035. CANDIDATE BIOMARKERS IN ANCA-ASSOCIATED VASCULITIS IDENTIFIED USING A PROTEOMIC APPROACH
Notice bibliographique
Résumé
Background: Concentrations of many circulating proteins are elevated during severe, active ANCA- associated vasculitis (AAV). Finding biomarkers associated with milder disease, a more clinically relevant need, has proved challenging. In addition, some biomarkers may be directly affected by glucocorticoids. Methods: 30 patients with AAV participating in a longitudinal cohort were studied. Serum samples from 2 visits were used for this study: i) a visit during active disease and when off prednisone; and ii) a visit approximately 3 months later when in clinical remission and on prednisone. A proteomic platform (SomaLogic) was used to measure more than 1300 circulating proteins simultaneously. Wilcoxon signed rank tests were used to analyze 2000 sub-cohorts of 15 patients each resulting from 1000 permutations, with median P < 0.01 regarded as significant. Results: The cohort included 23 patients with GPA, 5 with EGPA, and 2 with MPA. Mean age was 52, and 18 were female. Thirteen were taking a non-steroid immunosuppressive drug at the time of flare, and 21 afterward. Disease activity was relatively low: physician global assessment of severity on a 0-10 scale had a mean of 3.2 (median 3, range 1-7), and only 7 patients had a “major” manifestation by BVAS/WG. Sixteen proteins were associated with active disease: MMP-12, thrombospondin-4, MIP-5, prolactin, MMP-1, FABP3, CD23/FceR, MDC/CCL22, IL-23, PAPP-A, afamin, seprase, MMP-3, RET, complement factor B, and CD5L. Of 77 proteins previously reported to be associated with active AAV, only one met criteria for a significant association in this study, and only 5 others had median P < 0.05. Conclusion: In a cohort of patients with active but relatively mild AAV, 16 serum proteins were associated with significant change after successful treatment with prednisone. Fifteen of these markers have not been reported in AAV. These proteins, all of which are measurable by commercial immunoassays, are candidates for further study in real-world cohorts of partially-treated patients with AAV and mildly active disease. Disclosures: ReveraGen is a for-profit pharmaceutical company. The three authors who are employees of ReveraGen are identified. The other authors do not have a financial interest in ReveraGen. This work was sponsored by the Vasculitis Clinical Research Consortium and received support from the National Institutes of Health (U54 AR057319, RC1 AR 058303, P60 AR047785, and N01 AI15416) and from ReveraGen.
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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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 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) | 0,000 | 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 ».