Molecular Characterization of Rejection in Solid Organ Transplantation

Abstract

Improved knowledge of the alloimmune repertoire, development and clinical application of new therapeutics, advances in surgical techniques, and effective infection prophylaxis have advanced transplantation to the forefront of modern medicine. This chapter provides an outline of the immune cascade contributing to allograft rejection, emphasizes molecular protocols that have been applied to investigate gene expression, and summarizes molecular correlates of rejection of human kidney, heart, lung, liver, or pancreatic islet cell allografts. The advent of an in vitro assay, PCR, to amplify the nucleic acid sequences has greatly reduced the amount of starting material required for the identification and measurement of mRNAs in biological samples. Cytotoxic T lymphocytes (CTL) destroy target cells via multiple effector mechanisms. Cardiac allograft vasculopathy (CAV) is a form of chronic rejection in which intimal thickening leads to accelerated transplant coronary artery disease. Acute rejection of lung allografts is distinguished by perivas-cular mononuclear cell infiltration of venules and arterioles. Chronic rejection of lung allografts is a major diagnostic and therapeutic challenge and a significant contributor to morbidity and mortality. Nucleic acid-based strategies have proven useful for the detection and quantification of gene expression in the clinic. Global expression profiling with technologies such as microarrays will add to our knowledge and provide further insights into molecular pathways, and several pathways are likely to be responsible for the rejection process. The ultimate objective, personalized medicine for the transplant recipient, is an accomplishable goal.