Collagen and Elastin Degradation Products as Potential Biomarkers for Chronic Graft-Versus-Host Disease (cGVHD).
Notice bibliographique
Résumé
Abstract Abstract 1156 Poster Board I-178 Introduction cGVHD is the main cause of impaired quality of life, morbidity and mortality in patients surviving after allogeneic transplantation. To date, no validated biomarkers for diagnosis and follow-up of cGVHD have been established. Among proposed pathophysiological mechanisms, one involves increased turnover of extracellular matrix components as a result of immune-mediated tissue destruction. We hypothesized that analysis of urinary excretion of degradation peptides from collagen (hydroxylysylpyridinoline [HP] and lysylpyridinoline [LP]) and elastin (desmosine [DES]) using high-sensitivity nano-flow liquid chromatography tandem mass spectrometry (nanoLC-MS/MS) might lead to identification of potential biomarkers in patients with cGVHD. Patients and Methods We elected to compare 3 groups: 16 allogeneic transplant recipients with newly diagnosed or relapsing cGVHD before initiation of systemic immunosuppressive therapy (group A), 13 pts with lymphoma who underwent autologous transplantation, in order to measure the impact of high-dose chemotherapy (group B) and 10 healthy volunteers (group C). Clinical characterization of cGVHD was performed according to NIH criteria. Pts already on glucocorticoids and those with bloodstream infection or proteinuria were excluded. Morning urine samples were collected in fasting subjects, then processed and frozen at -80°C until analysis by nanoLC-MS/MS. Samples were purified using mixed-mode strong cation exchange cartridges, derivatized using propionic anhydride and analyzed with nanoLC-MS/MS. Results Pts with cGVHD (group A) were collected at a median of 229 (107-2966) days post transplant; 8 pts had de novo cGVHD, 8 presented with obvious clinical flare-up and 3 had previously suffered from acute GVHD. cGVHD was mild in 1 (6%), moderate in 8 (50%) and severe in 7 (44%) pts. Affected organs included mouth in 12 pts, skin in 11, liver in 11, eyes in 5, GI tract in 5, joints/fascia in 2, genital tract in 1 and lungs in 1. Thrombocytopenia was present in 4 (25%) pts and eosinophilia in 7 (44%). All transplants had been performed for hematological malignancies, using myeloablative (7 pts) or reduced-intensity conditioning (9 pts). Donors were HLA-identical siblings (13 pts), 10/10 (2 pts) or 9/10 (1 pt) unrelated volunteers. Stem cell source was peripheral blood in all but one pts. Pts from group B were collected at a median of 123 (90-377) days post transplant. As shown in enclosed figure, urinary concentrations of DES and HP in group A and B were similar, but both groups showed a marked increase in levels of these compounds compared to group C (p<0.0001, except HP in group B vs C: p=0.0003). We observed no difference in concentrations of LP, a bone collagen cross-linker, between studied groups. Total and free forms of studied peptides showed excellent correlation. Conclusions We found an increase in the urinary excretion of extracellular matrix components in patients with cGVHD. Our results also suggest that the conditioning regimen has significant early effects on the turnover of elastin and collagen. Prospective sampling in a cohort of allogeneic transplant recipients is currently underway to further elucidate the kinetics and the value of HP and DES as potential biomarkers for cGVHD. Disclosures No relevant conflicts of interest to declare.
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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) | 0,000 | 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 ».