How Can We Measure Immunologic Tolerance in Humans?

Abstract

Prevention and treatment of allograft rejection in organ transplant recipients relies primarily on non-antigen-specific immunosuppression, with all its associated potential hazards and costs. Currently, the status of the recipient immune response is measured by monitoring pharmacologic drug levels and clinical/pathologic evaluation of graft function. Development of reliable assays that can measure accurately the status of the immune response not only would help clinicians customize the prescription of immunosuppressive drugs in individual patients but also may allow their complete withdrawal in some patients with immunologic tolerance. Furthermore, these assays would facilitate the safe evaluation of novel tolerogenic regimens. Achieving this goal has proved to be very difficult because it requires both a more in-depth understanding of complex mechanisms of tolerance and also identification of transplant patients with acquired tolerance to an allograft that can be studied. This review discusses the current understanding of tolerance mechanisms and outlines the unique and specific challenges in development of tolerance/monitoring assays in the field of transplantation. In addition, several of the most promising candidate assays are discussed in detail.

Immunosuppression and Regulation

“…If we could only identify these patients, immunosuppression could be stopped or tapered with anticipation of a favorable outcome rather than by trial and error. Indeed, development of assays to identify tolerant recipients are the subject of a review on immunological monitoring by Najafian et al in this issue of JASN (1). Also in this issue, Lopez et al, and other reports noted below, suggest that certain standard immunosuppressive agents may directly promote tolerance through generation of regulatory T cells (Tregs) (2).…”

Individual Stability of Stereotypes of Immune Reacting and Modern Possibilities of Their Diagnostic in Organ Transplantation (Immune-Physiological Analysis of a Problem)

“…В то же время разработка систем надежных пока-зателей по результатам исследования крови продол-жается [39][40][41][42][43][44], так как кровь в клиническом плане наиболее доступная и насыщенная информацион-ная среда, а индустрия современной диагностики имеет практически неограниченные возможности, так как позволяют определить в крови концентра-цию практически любой значимой молекулы [41].…”

The Role of Islet Cell Transplantation in the Management of Diabetes

“…In vitro tests are being developed to dissect the roles of allo-and autoimmunity, often using the enzyme-linked immunosorbent spot (ELISPOT) with human leukocyte antigen (HLA)/islets peptide. 34,35 The many exciting possible strategies for improving the outcome of islet cell transplantation include using rituximab (to prevent the recurrence of autoimmunity), insulin sensitisers (to reduce the negative effect of insulin resistance), and glucagon-like peptide (GLP)-1 analogues (such as exendin or liraglutide), which have islet antiapoptotic and regenerative effects. 36 One of the major limiting factors in islet cell transplantation is the lack of knowledge regarding the fate of the islets following transplantation in the liver.…”