Diagnostic and Predictive Value of an Immune Monitoring Program for Complications after Kidney Transplantation

Abstract

We have tested an immune monitoring program consisting of cytofluorometric analysis of lymphocytic and monocytic markers, using a set of different monoclonal antibodies (mAb), in about 500 transplant patients including about 300 long-term renal allograft recipients. The high sensitivity (95%) of these cytofluorometric analyses in the peripheral blood allows to discriminate between acute rejection and other causes of deteriorated kidney transplant function (infection, toxicity, arteriopathy), especially in the late phase ( > 1 year) after transplantation. Additionally, the immune monitoring is sufficient to predict success of antirejection therapy as early as a few days after onset of treatment. A life-threatening complication in allograft recipients is septic disease. Proceeding from immune parameters, septic patients were found to fall into two categories: those with decreased expression of HLA-DR on monocytes ( < 20%, termed as ‘immunoparalysis’) and patients with nearly normal HLA-DR+ monocytes. Septic immunoparalysis requires drastic reduction of immunosuppression (mortality after drastic reduction: 8%; after marginal reduction or without reduction: 90%). We have not observed severe rejection as a consequence of reduced immunosuppression in such patients. Our immune monitoring seems to be useful for management of immunosuppression in patients with unclear deterioration in graft function as well as patients with septic complications in order to minimize two risks, i.e. death by sepsis or loss of graft.

Critical Illness–Induced Immune Suppression: Current State of the Science

“…Indeed, tapering of doses of these medications can be an important strategy when managing these patients in the ICU. 7,27 It is also important to acknowledge, however, that many medications routinely used in the ICU for other reasons may have immunosuppressive effects. Examples include sedatives, opioids, catecholamines, and some antibiotics.…”

Immunoparalysis and Adverse Outcomes from Critical Illness

“…Among 91 patients, those whose monocyte HLA-DR expression dropped below 30% (n = 48) experienced increased rates of bacteremia, viremia, and fungemia compared to those whose HLA-DR levels remained > 30% (n = 43). Providing additional evidence for the reversibility of immunoparalysis, Reinke et al described a cohort of 45 adult kidney transplant recipients who developed nosocomial sepsis in the setting of immunoparalysis [84]. Patients who underwent rapid tapering of their calcineurin inhibition experienced a 90% survival rate (30/33) with 98% graft survival.…”

Increased CD64 expression on polymorphonuclear neutrophils indicates infectious complications following solid organ transplantation

“…(63)(64)(65)(66)(67). Elevated WBC count and low HLA-DR on monocytes are useful parameters for the detection of infectious complications (26,68), but not for the detection of rejection (26,69). In the literature, an association between leukocytopenia and rejection is declared (70), which was not examined in this study.…”