Retroviral involvement in autoimmune disease: Serological and genetic evidence
Description
The potential role for retroviruses in systemic autoimmune disease increased following the isolation of Human intracisternal A-type retroviral particles (HIAP) froom cells co-cultured with autoimmune patient tissue. At the serological level, using western blots and other immunoassays, we have examined the relationship between apparent immune reactions to HIAP-I (or a similar retrovirus) and autoimmune disease. In Graves' disease we have demonstrated the presence of antibodies to a set of HIAP-I antigens, suggesting that a similar to HIAP may have a role in Graves' disease pathogenesis. In systemic lupus erythematosus, a role for HIAP is strengthened by a series of very significant serological correlations between known autoantigens and HIAP-I. Our study of Sjogren's syndrome (SS) serology confirms the presence of anti-retroviral antibodies in SS patients, the correlation of antibodies to the known SS autoantigens (SS-A, SS-B), and demonstrated the presence of other anti-retroviral antibodies in SS. Also noted in this study was an antigenic similarity between HIAP-I and human T lymphotrophic viruses (HTLV-I/II) was noted in a comparison of diabetic serum reactivity to the proteins of these two retroviruses In an examination of potential animal models of retroviral involvement in autoimmune disease (Graves' disease), we have shown a correlation between feline hyperthyroidism and seroreactivity to HIAP-I. Canine hypothyroidism demonstrated no similar correlation. An ancillary study of leukemia virus infected animals demonstrated that HIAP-I and FeLV may share some level of antigenic similarity In characterizing HIAP-I, this study demonstrates that: (1) HIAP-I producing cultures (MSC) show greater antigenic similarity to HIV-1 than either HIAP-II producing cells or the parent strain; (2) three specific proteins of HIAP-I were sized by western blot, with the identification of a cross-reactive HIV epitope; (3) the absence of proviral plasmid DNA in the MSC cells suggests that HIAP-I is a replication compromised retrovirus Finally, a genetic examination of HIAP-I may have identified a sequence related to HIAP-I's transformation of MSC cells. Through the use of low stringency hybridization and PCR we have also shown that the genome of HIAP-I is more divergent from that of HTLV-I and HIV-1 than other means of analysis may suggest