Impact of HLA-DQ Mismatch on Acute Rejection of Kidney Transplantation

Introduction Human Leukocyte Antigens (HLA). The major histocompatibility complex (MHC) is a gene region coding for cell surface proteins important for the immune system. MHC is the most complex immunogenetic system presently known in humans . HLA are groups of cell surface proteins encoded by genes in MHC which are known as HLA in humans and H-2 in mice .

HLA genes are located on the short arm of chromosome 6 at 6p21 position , occupying a genetic region of 4Mbps. The human immune system uses HLA's uniqueness to distinguish self from non-self. HLA are responsible for the presentation of "foreign" peptides (antigens) to the immune competent cells. T lymphocytes recognize foreign antigens only when it combines with HLA molecules.

Humans have three class I HLA (A, B, C) that are present on all nucleated cells and six class II HLA (DPA1, DPB1, DQA1, DQB1, DRA, DRB1) that are present only on antigen-presenting cells and lymphocytes. Three of the seven heterodimers (HLA-A, -B, and -DRB1) contribute to the majority of immunogenicity of mismatched antigens and therefore traditional HLA-typing methods have primarily focused on these alleles .

Renal transplantation is the gold standard therapeutic strategy of replacing renal dysfunctions that offers the best survival to the patients with end-stage renal disease (ESRD). Kidney transplantation is associated with 68% lower risk of death than dialysis . Graft and patient survival after kidney transplantation have improved over the past decade. Death-censored graft survival has increased steadily over the past decade in both adults and pediatric recipients. Data provided by the Scientific Registry of Transplant Recipients (SRTR) demonstrate a 10-year overall graft survival for both living and deceased donors of approximately 55 to 60 percent compared with 35 to 40 percent from a decade prior .

Renal transplantation success is dependent on the reaction of the immune system primarily against human leucocyte antigen (HLA) proteins of the transplant. Patients previously exposed to non-self HLA through transplant, blood transfusions or pregnancy may develop antibodies reactive to HLA .