Detection of Epstein-Barr virus in synovial fluid of rheumatoid arthritis patients

Authors

  • Ramezan Ali Ataee Ph.D. of Medical Microbiology, Professor, Department of Virology and Bacteriology, and Clinical Development Medical Center of Baqiyatallah Hospital, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran

Keywords:

rheumatoid arthritis, EBV, EBNA-1, PCR

Abstract

Introduction: Rheumatoid arthritis (RA) is one of the most common chronic inflammatory disorders. Genes and environmental factors contribute to RA. Epstein–Barr Virus (EBV) has been considered as one the RA pathogeneses. The aim of this study was to detect of the EBV genome in patients with RA. 

Methods: In this cross-sectional study, 50 samples of synovial fluid were obtained from patients with RA from 2010–2012. Using a standard of the EBV genome and EBNA-1-specific primers, the method of PCR was set up. Then, all of the samples of synovial fluids separately were subjected to DNA extraction and Polymerase Chain Reaction (PCR) amplification. Data were analyzed using SPSS version 18.0. The statistical analysis was performed by the t-test.

Results: The demographic and laboratory characteristic assay revealed that the mean age of patients was 49, and the patients were 60% males and 40% females. In addition, in all cases, the mean rheumatoid factor (RF) levels of the patients were below the normal level. The results of this study showed that the PCR was able to detect EBV DNA in > 60% of the cases.

Conclusion: The results of this study indicated that EBV was frequently detected in the synovial fluid of RA patients. Thus, EBV may be a strong candidate that can act at several levels of the pathophysiology of RA. However, these findings also indicated that EBV may play a role in the pathogenesis of RA. However, the possible relationship between RA and EBV must be determined by further research.

References

Epstein MA, Barr YM, Achong BG. Virus particles in cultured lymphoblasts from Burkitt’s lymphoma.

Lancet. 1964; 1(7335): 702–3. doi: 10.1016/S0140-6736(64)91524-7, PMID: 14107961.

Young LS, Rickinson AB. Epstein-Barr virus: 40 years on. Nat Rev Cancer. 2004; 4(10): 757–68. PMID:

Alspaugh MA, Jensen FC, Rabin H, Tan EM. Lymphocytes transformed by Epstein-Barr virus: induction

of nuclear antigen reactive with antibody in rheumatoid arthritis. J Exp Med. 1978; 147(4): 1018–27.

PMID: 206643.

Baboonian C, Halliday D, Venables PJ, Pawlowski T, Millman G, Maini RN. Antibodies in rheumatoid

arthritis react specifically with the glycine alanine repeat sequence of Epstein-Barr virus nuclear antigen-1.

Rheumatol Int. 1989; 9: 161–6. PMID: 2481875.

Kosaka S. Detection of antibody to a new antigen induced by Epstein-Barr virus in rheumatoid arthritis.

Tohoku J Exp Med. 1979; 127: 157–60. PMID: 216133.

Catalano MA, Carson DA, Slovin SF, Richman DD, Vaughan JH. Antibodies to Epstein-Barr virus- determined antigens in normal subjects and in patients with seropositive rheumatoid arthritis. Proc Natl

Acad Sci U S A. 1979; 76: 5825–8. PMID: 230491.

Alspaugh MA, Henle G, Lennette ET, Henle W. Elevated levels of antibodies to Epstein-Barr virus

antigens in sera and synovial fluids of patients with rheumatoid arthritis. J Clin Invest. 1981; 67: 1134–40.

PMID: 6259211.

Ferrell PB, Aitcheson CT, Pearson GR, Tan EM. Seroepidemiological study of relationships between

Epstein-Barr virus and rheumatoid arthritis. J Clin Invest. 1981; 67: 681–7. PMID: 6259207.

Sculley TB, Walker PJ, Moss DJ, Pope JH. Identification of multiple Epstein-Barr virus-induced nuclear

antigens with sera from patients with rheumatoid arthritis. J Virol. 1984; 52: 88–93. PMID: 6090712.

