MICA Polymorphism, Association with Diseases and the Role of Anti-MICA Antibodies in Organ and Stem Cell Transplantation

Abstract

Major histocompatibility complex class 1 chain-related genes (MIC) are part of the non-classical MHC genes located on the short arm of chromosome 6. MICA comprises of approximately 11 kb DNA and encodes polypeptide of 383 amino acids. The expression of MICA is limited to the surface of the epithelial cells, fibroblasts, keratinocytes and monocytes, but not on the surface of CD4+, CD8+ and CD19+ lymphocytes. It manifests its role by binding with the NK cell receptor NKG2D. There are 84 different alleles for MICA due to discovered polymorphisms in the exons 2 to 5. The aim of this review is to present the data known so far about the association of MICA with different diseases and the role of anti-MICA antibodies in organ and stem cell transplantation. The frequency of different MICA alleles and their association with different HLA-B alleles, as well as the association of MICA with different inflammatory diseases, infection diseases and tumors was determined. Post- and pre-transplant anti-MICA antibodies are associated with antibody-mediated rejection in kidney and heart transplantation. Patients with hematopoietic stem cell transplantation, which have MICA mismatch, have higher frequency of graft versus host disease episodes. In spite of lack of conclusive data about the role of anti-MICA antibodies in organ and stem cell transplantation, there is still clinical relevance for investigation of the polymorphisms of the MICA gene and anti-MICA antibodies.