Department of Internal Medicine, Toho University Graduate School of Medicine, Tokyo, Japan.
Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
PLoS One. 2018 Dec 11;13(12):e0208957. doi: 10.1371/journal.pone.0208957. eCollection 2018.
The objective of the present study was to investigate Epstein-Barr virus (EBV) infection as an environmental factor for the development of rheumatoid arthritis (RA).
Synovial tissues were collected during surgery from 128 RA and 98 osteoarthritis (OA) patients. DNA was extracted from synovial tissues. The EBV gene was assessed by nested PCR for the amplification of EBV nuclear antigen-1 (EBNA-1). The nucleotide sequence of the PCR product was elucidated. HLA-DRB1 genotyping was also performed.
EBV DNA was more frequently detected in the synovial tissues of RA patients (32.8%) than OA patients (15.3%) (p<0.01). The frequency of EBNA-1 variants did not significantly differ between RA and OA (RA: 17%, OA: 13%). The population with the HLA-DRB1 shared epitope (SE) was significantly higher in RA patients (70.3%) than in OA patients (44.9%) (p<0.001). In RA patients, the presence of EBV DNA was similar among SE-positive and -negative patients (SE-positive: 34.4%, -negative: 28.9%). The population with the EBNA-1 variant did not significantly differ between SE-positive and -negative patients (SE-positive: 12.9%, -negative: 27.3%).
The present results indicate that EBV infection contributes to the onset of RA and chronic inflammation in synovial tissues. The frequency of EBNA-1 gene variants was low and not significantly different between RA and OA, suggesting that EBNA-1 gene variants are not a risk factor for RA. HLA-DRB1 with SE is a genetic risk factor for the development of RA. However, neither the presence of EBV nor EBNA-1 gene variants differed between SE-positive and -negative RA patients. Therefore, these two risk factors, SE and EBV, may be independent.
EBV infection may be an environmental risk factor for the development of RA, while nucleotide variants of EBNA-1 do not appear to contribute to its development.
本研究旨在探讨 Epstein-Barr 病毒（EBV）感染作为类风湿关节炎（RA）发病的环境因素。
收集 128 例 RA 和 98 例骨关节炎（OA）患者手术时的滑膜组织。从滑膜组织中提取 DNA。通过巢式 PCR 扩增 EBV 核抗原-1（EBNA-1）评估 EBV 基因。阐明 PCR 产物的核苷酸序列。还进行了 HLA-DRB1 基因分型。
RA 患者滑膜组织中 EBV DNA 的检出率（32.8%）明显高于 OA 患者（15.3%）（p<0.01）。RA 和 OA 之间的 EBNA-1 变体频率无显著差异（RA：17%，OA：13%）。HLA-DRB1 共享表位（SE）人群在 RA 患者中（70.3%）明显高于 OA 患者（44.9%）（p<0.001）。在 RA 患者中，EBV DNA 的存在在 SE 阳性和阴性患者之间相似（SE 阳性：34.4%，阴性：28.9%）。SE 阳性和阴性患者之间的 EBNA-1 变体人群无显著差异（SE 阳性：12.9%，阴性：27.3%）。
本研究结果表明，EBV 感染导致 RA 发病和滑膜组织慢性炎症。EBNA-1 基因变异的频率较低，RA 和 OA 之间无显著差异，提示 EBNA-1 基因变异不是 RA 的危险因素。具有 SE 的 HLA-DRB1 是 RA 发病的遗传危险因素。然而，SE 阳性和阴性 RA 患者之间的 EBV 存在和 EBNA-1 基因变异无差异。因此，这两个危险因素 SE 和 EBV 可能是独立的。
EBV 感染可能是 RA 发病的环境危险因素，而 EBNA-1 核苷酸变异似乎对其发病无贡献。
