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Kaposi's sarcoma-associated herpesvirus (KSHV): a new viral pathogen associated with Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease.

and may make an individual susceptible or resistant to a particular disease. Also, the MHC region is densely packed with genes, many of which are important for function. Hence, mutations in this region of the genome are more likely to result in a disease than mutations in a region of the genome that has very few coding regions. Furthermore, the MHC region may be a "hot spot" for mutagenesis. Finally, the polymorphic nature of this region means that a mutation in or near the MHC complex is likely associated with a specific HLA type that is not found in many people. Hence, specific HLA types can serve as markers that are linked with defective genes in this region. While diseases have been known to be correlated with specific HLA loci for some years, recent advances in molecular biology have resulted in the discovery of many more disease associations. Classic serologic techniques define an HLA type by reactivity of an antibody or antisera with HLA molecules. DNA analysis has shown that one classic HLA type can be further subdivided into a set of alleles with slightly different sequences. These alleles are known as subtypes of an HLA type. If a disease is associated with only one particular HLA subtype, then studies employing classic serologic techniques might fail to establish a statistically significant correlation between the disease and HLA markers. In these cases, molecular techniques can determine HLA subtypes and might establish that one HLA subtype is associated with the disease. HLA studies can help investigators classify diseases. Juvenile rheumatoid arthritis (JRA), for example, can have several presentations. Researchers proposed classifying JRA into various subtypes based on clinical features and then found that different JRA subtypes correspond with different HLA subtypes. This provides evidence that different forms of JRA arise from different pathophysiologic mechanisms and may be responsive to different therapeutic interventions. Diseases that are associated with specific HLA types or subtypes include ankylosing spondylitis, type 1 diabetes mellitus, Behcet's disease, celiac disease, Grave's disease, Hashimoto's thyroiditis, Hodgkin's disease, idiopathic membranous nephropathy, idiopathic nephrotic syndrome, multiple sclerosis, narcolepsy, C2 deficiency, C4 deficiency, congenital adrenal hyperplasia, idiopathic hemochromatosis, gluten-sensitive enteropathy, pemphigus vulgaris, cicatrical pemphigoid, Goodpasture's syndrome, juvenile rheumatoid arthritis, and rheumatoid arthritis. In addition, susceptibility to malaria infection and rapid or slow progression of HIV infection are associated with specific HLA types. For most diseases, molecular techniques that determine HLA subtypes provide the most useful information. These studies can be complicated, however, because in some diseases, such as type 1 diabetes, certain HLA subtypes (DQA1 *0301, for example) are associated with an increased risk of contracting the disease but other subtypes (DQA1 *0 102, for example) are associated with a decreased risk of contracting the disease. Some of the diseases with the strongest associations with specific HLA genotypes in the general population are ankylosing spondylitis, narcolepsy, and celiac disease. HLA typing can be useful in many other diseases, however. Often when a family member has a disease, the family and physician want to know the likelihood that other family members will develop the disease. In these cases, comparing the HLA type of the proband with relatives can provide useful information even if the disease does not have a strong correlation with particular HLA subtypes in the general population. Also, in specific clinical situations, HLA testing may help refine a differential diagnosis or predict the progression of an illness.