IMMUNE PARAMETERS IN THREE DUCHENNE MUSCULAR DYSTROPHY PATIENTS FOLLOWING INTRAMUSCULAR TRANSPLANTATION OF NORMAL MYOGENIC CELLS UNDER FK506 IMMUNOSUPPRESSION.
Notice bibliographique
Résumé
P678* Aims: To test the efficacy of FK506 immunosuppression to control acute rejection in the context of myoblast allotransplantation in Duchenne muscular dystrophy (DMD) patients. Methods: Three DMD patients received injections of myoblasts obtained from skeletal muscle biopsies of normal donors. The cells (30 x 106) were injected in 1 cm3 of the Tibialis anterior by 25 parallel injections. Similar patterns of saline injections were performed in the contralateral muscles. The patients received FK506 for immunosuppression, the doses being adjusted to maintain a blood concentration between 8 to 20 μg/L. Periodical monitoring of the patients included weight, hemogram, glycemia, lipid profile and serum levels of creatinine, urea, sodium, potassium and chlorides. Patients 1 and 2 were previously taking deflazacort to delay the progression of the disease and we maintained this treatment during the study. Muscle biopsies were performed at the injected sites 4 weeks later. Histological studies were done to analyze the success of the graft, and to characterize the immune cells present in the tissue. RT-PCR analysis of the biopsies were done to observe the expression of INF-gamma, TNF-alpha, granzyme B, IL-6 and FasL. The presence of antibodies against the donor cells in blood samples taken before and at 2, 4 and 8 weeks after cell transplantation was analyzed by cytofluorometry. Results: We observed dystrophin-positive myofibers in the cell-grafted sites of the three patients: 9 % (patient 1), 6.8 % (patient 2), and 11 % (patient 3). Since patients 1 and 2 had identified dystrophin-gene deletions, these results were obtained using monoclonal antibodies specifically to the deleted exons. The grafted site exhibited some pockets of leukocyte infiltration composed of macrophages and CD4+ and CD8+ lymphocytes in patient 1. In patient 2, similar leukocyte infiltrations were smaller and scarce. No leukocyte accumulations were observed in patient 3. No antibodies against the donor-cells and the donor MHC class-I and class II were detected in the 3 cases. Only the IL-6 mRNA was significantly increased in one grafted site (patient 1). The only potential side effect of the immunosuppression was some weight increase in patient 3. Conclusions: Significant dystrophin expression can be obtained in the skeletal muscles of DMD patients following specific conditions of cell delivery and immunosuppression. Only the presence of some macrophage/T-lymphocyte accumulations in the vicinity of dystrophin-positive myofibers, and an increase in IL-6 expression could suggest to a moderate, non-completely controlled cellular acute rejection in patient 1. For the rest, the immunosuppression seems quite appropriate. Since patients 1 and 2 received chronic corticosteroid therapy, an additive effect of this treatment on the FK506-based immunosuppression is perhaps possible. The long-term benefit of a FK506-based immunosuppression for myoblast transplantation in DMD patients remains to be tested.
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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 ».