ISOLATION AND CONTROL OF EPSTEIN-BARR VIRUS WHITCH DETECTED IN SYNOVIAL LINING IN PATIENTS WITH RHEUMATOID ARTHRITIS

我们先前已经发现直接证据表明，在类风湿性关节炎(RA)患者的滑膜衬里细胞中存在EB病毒(EBV)(国际免疫学9,719-743,1997)。然而，这种病毒在RA患者滑膜细胞中的作用机制尚不清楚。在最近一项寻找X连锁淋巴增殖性疾病致病基因的研究中，发现了与EBV特异性细胞毒性T细胞直接连锁的基因，其产物现在被称为信号淋巴激活分子相关蛋白(SAP)。在本研究中，我们试图探讨SAP基因在RA中的作用。采用实时定量聚合酶链式反应(PCR)检测RA、系统性红斑狼疮(SLE)、复发性RA、慢性肾脏疾病患者和正常人外周血白细胞或T细胞中SAP转录物的表达水平。测定RA患者外周血白细胞SAP cDNAs的核苷酸序列，以检测突变情况。21例RA患者外周血白细胞SAP转录水平显著低于13例正常人(P=0.0007)、4例复发性RA患者、11例稳定期SLE患者和17例慢性肾脏疾病患者。与正常人相比，RA患者外周血CD2+T细胞中SAP转录本的表达也降低。5例RA患者外周血白细胞SAP基因编码区未见突变。RA患者外周血白细胞或T细胞SAP转录本表达降低，可能导致免疫系统不能清除关节滑膜衬里细胞中EBV感染。提示SAP基因表达降低可能与RA的发生、发展有关。

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.