Development of molecular diagnostic assays for systemic autoimmune diseases

DESCRIPTION (provided by applicant): We aim to produce a significantly improved diagnostic system for autoimmune, rheumatologic disease. Similarities between autoimmune diseases and HIV-induced diseases led us to look for a retrovirus involved in autoimmune disease. We found a retrovirus, human intracisternal A-type particle (HIAP), in Sjogren's syndrome patients. Subsequently we found evidence indicating that HIAP is also involved in the development of juvenile rheumatoid arthritis, systemic lupus erythematosus, and Grave's disease. The consequences of these diseases to individual patients range from debilitating and disfiguring to fatal. The economic public health consequences are very high. The diagnostics currently available are not very specific so the development of new more specific diagnostic assays can lead to decrease mortality, earlier therapeutic intervention and reduced healthcare costs. In the first phase of this project we aim to clone the retrovirus by either cDNA library expression cloning or by mRNA differential display. When we believe we have cloned retroviral HIAP cDNA we will confirm that it is sequence from the retrovirus associated with Sjogren's syndrome by comparing the cloned cDNA to DMA and mRNA from HIAP-infected cells and from Sjogren's syndrome patients using PCR-based techniques. The viral DMA and mRNA should be present in infected cells and Sjogren's tissue, but not in normal, uninfected cells. After confirmation, we will clone the entire HIAP genome from cultured cells infected with the HIAP and from patient tissue samples. In the longer term, the cloned viral DMA will be used to produce recombinant proteins for use in new diagnostic assays. These HIAP-based assays will replace assays that are very sensitive for some autoimmune diseases, but not very specific in discriminating between the members of a cluster of autoimmune rheumatoid diseases that we have associated with the retrovirus. Our expectation is that each disease will be associated with a particular pattern of recombinant viral proteins because each disease has a unique set of serum antibodies that react with the viral proteins. We have evidence that Sjogren's syndrome and SLE patients have characteristic reactivity to isolated peptides from at least one retroviral protein. The development of better clinical diagnostics for autoimmune diseases will hasten diagnosis of diseases, especially the discrimination between diseases. This will, in turn, hasten proper treatment of patients preserving their health and prolonging life. In addition, the strengthened association of a retrovirus to these diseases will stimulate activity in new therapies for the diseases based on existing treatments for known retrovirus-caused disease.