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Trans-vivo Delayed Type Hypersensitivity Assay for Antigen Specific Regulation
Published on: May 2, 2013
Longitudinal analysis of T-helper cell phenotypes in renal-transplant recipients undergoing growth hormone therapy
Anette Melk1, Volker Daniel, Otto Mehls
1Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany. anette.melk@med.uni-heidelberg.de
Insights
Recombinant human growth hormone (rhGH) therapy in pediatric renal transplant recipients shows a mild, temporary immune stimulation. Careful monitoring of immunosuppression and graft function is recommended during rhGH treatment.
Area of Science:
- Pediatric Nephrology
- Immunology
- Endocrinology
Background:
- Recombinant human growth hormone (rhGH) is effective for growth-retarded children post-renal transplant.
- Concerns exist regarding rhGH's potential immunomodulatory effects.
- This study investigates rhGH's impact on immune phenotypes in pediatric renal transplant recipients.
Purpose of the Study:
- To evaluate immune phenotypes in pediatric renal transplant recipients receiving rhGH.
- To assess potential shifts toward a T-helper (TH)1-type immune response.
- To determine the safety and immunomodulatory effects of rhGH in this population.
Main Methods:
- Four-color flow cytometry was used to analyze intracellular cytokines and activation markers.
- 13 children post-renal transplant (Tx+GH) were studied during rhGH therapy.
- Control groups included children with chronic renal failure (CRF+GH) and transplant recipients without rhGH (Tx).
Main Results:
- rhGH therapy transiently increased IL-2, IL-4, and IL-13 levels in Tx+GH patients within 12 weeks.
- Cytokine levels returned to baseline by 18 weeks; no graft rejection occurred.
- CRF+GH patients showed higher baseline cytokines that did not change with rhGH therapy.
Conclusions:
- rhGH therapy induces a mild and transient immunostimulatory effect in stable pediatric renal transplant recipients.
- Close monitoring of immunosuppression and graft function is crucial for patients on rhGH.
- The findings suggest rhGH is safe in the short term but requires careful follow-up.
Background:
Treatment with recombinant human growth hormone (rhGH) in growth-retarded children after renal transplantation is effective, but there have been concerns regarding the safety of rhGH because of its possible immunomodulatory actions. We therefore evaluated the immune phenotypes of pediatric renal-transplant recipients and controls in response to rhGH with regard to a possible shift toward a T-helper (TH)1-type response.
Methods:
Intracellular cytokines, activation markers, costimulatory, and adhesion molecules were studied in 13 children after renal transplantation (Tx+GH). Children with chronic renal failure (CRF+GH, n=11) before and under rhGH therapy and pediatric renal-transplant recipients without rhGH therapy (Tx, n=33) served as controls. Measurements were performed by four-color flow cytometry before and 4, 12, 18 and 24 weeks after initiation of rhGH therapy.
Results:
Under baseline conditions, Tx+GH patients did not differ from Tx patients. During rhGH therapy in children with transplants, interleukin (IL)-2 production increased threefold at 4 weeks, and IL-4 and IL-13 increased by 70% at 12 weeks. All three cytokines returned to baseline after 18 weeks. No patient experienced rejection. In CRF+GH patients, baseline values for all investigated cytokines were higher than in patients with transplants but did not change in response to rhGH therapy.
Conclusion:
Our data indicates that rhGH therapy in stable, pediatric renal-transplant recipients has a mild and transient immunostimulatory effect in vivo. Immunosuppression and graft function in patients with transplants undergoing rhGH treatment should therefore carefully be monitored.
