Journal Article

Epstein-Barr virus infection and variants of Epstein-Barr nuclear antigen-1 in synovial　tissues of rheumatoid arthritis

Masuoka, Shotaro, Takahashi, Hiroshi, Tsuchiya, Kazuaki, Nanki, Toshihiro, Kusunoki, Natsuko, Takamatsu, Ryo, Kawai, Shinichi

2018

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Antigens / Arthritis / Arthritis, Rheumatoid - genetics / Arthritis, Rheumatoid - pathology / Arthritis, Rheumatoid - virology / Autoimmune diseases / Biocompatibility / Biology and Life Sciences / Biomedical materials / Bone surgery / Chronic infection / Cytomegalovirus / Deoxyribonucleic acid / DNA / DNA polymerase / Drb1 protein / EBNA-1 protein / Ecological risk assessment / Environmental factors / Environmental risk / Epitopes / Epitopes - genetics / Epitopes - immunology / Epstein-Barr virus / Epstein-Barr Virus Infections - genetics / Epstein-Barr Virus Infections - physiopathology / Epstein-Barr Virus Infections - virology / Epstein-Barr Virus Nuclear Antigens - genetics / Epstein-Barr Virus Nuclear Antigens - immunology / Epstein-Barr Virus Nuclear Antigens - isolation & purification / Female / Genotyping / Herpesvirus 4, Human - genetics / Herpesvirus 4, Human - isolation & purification / Herpesvirus 4, Human - pathogenicity / Histocompatibility antigen HLA / HLA-DRB1 Chains - genetics / HLA-DRB1 Chains - immunology / Humans / Immune system / Infections / Inflammation / Internal medicine / Lymphoma / Male / Medicine / Medicine and Health Sciences / Nucleotide sequence / Orthopedics / Osteoarthritis / Osteoarthritis - genetics / Osteoarthritis - physiopathology / Osteoarthritis - virology / Patients / Polymerase chain reaction / Proteins / Research and Analysis Methods / Rheumatoid arthritis / Rheumatology / Risk analysis / Risk Factors / Surgery / Synovial Fluid - virology / Tissues / Tumor necrosis factor-TNF / Viruses