Diagnostic, prognostic and therapeutic aspects of systemic lupus erythematosus and rheumatoid arthritis.

Rheumatoid arthritis and systemic lupus erythematosus are rheumatic diseases characterized by excessive immunoreactivity. Exaggerated immunity is manifested as auto-antibody production and aberrant cell-mediated reactions directed against autologous tissue. Although the mechanisms and site for abnormal immune responses are not completely understood, risk factors that predispose an individual to develop rheumatoid arthritis or systemic lupus erythematosus can be defined. Genetic factors, especially HLA genes, play an important role in rendering a host susceptible to the sequelae of immunologically mediated diseases. Modern technology, such as T-cell cloning, can be used to dissect polymorphic HLA determinants involved in the genetic susceptibility for rheumatoid arthritis and systemic lupus erythematosus. Mapping of disease-associated determinants in rheumatoid arthritis patients suggests that polymorphic sites within the third hypervariable region of the HLA-DR beta 1-chain are functionally involved in the initiation and perpetuation of the disease. These HLA-determinants function to mediate the contact between the HLA- and the T-cell receptor molecules. In systemic lupus erythematosus patients, the role of disease associated molecules appears to be distinct; genetic susceptibility is correlated to patterns of auto-antibody productions. Immunogenetic studies may provide diagnostic tools to subset patients with rheumatoid arthritis and systemic lupus erythematosus and develop prognostic markers to tailor immunomodulatory therapy. Both diseases are characterized by high levels of morbidity and mortality, but can now be mitigated by the careful and judicious use of immunosuppressives.