Immune monitoring as prerequisite for transplantation tolerance trials

• Published in: Clinical and experimental immunology Vol. 189; no. 2; pp. 158 - 170
• Main Authors: Behnam Sani, K., Sawitzki, B.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.08.2017; John Wiley and Sons Inc
• Subjects: Adoptive transfer; Animals; Assaying; B cell; Biomarkers; Chimerism; Clinical trials; Drug development; Graft rejection; Graft Survival; Grafting; Humans; Immune system; Immunological tolerance; Immunology; Immunoregulation; Immunosuppressive agents; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Kidney transplantation; Liver; Liver Transplantation; Lymphocytes T; Monitoring; Monitoring, Immunologic - methods; natural killer cells; Organs; Patients; regulatory T cells; Review; Side effects; Survival; tolerance/suppression/anergy; Transplantation; Transplantation Tolerance; Transplantation, Homologous; Transplants & implants; regulatory T cells; B cell; natural killer cells; transplantation; tolerance/suppression/anergy
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.12988

Summary Ever since its first application in clinical medicine, scientists have been urged to induce tolerance towards foreign allogeneic transplants and thus avoid rejection by the recipient's immune system. This would circumvent chronic use of immunosuppressive drugs (IS) and thus avoid development of IS‐induced side effects, which are contributing to the still unsatisfactory long‐term graft and patient survival after solid organ transplantation. Although manifold strategies of tolerance induction have been described in preclinical models, only three therapeutic approaches have been utilized successfully in a still small number of patients. These approaches are based on (i) IS withdrawal in spontaneous operational tolerant (SOT) patients, (ii) induction of a mixed chimerism and (iii) adoptive transfer of regulatory cells. Results of clinical trials utilizing these approaches show that tolerance induction does not work in all patients. Thus, there is a need for reliable biomarkers, which can be used for patient selection and post‐therapeutic immune monitoring of safety, success and failure. In this review, we summarize recent achievements in the identification and validation of such immunological assays and biomarkers, focusing mainly on kidney and liver transplantation. From the published findings so far, it has become clear that indicative biomarkers may vary between different therapeutic approaches applied and organs transplanted. Also, patient numbers studied so far are very small. This is the main reason why nearly all described parameters lack validation and reproducibility testing in large clinical trials, and are therefore not yet suitable for clinical practice. This review provides an overview of criteria and examples of biomarker characteristic for tolerant transplant patients.