Human leucocyte antigen (HLA) genes

Play a major etiologic role in autoimmunity and infectious disease and they determine tissue compatibility.

Crucial genes that regulate immune function.

The human leukocyte antigen region is the most polymorphic region of the human genome.

HLA testing is used in both solid organ and hematopoietic stem cell transplantation, to support immune platelet refractory patients, and for pharmacogenomics testing.

Initially HLA typing was done through the use of antibodies via serological methods.

Presently HLA typing is done through molecular methods.

Each human cell expresses six MHC class I alleles-one HLA-A, -B, and -C allele from each parent) and six to eight MHC class II alleles-one HLA-DP and -DQ, and one or two HLA-DR from each parent, and combinations of these

HLA antigens are inherited on the short arm of chromosome six and separated into two clinically relevant classes: numeral I-HLA A,B,and C. and II HLA DRB1, DQB1, and DPB1.

Each HLA antigen is inherited as 2 haplotypes: one from the mother and one from the father.

Polymorphisms are HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DQ and HLA-DP.

HLA genes are highly polymorphic at multiple locations, however the majority of these DNA sequence variations are within exons 2 and 3.

The MHC variation is high, with at least 350 alleles for HLA-A genes, 620 alleles for HLA-B, 400 alleles for DR, and 90 alleles for DQ.

Increased precision of typing is available with polymerase chain reaction based techniques.

Matching by high resolution DNA typing methods can discover transplant determinants and therefore are required for the donors evaluation, the risk of graft rejection, GVHD, and mortality may be greater for those with serologic mismatches than with allele mismatches and the risk of GVHD and mortality increased with increasing numbers of HLA mismatches.

Major compatibility complex (MHC) is a 7-megabase region with dense clustering of more than 300 genes coordinating immune function.

MHC has an average gene density of 1/16 kb and more than 420 associations to more than 35 common complex autoimmune, inflammatory, infectious diseases and malignancy have been described.

The main HLA loci are the best characterized MHC genes.

The HLA matching decreases the risk of non-engraftment in hematopoietic cell transplants, decreases acute and chronic graft versus host disease and mortality.

HLA genes can influence drug responses.

HLA polymorphisms are associated with increased risk for specific diseases.

The presence of a HLA type and its association with a specific disease is not, however, sufficient to trigger disease, as demonstrated by HLA-B27.

In HLA-B27 is a common antigen but ankylosing spondylitis is an uncommon process.

HLA types have been associated with chronic lymphocytic leukemia, multiple myeloma, acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and Hodgkin’s disease.

Certain HLA types associated with solid organ malignancies have been identified, so that there is an increased risk of progression to hepatocellular carcinoma in patients with chronic hepatitis B.

HLA antibodies, associated with immune refractoriness to platelet transfusions.

HLA genes make proteins called human leukocyte antigens (HLA), which take bits and pieces of proteins from inside the cell and display them on the cell’s surface.

If the cell is cancerous or infected, the HLA proteins display abnormal fragments that trigger immune cells to destroy that cell and any others displaying the same fragment.

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