Immunogenetics & Transplantation

Associations Between HLA Antigens & Specific Diseases

In humans, very striking associations are observed between particular HLA antigens and specific diseases. Some of these are listed in Table 19-3. In some diseases, the HLA molecule may be implicated in the pathogenesis. In others, the specific HLA allele may be linked to a gene determining immune responsiveness to a particular antigen.

The standard method for detecting HLA-A, -B, and -C antigens is that of lymphocyte microcytotoxicity. Lymphocytes isolated from peripheral blood or lymph nodes are added to each well of a typing tray filled with sera containing the appropriate cytotoxic alloantibody. When complement is added, cells to which antibody has been specifically bound will have complement activated at the cell surface, resulting in cell death or lysis. It is thus possible to type for all of the known HLA-A, -B, and -C specificities. An appreciable majority of typing serum samples are obtained from multiparous women since they form antibodies to fetal alloantigens.

Typing for the class II antigens HLA-DR and -DQ by serologic methods is technically more difficult. Antigens of the HLA-D, -DR, -DQ, and -DP series may also be detected by in vitro mixed lymphocyte culture (MLC). Lymphocytes of one individual (responder cells) will undergo proliferation upon encountering lymphocytes from another individual possessing foreign HLA-DR and -DQ antigens (stimulator cells). Lymphocyte proliferation can be readily measured by DNA incorporation of tritiated thymidine. Responders possessing matching -DR and -DQ antigens will remain nonreactive.

Increasingly, HLA class II typing is being performed by molecular technology. The DNA sequences for the HLA genes and their flanking sequences are known. Selected primers that amplify the gene of interest using the polymerase chain reaction (PCR) technique are known as sequence-specific primers. HLA typing by PCR provides better resolution than serologic identification because typing is done at the genetic level.

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_{Gonzalez S et al: Immunogenetics, HLA-B27 and spondyloarthropathies. Curr Opin Rheumatol 1999;11:257.}

McCurdy D: Genetic susceptibility to the connective tissue diseases. Curr Opin Rheumatol 1999;11:399.