RESUMEN
This experimental study assessed the impact of medications frequently used after kidney transplantation on the immune system of pregnant female Wistar rats. The study evaluates medications, both approved and contraindicated during pregnancy in common therapeutic combinations. The study was conducted on 32 female Wistar rats, subjected to immunosuppressive regimens most commonly used in therapy of human kidney transplant recipients (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; and cyclosporine A, everolimus and prednisone). The animals received drugs by oral gavage 2 weeks before pregnancy and at 3 weeks of pregnancy. We found drug regimen-dependent differences in cytometry from spleen. Many subpopulations of lymphocytes were suppressed in rats treated with cyclosporine A, mycophenolate mofetil and prednisone and tacrolimus, mycophenolate mofetil and prednisone; the number of NK cells was increased in group of rats treated with cyclosporine A, everolimus and prednisone. We also found changes in histological examination of thymus and spleen of all treated dams. In cytokine assay, we noticed increasing levels of IL-17 with increasing doses of concanavalin A in control group and in group of dams treated with cyclosporine A, mycophenolate mofetil and prednisone. This increase was blocked in rats treated with tacrolimus, mycophenolate mofetil and prednisone and cyclosporine A, everolimus and prednisone. Qualitative, quantitative and morphological changes of immune system in pharmacologically immunosuppressed females have been observed. Thymus structure, spleen composition and splenocytes IL-17 production were mostly affected in drug regimen-dependent manner.
Asunto(s)
Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Células Asesinas Naturales/inmunología , Embarazo/efectos de los fármacos , Bazo/efectos de los fármacos , Timo/efectos de los fármacos , Administración Oral , Animales , Femenino , Humanos , Terapia de Inmunosupresión , Interleucina-17/metabolismo , Embarazo/inmunología , Ratas , Ratas Wistar , Bazo/inmunología , Timo/inmunologíaRESUMEN
BACKGROUND: Blood products infusions are often administrated to graft recipients. Post-transfusion reactions of anti-human leukocyte antigen antibodies (anti-HLA) are responsible for transfusion-related acute lung injury, but cases of graft rejection after blood product infusions were recently also proven. METHODS: The aim of this study was to assess, with the use of the very sensitive Luminex technology and traditional lymphocytotoxic test, the prevalence and cytotoxic activity of anti-HLA in blood donors with different medical histories to evaluate a potential risk of post-transfusion immune complications. Data were analyzed according to different normalized background cutoffs (1.5, 2.2; and the high cutoffs-10.8 for I class and 6.9 for II class anti-HLA). RESULTS: We observed that anti-HLA may be present in 36% of donors, and even in up to 73.6% of risk groups. Significant risk factors included female sex (23.9% to 64.2% for different cutoffs) and pregnancy history (30% to 72.5%), regardless of the cutoff used in analysis, whereas sera from female donors showed lower cytotoxicity (panel reactive antibodies). Anti-HLA were also detected in men (3.7% to 37%), in donors after a transfusion (0% to 62.5%), and even with no known risk factors (3.8% to 26.9%). CONCLUSIONS: Luminex technology is a sensitive tool in anti-HLA detection, but consensus in measurement interpretation for blood donors is needed. Selection of blood products on the basis of medical history can be a useful alternative for routine testing of blood donors. The clinical significance of treatment of graft recipients with blood products requires further study; until then, more attention should be paid to possible complications.