| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
|---|
| Research Abstract |
We have investigated the pathogenic relationship between systemic lupus erythematosus (SLE) and human endogenous retrovirus (HERV). our results indicated that transcription and translation of HERV clone 4-1 were increased in SLE patients, but not normal individuals. HERV clone 4-1 antigens in lymphocytes and their serum antibodies were detected in SLE patients. DNA hypomethylation and inactivation of stop codons in clone 4-1 of SLE seem to contribute to the development of these transcription and translation of clone 4-1. Our computer search of current entries in sequence libraries (GenBank database) indicated >90% sequence homology of genomic DNA from the SLE clone 4-1 gag region and the consensus sequence of clone 4-1 located on chromosome 11 of normal individuals, including inactivation of these stop codons, unlike clone 4-1 on the other chromosomes, thus, our findings raised the possibility that the clone 4-1 transcribed in SLE patients may be derived from chromosome 11. Our recent studies have also indicated that clone 4-1-derived synthetic peptides can induce the T cell abnormalities and polyclonal B cell activation in vitro observed in SLE.HERV have repeatedly been suggested as etiologic factors in autoimmune rheumatic diseases, including SLE, but despite intensive research the role of HERV in these diseases remains unclear and unproven. Our results may contribute to the elucidation of these issues.
The creation of the transgenic mice or immunization of mice with DNA from SLE clone 4-1 may be useful for elucidation of the autoimmune mechanism of SLE, and we are planning to perform such experiments.
|
