The Impact of Graft-Versus-Host Disease on Dendritic Cell Homeostasis and Their Potential Use As Biomarker to Predict the Severity of Chronic Graft-Versus-Host Disease
Notice bibliographique
Résumé
Abstract PURPOSE: Graft-versus-host disease (GVHD) is the principal complication of allogeneic stem cell transplantation (allo-SCT) and occurs when GVHD T cells recognize differences in major and/or minor histocompatibility antigens expressed by recipient cells. Following cytotoxic regimens, the inflammatory milieu represents a fertile ground for alloreactivity and thymic insults resulting from GVHD are largely responsible for thymic dysfunction and immune-incompetence. Studies have also demonstrated that GVHD insult to the peripheral niche is perhaps the most important factor for limiting thymic independent T cell regeneration. Given that patients with chronic GVHD (cGVHD) are profoundly lymphopenic and that dendritic cells (DCs) play a critical role in T cell homeostasis, we postulated that changes in DC counts could precede the development of clinical signs of acute and/or chronic GVHD. METHODS: 44 patients that received HLA-matched allogeneic SCT were included in this study. Controls consist of 15 patients that received autologous SCT and 30 healthy donors. Flow cytometric analysis was used to measure plasmacytoid DCs (pDCs), myeloid DC type 1 (mDC1), mDC2 and mDC3. Blood samples were obtained at day 0, 1 month post-SCT and then every other month until 1 year. The percentage and absolute counts of naïve CD4+ or CD8+ lymphocytes (TNA); (CD3+ CD45RA+ CCR7+), central memory (TCM); (CD3+ CD45RA+ CCR7neg), effector memory (TEM); (CD3+ CD45RAneg CCR7neg) and terminal differentiation (TTD); (CD45RA+ CCR7neg) was determined by flow cytometry. B lymphocytes and regulatory CD4+ T cells were also evaluated. RESULTS: One month after allo-SCT, we found a significant increase in blood DCs followed by a gradual decrease and stabilization by 3 months post-allo-SCT. During the first year, all DC subsets including pDCs, mDC1, mDC2, mDC3 as well as CD4+ and CD8+ T cells were significantly diminished compared to autologous and healthy controls. Plasmacytoid DCs regeneration was in general the most affected and we found a positive correlation between pDC cells count and the number of naïve and central memory CD4+ lymphocytes. Similarly, pDCs counts also correlated with the number of naïve and memory CD8+ T cells. In contrast, effector CD4+ and CD8+ T cell showed a stronger correlation with mDC1. Patients with grade II-IV acute GVHD had lower DC counts compared with mild grade 0-1 aGVHD and a similar trend was also observed during the development of cGVHD, Importantly, loss of pDCs and mDC1 that preceded the development of cGVHD by 1 month was associated with the development of grade 3 cGVHD whereas loss of DCs during cGVHD was associated with milder 0-2 cGVHD. Thus far, our data support a model wherein loss of pDCs and mDC1 could represent potential biomarkers to predict the severity of cGVHD. Disclosures No relevant conflicts of interest to declare.
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 | 0,001 | 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 ».