| Research Abstract |
We have previously found direct evidence that Epstein-Barr virus (EBV) exists in the cells of the synovial lining in patients with rheumatoid arthritis (RA) (International Immunology 9, 719-743, 1997). However, the mechanisms for this virus in the synovial cells of RA patients remain unknown. In a recent study searching for the causative gene of X-linked lymphoprolipherative disease, the gene directly linked to EBV-specific cytotoxic T cells was discovered, and its product is now referred to as signaling lymphocytic-activation molecule associated protein (SAP). In the present study, we attempted to investigate the involvement of SAP gene in RA.Using a quantitative real-time polymerase chain reaction (PCR), the expression level of SAP transcripts in peripheral leukocytes or T cells was examined for patients with RA, systemic lupus erythematosus (SLE), palindromic RA, or chronic renal diseases, as well as normal individuals. Nucleotide sequence of SAP cDNAs obtained from peripheral leukocytes of RA patients was determined to examine any mutations. The expression level of SAP transcripts in peripheral leukocytes of 21 RA patients was significantly lower than that of 13 normal individuals (p=0.0007), 4 patients with palindromic RA, 11 with inactive SLE, or 17 with chronic renal diseases. The decreased expression of SAP transcripts in RA patients was also observed in peripheral CD2+ T cells compared with normal individuals. There was no mutation in the coding region of SAP cDNAs derived from peripheral leukocytes of 5 RA patients. The decreased expression of SAP transcripts in peripheral leukocytes or T cells of RA patients might lead to the failure of the immune system to eliminate the EBV-infected synovial lining cells in joints of RA patients. Our findings have suggested that decreased expression of SAP gene might be involved in the onset or progress of RA.
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