Plasma Levels of Soluble Interleukin-7 Receptor Alpha (sIL-7Ra) and IL-7Ra Polymorphism After Allogeneic Stemcell Transplantation,
Notice bibliographique
Résumé
Abstract Abstract 4012 Background: Interleukin-7 (IL-7) is a cytokine essential for T cell development in the thymus and maintenance of peripheral T cells. IL-7 binds to cellular IL-7 receptors (IL-7Ra-common g chain heterodimer), in competition with a soluble form of the receptor, shed by the cells (sIL-7Ra). We have identified single nucleotide polymorphisms in the exons of the gene encoding IL-7Ra (+510T/C rs1494558, +1237 G/C rs1494555, 2087 C/T rs6897932), and previous results by us and by others indicate that IL-7R SNPs are associated with aGvHD and mortality after SCT. Moreover, the biological significance of +2087 C/T SNP has been suggested by the finding of elevated serum levels of sIL-7Ra in healthy individuals with 2087CC (Haplotype 4), also associated with increased alternative splicing of exon 6 and a higher frequency of recent thymic emigrants. We hypothesized that sIL-7Ra levels during SCT are influenced by genetic polymorphism and may play a role in immune reconstitution after SCT. Aims: 1) To investigate sIL-7Ra levels during SCT along with IL-7Ra genotypes and 2) to evaluate associations between sIL-7Ra levels and immune reconstitution and outcome in SCT. Patients and Methods: 122 patients undergoing SCT for haematological malignancies after either myeloablative (n= 52) or reduced intensity conditioning (n=70) were included. Donors were either matched siblings (n=68) or matched unrelated donors (n=54), and the patient age at the time of transplant was 50 years (6–67) (median (range)). sIL-7Ra levels were measured in plasma by a quantitative bead capture assay. IL-7Ra SNPs were determined by a SSP-PCR system and IL-7 was tested by ELISA (R&D) (n=77). Results: sIL-7Ra levels decreased during the course of transplantation from 113 ng/ml (32–558) at day −15 to 48 ng/ml (32–195) at day +14 (p=0.0001), and reached baseline levels again at day +60. sIL-7Ra levels were not associated with the intensity of the conditioning regimen. This pattern appeared to be inversely mirrored by the IL-7 levels, which increased from baseline values at day –14 of 2.4 pg/ml (0.3–17.6) to 11.3 pg/ml (2.0–30.2) (p<0.0001) at day +14, followed by a gradual decline down to baseline values at day +60. sIL-7Ra levels at day +90 were reduced in patients transplanted with donors carrying IL-7Ra 2087T allele, in line with our previous findings in healthy individuals (105 ng/ml (42–274) vs. 152 ng/ml (20–971), p=0.0015). In addition, post-transplant sIL-7Ra levels correlated with pre-transplant sIL-7Ra levels (r=0.39 p=0.0032), indicating that patient related factors in addition to the genotype of the donor lymphocytes may play a role in the regulation of sIL-7Ra levels post-transplant. sIL-7Ra appeared to be predictive of the rate of immune reconstitution by the finding that sIL-7Ra at day +14 correlated significantly with total lymphocyte counts post-transplant (day +90: r=0.28 (p=0.031) and day +180: r=0.55 (p<0.0001)). In contrast, IL-7Ra genotypes were not associated with immune lymphocyte counts post-transplant and early post-transplant IL-7 levels did not correlate significantly with lymphocyte counts at any stage. Outcomes: There was a trend towards an association between high sIL-7Ra levels and increased overall survival (p=0.057), but sIL-7Ra levels were unrelated to the occurrence of aGvHD. However, the IL-7/sIL-7Ra ratio at day +14 was significantly higher in patients with grade 2–4 aGvHD compared to grade 0–1 aGvHD (0.29 (0.04–0.73) vs 0.19 (0.01–0.8), p=0.033). Conclusion: The data of the present study indicates that sIL-7Ra levels after SCT are determined by the IL-7R 2087 genotype of the donor in addition to patient related factors. sIL-7Ra levels in the early phase post transplant is associated with the rate of lymphocyte recovery post-SCT. Thereby this study adds to the growing evidence suggesting the importance of the IL-7 axis in SCT. The study further suggests that monitoring sIL-7Ra levels post-transplant may help to guide the clinical use of IL-7. 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 | 0,000 | 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) | 0,001 | 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 ».