Impaired cellular immune function in patients with end-stage renal failure

Abstract

Patients with chronic renal failure are at high-risk for activation in renal failure patients. Obviously, there infectious complications, similar to patients with other are also alterations of antigen-unspecific immune mech- types of acquired immune defects or those on immuno- anisms, e.g. phagocyte function, but these will not be suppressive therapy. Secondary immune failure in discussed here. The original observation of reduced uraemia is multi-faceted and is influenced by uraemic responses to hepatitis B vaccination (1) was comple- intoxication per se, by altered renal metabolism of mented by documentation of hyporesponsiveness to immunologically active proteins and by specific eVects other vaccines such as tetanus or diphtheria. Non of renal replacement therapy. Large interindividual response to vaccination is closely associated with an variability points to the importance of individual fac- impaired proliferation of T-cells in vitro and a reduced tors. A high incidence of infection is found in uraemic production of the autocrine T-cell growth promoting patients and infections remain the second most fre- cytokine interleukin-(IL-)2 (2,3). Activation of helper quent cause of death. T-cells is needed for both cellular and antibody One specific problem is hepatitis B. Vaccination responses to T-cell-dependent antigens such as those against hepatitis B is routinely performed in dialysis tested in the vaccination trials. Only a few antigens patients. Although eVective in only 60-70% of patients, lead to T-cell independent production of antibodies it helped to eliminate the threat of hepatitis B from by B-lymphocytes, among them highly polymeric bac- dialysis centres. The response to hepatitis B vaccine terial antigens, for instance Pneumococcal vaccine. proved to be a valid clinical index for individual Vaccination responses to Pneumococcus vaccine are immune reactivity in dialysis patients. normal in renal failure patients. These findings focused interest on T-cell activation as a crucial step to explain defective antigen specific immune responses in patients Cellular dysfunction: a defect of the antigen- with renal failure. presenting cell Lymphocyte numbers as well as the CD4/CD8 rela- tion are slightly diminished in dialysis patients, but Low response rates after vaccination against hepatitis these findings cannot explain reduced T-cell function. B lead to several studies on antigen-specific immune Although functional data suggested a defect of the T-lymphocytes, cell behaviour was entirely normal when activated in vitro in the presence of antigen-