project (NTC02890121). Validated daAAbs were analyzed in relation to global and organ-specific disease activity using linear and logistic regression, along with daAAb target pathway enrichment analysis. Results We validated 89 IgG and 66 IgA daAAbs. IgG anti-LIN28A, IgG anti-HMGN5, and both isotypes for anti-IRF5 and anti-TGIF1 were associated with a SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥10, negatively associated with Lupus Low Disease Activity State (LLDAS), and highly prevalent in patient subgroups with active disease across organ manifestations. IgG anti-LIN28A levels exceeded the cut-off for positivity in 53% of patients with CNS involvement, a prevalence higher than that observed for anti-dsDNA (20%), and 47% of patients with renal activity. A cluster of IgG and IgA daAAbs against RNA-binding proteins, including anti-LIN28A, was predominantly represented in patients with CNS activity. IgA anti-FOSL2 was associated with musculoskeletal activity. Enriched pathways related to DNA binding and repair exhibited considerable overlap across organ systems. Conclusions This study identified and validated novel IgG and IgA autoantibodies. Among those, IgG anti-LIN28A, IgG anti-HMGN5, and both isotypes for anti-IRF5 and anti-TGIF1 were associated with high disease activity and were highly prevalent in subgroups of patients with active disease across organ manifestations. IgG anti-LIN28A levels exceeded the cut-off for positivity in more than half of the patients with CNS involvement, a prevalence higher than that observed for the routine clinical marker anti-dsDNA, and almost half of the patients with renal activity. Additionally, IgG and IgA LIN28A formed autoantibody clusters predominantly represented in patients with CNS activity. The findings of IgA seroreactivity are novel and point to the importance of mucosal immunity in SLE, while the overall findings have direct implications for the early identification of patients with active or evolving disease, and for timely and informed therapeutic intervention.
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 | 0,000 |
| 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 | 0,000 | 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 ».