Inflammatory Markers and Autoantibodies That Correlate with Early and Late Onset of New Onset Pediatric Chronic Graft-Versus-Host Disease (GVHD).
Notice bibliographique
Résumé
Abstract Chronic graft-vs-host disease (cGVHD) has previously been characterized by elevation of a number of inflammatory markers and autoantibodies. We hypothesized that evaluation of such markers would contribute to a biological classification of new onset cGVHD in children and possibly aid in early diagnosis. The COG study ASCT0031 is a phase III cGVHD therapeutic trial that included the biological evaluation of 52 newly diagnosed cGVHD pts and 34 time-matched post BMT control patients (2 – 18 yrs) with no clinical evidence of cGVHD. Chronic GVHD was divided into an early onset between 3 to 8 mos post BMT (n=37, mean 5.7, range 3 – 8 months ) and late onset ≥9 months post BMT (n=15, mean 14.3, range 9 to 30 months) groups and 34 non-cGVHD controls evaluated at 6 and 12 months. Soluble B-cell activating factor (sBAFF), soluble IL-2 receptor alpha (sIL-2Ralpha), transforming growth factor-beta (TGF-beta), interferon-alpha (IFN-alpha), monocyte chemoattractant protein-1 (MCP-1), IL-6, anti-nuclear antibody (ANA), anti-dsDNA antibody, anti-mitochondrial antibody and anti-cardiolipin antibody were evaluated by sandwich ELISA. We found an increased level of sBAFF in cGVHD patients with both early (7.2± 5.3 vs. 3.7 ± 2.5 ng/mL, p = 0.008, t-test) and late (3.2 ± 2.7 vs. 1.5 ± 0.8 ng/mL, p = 0.04) onset cGVHD compared with controls. Although the anti-dsDNA concentrations were considered to be in the normal range, they were significantly higher in both early (2.4 ± 2.5 vs. 0.1±0.3 IU/mL; p < 0.0001) and late (4.1 ± 3.1 vs. 0.2 ± 0.3 IU/mL; p < 0.0001) cGVHD compared to non-cGVHD controls. We found that early onset cGVHD compared to patients without cGVHD at 6 months had an elevation in sIL-2Ralpha (10.1±5.4 vs. 7.0±3.4 pg/mL; p < 0.0001) but not in late onset cGVHD. ANA, TGF-beta, IFNalpha, IL-6, MCP-1, and anti-cardiolipin antibodies were not associated with new onset cGVHD. Acute GVHD, a major factor for the development of cGVHD, did not correlate with any of the three markers. We found that the ANA (2.3±2.1 vs. 0.9±0.7 absorbance ratio, p = 0.0004) and anti-dsDNA (anti-dsDNA; 3.8±2.9 vs. 2.4±2.5 IU/mL, p = 0.04) were significantly elevated in de novo onset cGVHD patients compared to those with previous acute GVHD. Soluble BAFF and sIL-2Ralpha are associated with Th1 responses and B cell activation/expansion, whereas anti-dsDNA is associated with specific B cell responses. The elevation of sBAFF and sIL-2Ralpha are consistent with both high levels of T cell and B cell activation as part of early cGVHD. The association of later onset cGVHD with only sBAFF and anti-dsDNA suggests that B cell activation is more predominant in that setting and is consistent with our previous observation of an association of cGVHD with activated Toll-like receptor 9 expressing B cells. These findings suggest early and late cGVHD may be classified by different patterns of T and B cell activation. Early onset cGVHD (3–8 mo. Post BMT) Late Onset cGVHD (>=9 mo. post BMT) Marker cGVHD (N=37) No cGVHD at 6 mo. (N=26) p value cGVHD (N=14) No cGVHD at 12 mo. (N=15) p value Anti-dsDNA (IU/mL) 2.4±2.5 0.1±0.3 <0.001 4.1±3.1 0.2 ± 0.3 <0.001 sBAFF (ng/mL) 7.2± 5.3 3.7 ± 2.5 0.008 3.2 ± 2.7 1.5 ± 0.8 0.04 sIL-2Ralpha (pg/mL) 10.1±5.4 7.0±3.4 <0.001 6.9±3.3 5.6±3.7 NS
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 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 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) | 0,001 | 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 ».