Chapter 17 - The human leukocyte antigen system in human disease and transplantation medicine

Abstract

Major histocompatibility complex (MHC) represents the most polymorphic gene dense region of the human genome, which reflects several inherent features. Based on its evolving biological relevance in health and disease, the human leukocyte antigen (HLA) system can be considered as a “mini genome model” and can also be termed as “self-surveillance complex.” Recent research suggests that HLA allele–specific expression puts an additional layer of complexity and polymorphism beyond the genomic diversity. Although attempts are being made to reveal mechanistic insights of HLA association with various infectious and autoimmune diseases, the novel mechanisms defining this allele-specific expression variability and its importance in the context of disease development and/or immune aberrations are largely unknown. In the post-genomic era impressive technological advancements have been made toward identifying novel alleles thus paving the way for developing robust diagnostic and therapeutic approaches, particularly in the field of transplantation medicine. HLA matching, antibody detection, and involvement of other hitherto unexplored factors are relevant in long-term acceptance of the organ and hematopoietic stem cell graft. Designing individualized immunosuppressive regimens based on immunological stratification (HLA and non-HLA factors) will be helpful for evading chronic allograft loss in long term.