HL-A antigens in clinical medicine

Many autoimmune diseases show a significant association with one or two second segregant series histocompatibility antigens. These associations are of great scientific interest, since they support the concept of HL-A-linked immune-response genes governing specific disease susceptibility. However, with one major exception, the association of HL-A antigens with diseases is not striking enough to provide a worthwhile diagnostic test. The exception is the extraordinarily high incidence of HLA B27 in patients with seronegative spondyloarthropathy best typified by ankylosing spondylitis (AS) and Reiter's disease (RD). In patients with these rheumatic syndromes, the antigen is present in more than 90% of cases compared to an incidence of approximately 6% in normal Caucasians and 4% in black Afro-Americans. The vast majority of rheumatic diseases are readily diagnosable on the basis of a history, physical examination and careful radiographic survey. This applies to most patients with a seronegative spondyloarthropathy, especially when the disease presents as a typical and fully formed clinical syndrome characterized as AS or RD. Sometimes the initial clinical nature may be atypical and only long-term follow-up of the patient will reveal an evolution toward the typical syndrome. In these situations, the correct diagnosis is reinforced by detecting the presence of HLA B27 on the patient's cells. Examination of the patient's family often reveals a high incidence of similar clinical syndromes, nearly always associated with the presence of the antigen. Since tissue typing at the moment is an expensive and relatively unavailable laboratory technic, its widespread and indiscriminatory use as a diagnostic test cannot be encouraged. However, in the clinical settings outlined above, tissue typing provides an invaluable diagnostic test. Presently, the combination of a negative test for rheumatoid factor and a positive test for HLA B27 is one of the strongest diagnostic laboratory profiles available to the physician when faced with a patient with early or atypical rheumatic disease. Aside from the purely clinical setting, the most exciting aspect of the association between these diseases and a specific cell surface antigen lies in the hope that we have a clue to the pathogenesis of a group of common rheumatic disorders. If the cause or causes of spondyloarthropathy can one day be found, the detection of HLA B27 may provide a useful public health measure facilitating preventive medicine. Even now, the detection of susceptible subjects within a family or a population will open the way for early diagnosis and treatment.