Hazelton RA, Sculley TB, Pope JH. The prevalence of antibodies to an Epstein-Barr virus-induced

polypeptide (EBNA-2) in the sera of rheumatoid arthritis families. Br J Rheumatol. 1987; 26: 193–6.

PMID: 3034370.

Shimizu N, Yamaki M, Sakuma S, Ono Y, Takada K. Three Epstein-Barr virus (EBV)-determined nuclear

antigens induced by the BamHI E region of EBV DNA. Int J Cancer. 1988; 41: 744–51. PMID:2835324.

Fox R, Sportsman R, Rhodes G, Luka J, Pearson G, Vaughan J. Rheumatoid arthritis synovial membrane

contains a 62,000-molecular-weight protein that shares an antigenic epitope with the Epstein-Barr virus- encoded associated nuclear antigen. J Clin Invest. 1986; 77: 1539–47. PMID: 2422209.

Alspaugh MA, Shoji H, Nonoyama M. A search for rheumatoid arthritis-associated nuclear antigen and

Epstein-Barr virus specific antigens or genomes in tissues and cells from patients with rheumatoid arthritis.

Arthritis Rheum. 1983; 26: 712–20. PMID: 6190485.

Fox RI, Chilton T, Rhodes G, Vaughan JH. Lack of reactivity of rheumatoid arthritis synovial membrane

DNA with cloned Epstein Barr virus DNA probes. J Immunol. 1986; 137: 498–501. PMID: 3013992.

Brousset P, Caulier M, Cantagrel A, Dromer C, Mazieres B, Delsol G. Absence of Epstein-Barr virus

carrying cells in synovial membranes and subcutaneous nodules of patients with rheumatoid arthritis. Ann

Rheum Dis. 1993; 52: 608–9. PMID: 8215625.

Zhang L, Nikkari S, Skurnik M, Ziegler T, Luukkainen R, Mo¨tto¨nen T, et al. Detection of herpesviruses

by polymerase chain reaction in lymphocytes from patients with rheumatoid arthritis. Arthritis Rheum.

; 36: 1080–6. doi: 10.1002/art.1780360808, PMID: 8343184.

Takei M, Mitamura K, Fujiwara S, Horie T, Ryu J, Osaka S, et al. Detection of Epstein-Barr virus-encoded

small RNA 1 and latent membrane protein 1 in synovial lining cells from rheumatoid arthritis patients. Int

Immunol. 1997; 9: 739–43. PMID: 9184919.

Mousavi Jazi M, Bostrom L, Lovmark C, Linde A, Brytting M, Sundqvist VA. Infrequent detection of

cytomegalovirus and Epstein-Barr virus DNA in synovial membrane of patients with rheumatoid arthritis. J

Rheumatol. 1998; 25: 623–8. PMID: 9558160.

Saal JG, Krimmel M, Steidle M, Gerneth F, Wagner S, Fritz P, et al. Synovial Epstein-Barr virus infection

increases the risk of rheumatoid arthritis in individuals with the shared HLA–DR4 epitope. Arthritis

Rheum. 1999; 42: 1485–96. PMID: 10403278.

Scotet E, David-Ameline J, Peyrat MA, Moreau-Aubry A, Pinczon D, Lim A, et al. T cell response to

Epstein-Barr virus transactivators in chronic rheumatoid arthritis. J Exp Med. 1996; 184: 1791–800. PMID:

, PMCID: PMC2192863.

Koide J, Takada K, Sugiura M, Sekine H, Ito T, Saito K, et al. Spontaneous establishment of an Epstein- Barr virus-infected fibroblast line from the synovial tissue of a rheumatoid arthritis patient. J Virol. 1997;

: 2478–81. PMID: 9032386.

Alspaugh MA, Shoji H, Nonoyama M. A search for rheumatoid arthritis-associated nuclear antigen and

Epstein-Barr virus specific antigens or genomes in tissues and cells from patients with rheumatoid arthritis.

Arthritis Rheum. 1983; 26: 712–20. PMID: 6190485.

