Value of circulating immune parameters in renal transplantation

Abstract

Diagnosis of acute kidney graft rejection is based on conventional parameters such as creatinine (Crea), Crea-clearance, body temperature, urinary volume, body weight. Taken together they are inexpensive, noninvasive and attain a relatively high sensitivity. In many patients, however, kidney biopsies have to be obtained to ascertain the presence of acute rejection. The presence or absence of rejection might also be authenticated by monitoring serum immune parameters, capable of predicting the onset of clinically relevant immunologic activity. This would provide information on the response to antirejection therapy before graft dysfunction becomes clinically manifest. The following parameters were selected based on their specific characteristics: • ⊎ c-ICAM-1 (intercellular adhesion molecule). Allograft transplantation leads to a chronic or acute immune response that is related to increased expression and release of c-ICAM-1. c-ICAM-1 is expressed on almost all cell types, including macrophages, T- and B-lymphocytes during activation, as well as unstimulated vascular endothelial cells. Healthy individuals show a mean serum level of 230 (130 to 300) ng/mL. • ⊎ s-TNF-R (tumour-necrosis-factor receptor). Elevated s-TNF-R levels are observed in any type of immune response but also eventuate in acute or chronic renal failure as a retention phenomenon. s-TNF-R binds with high affinity and specificity to TNF and acts as an immunobiological regulator of the pluripotent TNF-mediated functions. The complete receptor molecule is expressed on fibroblasts, endothelial cells (EC), myeloid cells, as well as on mitogen-stimulated lymphocytes. • ⊎ s-IL2-R (interleukin-2-receptor). Monoclonal antibodies to IL2-R inhibit T-cell proliferation and counteract renal allograft rejection. IL2-R-bearing cells are crucial in graft rejection, and agents that kill these cells boost graft survival: anti-IL2-R antibodies administered prophylactically to renal allograft patients reduce the rate of early graft rejection. Its mean level in normal individuals is 256 ± 112 U/mL. • ⊎ Neopterin. Is significantly related to T-cell-mediated pathologies and, therefore, can provide clinically useful information on infection, cancer, autoimmunity and graft rejection. Neopterin release from renal epithelial cells has been shown to be stimulated by IFN-γ. Its mean serum level in normal individuals is 5.4 ± 2.3 nmol/L. • ⊎ s-MHC-1 (major histocompatibility complex). Consists of a 44,000-kD intracellular and a short extracellular polypeptide chain designated β2-microglobulin (β2-MG). MHC-1 is the receptor for CD8 + cytotoxic T cells, with the amount of MHC products apparently determining the susceptibility of target cells to being lysed. • ⊎ ELAM-1 (endothelial leukocyte adhesion molecule). Is a glycoprotein (E-selectin) expressed on cytokine-activated (TNF-alpha, IL2, LPS) endothelial cells. Endothelial cells constitute the interface between allograft and the host's immune system. Endothelial cell functions play a pivotal role in inflammatory responses and vessel behaviour, and might assume a pathogenic role in allograft rejection. E-selectin is the most likely mediator of initial lymphocyte binding to endothelial cells by mediating, in contrast to the integrins, adhesion of resting lymphocytes. The ligands for ELAM-1 are carbohydrates. The present study was performed to establish (1) potential correlations of these parameters with the course of rejection, infection, or of stable condition, in renal allograft recipients and (2) whether antirejection therapy is capable of influencing these parameters. As noninvasive methods for measuring target-organ levels of cytokines or inflammatory markers are not available, a critical appraisal of the sensitivity and specificity of these parameters in peripheral blood during graft rejection appears warranted.