IMMUNE PARAMETERS IN THREE DUCHENNE MUSCULAR DYSTROPHY PATIENTS FOLLOWING INTRAMUSCULAR TRANSPLANTATION OF NORMAL MYOGENIC CELLS UNDER FK506 IMMUNOSUPPRESSION.
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".