A Lesson of Immunosuppression in Renal Transplant: Retreat or Hold?

Background: Aiming at understanding whether there are cases of near-tolerance among long-term surviving kidney transplant recipients in our center, or even operant tolerance can be attempted based on their immune status, we analyzed changes of immune cell subsets and cytokines in various groups, and evaluated immune status of long-term survival recipients. Methods: A real-world, observational, retrospective cohort study was conducted in our hospital. Twenty-eight long-term recipients were selected as study subjects, 15 recent postoperative stable recipients, and 15 healthy subjects as controls. T and B lymphocyte subsets, MDSCs, and cytokines were detected and analyzed. Results: Treg/CD4 T cells, total B and B10 cells in long-term and recent renal recipients were lower than healthy controls (HC). The level of IFN-γ and IL-17A in long-term survival patients was obviously higher than that in recent postoperative stable recipients and HC, while TGF-ß1 level was significantly lower in long-term survival group than in short-term postoperative group and HC. Notably, compared with short-term recipients, it has been found that the IL-6 level in both positive and negative HLA groups were obviously lower (all P<0.05). In the long-term survival group, 43% of recipients were positive for urinary protein and 50% were positive for HLA antibody. Conclusion: This "real-world" study validates the findings of real status of long-term survival recipients observed in clinical trials. Contrary to a state of proper tolerance as expected, the group recipients in long-term survival were accompanied by the increased indicators of immune response, while those related to immune tolerance were not significantly increased. Long-term survival recipients with stable renal function may be in an immune equilibrium state where immunosuppression and rejection coexist under the action of low-intensity immune agents. If immunosuppressive agents are reduced or even removed, rejection may occur.

Lymphocyte function based on IFN-γ secretion assay may be a promising indicator for assessing different immune status in renal transplant recipients.

BACKGROUND: Immunological monitoring plays a crucial role in organ recipients for allowing tailoring of immunosuppression. However, there is still a paucity of promising indicators for detecting immune status in recipients. METHODS: We conducted a prospective study to characterize the immune status by detecting dynamically lymphocyte subsets and function (represented by the abilities to secrete IFN-γ) in the first 6 months posttransplant in renal recipients. Participants were classified into an immune stable group, infected group, and rejected group. RESULTS: In the stable group, our study suggested that the counts and function of CD4+ T, CD8+ T, and NK lymphocytes decreased to their nadir at week 2, and thereafter these indicators were gradually restored. The counts exceeded pre-operative levels, whereas function did not reach the pre-transplant levels by 6 months. We demonstrated that function of lymphocytes was considerably decreased in infected recipients compared with the stable group when infection occurred. By contrast, the function of lymphocytes was obviously increased at the point of rejection. Receiver operating characteristic (ROC) analysis in the combination of subsets and function of lymphocytes presented a superior clinical value with an area under the curve (AUC) of 0.903 in the diagnosis of infected receivers, and IFN-γ+CD8+ T cells% is the highest indicator with the auROC curve of 0.862. Another ROC analysis confirmed that IFN-γ+CD4  T cells% presented a preferable diagnostic value with an area of 0.887 for rejected recipients. CONCLUSIONS: In conclusion, the ability of lymphocyte subsets secreting IFN-γ may provide a promising assessment of immune status in recipients and allow timely modifying immunosuppression.