Wang W, Chien YC, Jan JS, Chueh CM, Lin JC. Consistent Sequence Variation of Epstein-Barr Virus

Nuclear Antigen 1 in Primary Tumor and Peripheral Blood Cells of Patients with Nasopharyngeal

Carcinoma. Clin Cancer Res. 2002; 8: 2586-90. PMID: 12171888.

Sewell KL, Trentham DE. Pathogenesis of rheumatoid arthritis. Lancet. 1993; 1: 283–6. PMID: 8093927.

Takeda T, Mizugaki Y, Matsubara L, Imai S, Koike T, Takada K. Lytic Epstein-Barr virus infection in the

synovial tissue of patients with rheumatoid arthritis. Arthritis Rheum. 2000; 43: 1218–25. doi:

1002/1529-0131(200006)43:6<1218::AID-ANR4>3.0.CO;2-2, PMID: 10857780.

Saal JG, Krimmel M, Steidle M, Gerneth F, Wagner S, Fritz P, et al. Synovial Epstein-Barr virus infection

increases the risk of rheumatoid arthritis in individuals with the shared HLA-DR4 epitope. Arthritis

Rheum. 1999; 42: 1485–96. doi: 10.1002/1529-0131(199907)42:7<1485::AID-ANR24>3.0.CO;2-7,

PMID: 10403278.

Chiu WC , Chen CM , Cheng TT, Huey-Ling You HL, Yu SF, Weng LH, et al. EBV-encoded small RNA1

and nonresolving inflammation in rheumatoid arthritis. Kaohsiung J of Med Sci. 2013; 29: 606-10. doi:

1016/j.kjms.2013.04.002, PMID: 24183354.

Balandraud N, Roudier J, Roudier C. Epstein–Barr virus and rheumatoid arthritis. Autoimmunity Reviews.

; 3: 362– 7. doi: 10.1016/j.autrev.2004.02.002, PMID: 15288002.

Balandraud N, Meynard JB, Auger I, Sovran H, Mugnier B, Reviron D, et al. Epstein-Barr Virus Load in

the Peripheral Blood of Patients With Rheumatoid Arthritis. Arthritis Rheum. 2003; 48: 1223–8. doi:

1002/art.10933, PMID: 12746895.

Ataee RA, Karami A, Izadi M, Aghania A, Ataee MH. Molecular screening of staphylococcal enterotoxin

B gene in clinical isolates. Cell J. 2011; 13: 187-92. PMID: 23508641. PMCID: PMC3584468.

Ataee RA, Ataee MH, Alishiri GH, Esmaeili D. Staphylococcal enterotoxin C in synovial fluid of patients

with rheumatoid arthritis. Iran Red Crescent Med J. 2014; 16: e16075. doi: 10.5812/ircmj.16075.

Zahiri YS, Ataee RA, Alishiri GH, Movahedi M. Bacteriological and molecular assessment of

staphylococcal enterotoxin e in the blood of patients with rheumatoid arthritis. Jundishapur J Microbiol.

; 8: e16621. doi: 10.5812/jjm.16621.

Golmohammadi R, Ataee RA, Alishiri GH, Mirnejad R, Mehrabi TA, Esmaieli D. Design of PCR-based

method for detection of a gene-encoding Mycoplasma arthritidis mitogen superantigen in synovial fluid of

rheumatoid arthritis patients. Iran J Microbiol. 2014; 6: 415-20. PMID: 25926960. PMCID: PMC4411428.

Ataee RA, Golmohammadi R, Alishiri GH, Mirnejad R, Najafi A, Esmaeili D et al. Simultaneous Detection

of Mycoplasma pneumoniae, Mycoplasma hominis and Mycoplasma arthritidis in Synovial Fluid of

Patients with Rheumatoid Arthritis by Multiplex PCR. Arch Iran Med. 2015; 18: 345-50. doi:

/AIM.004.

Ataee RA, Mehrabi-Tavana A, Izadi M, Hosseini SM, Ataee MH. Bacterial meningitis: a new risk factor. J

Res Med Sci. 2011; 16: 207-10. PMID: 22091233, PMCID: PMC3214305.

Published

2022-03-07

Issue

Section

Articles