Abstract
Epstein-Barr virus (EBV) has been found by many serology studies to be associated with systemic lupus erythematosus (SLE). However, the results of DNA studies have been conflicting. Therefore, instead of antibody to EBV, we studied the association between EBV DNA and SLE. In this case-control study in Taiwan, we enrolled 87 SLE patients and 174 age- and sex-matched controls. Peripheral blood mononuclear cells of SLE patients and matched controls were tested for EBV DNA by polymerase chain reaction (PCR) and Southern blot. Of the 87 SLE patients, 71 (81.6%) were found to be positive for EBV DNA, while 85 (48.9%) of the 174 controls (odds ratio 4.64, 95% confidence interval 2.50–8.62, P<0.0001) were positive. While the EBV DNA-positive rate did not decline with age in SLE patients (P>0.05), it did decline with age in controls (P<0.05). Furthermore, based on a real-time quantitative PCR study, we have found a significant difference between EBV viral load in SLE and controls (P=0.008). Therefore, in our molecular study of DNA level, we found evidence for the association of EBV infection and SLE, suggesting that EBV contributes, if not to the development of SLE, then to disease perpetuation.
Similar content being viewed by others
References
Arbuckle MA, Reichlin M, Harley JB, James JA (1999) The development of lupus humoral autoimmunity for anti-Sm autoantibodies is consistent with predictable sequential B cell epitope spreading. Scand J Immunol 50:447–455
Aya T, Mizuno F, Osato T (1980) Immunologic cytotoxicity against autologous human lymphocytes transformed or infected by Epstein-Bar virus: role of antibody-dependent cellular cytotoxicity in health individuals. J Natl Cancer Inst 65:265–271
Evans AS, Rothfield NF, Niederman JC (1971) Raised antibody titres to E.B. virus in systemic lupus erythematosus. Lancet I:167–168
Gergely L, Czegledy J, Vaczi L, Gonczol E, Szegedi G, Berenyi E (1973) EBV antibodies in systemic lupus erythematosus. Lancet I:325–326
Harley JB, Gaither, KK (1988) Autoantibodies. Rheum Dis Clin North Am 14:43–56
Harley JB, James JA (1995) Autoepitopes in lupus. J Lab Clin Med 126:509–516
Hochberg MC (1997) Updating the American College of Rheumatology 1997 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725
Incaprera M, Rindi L, Bazzichi A, Garzelli C (1998) Potential role of the Epstein-Barr virus in systemic lupus erythematosus autoimmunity. Clin Exp Rheumatol 16:289–294
James JA, Harley JB (1992) Linear epitope mapping of an Sm B/B’ polypeptide. J Immunol 148:2074–2079
James JA, Kaufman KM, Farris AD, Taylor-Albert E, Lehman TJ, Harley JB (1997) An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus. J Clin Invest 100:3019–3026
James JA, Scofield RH, Harley JB (1997) Lupus humoral autoimmunity after short peptide immunization. Ann N Y Acad Sci 815:124–127
James JA, Neas BR, Moser KL, Hall T, Bruner GR, Sestak AL, Harley JB (2001) Systemic lupus erythematosus in adults is associated with previous Epstein-Barr virus exposure. Arthritis Rheum 44:1122–1126
Kang I, Quan T, Nolasco H, Park SH, Hong MS, Crouch J, Pamer EG, Howe JG, Craft J (2004). Defective control of latent Epstein-Barr virus infection in systemic lupus erythematosus. J Immunol 172:1287–1294
Klippel JH, Decker JL (1973) Epstein-Barr virus antibody and lymphocyte tubuloreticular structures in systemic lupus erythematosus. Lancet II:1057–1058
Lau CS, Yuen KY, Chan KH, Wong RW (1998) Lack of evidence of active lytic replication of Epstein-Barr and cytomegaloviruses in patients with systemic lupus erythematosus. Chin Med J (Engl) 111:660–665
Llorente L, Zou W, Levy Y, Richaud-Patin Y, Wijdenes J, Alcocer-Varela J, et al (1995) Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. J Exp Med 181:839–844
Mahot S, Sergeant A, Drouet E, Grauffat H (2003) A novel function for the Epstein-Barr virus transcription EB1/Zta: induction of transcription of the hIL-10 gene. J Gen Virol 84:965–974
Marchini B, Dolcher MP, Sabbatini A, Klein G, Migliorini P (1994) Immune response to different sequences of the EBNA I molecule in Epstein-Barr virus-related disorders and in autoimmune diseases. J Autoimmun 7:179–191
Miyashita EM, Yang B, Lam KM, Crawford DH, Thorley-Lawson DA (1995) A novel form of Epstein-Barr virus latency in normal B cells in vivo. Cell 80:593–601
Newkirk, MM, Tsoukas C (1992) Effect of ultraviolet irradiation on selected host cell proteins including Ro/SS-A and Epstein-Barr virus in cultured lymphoblastoid cell lines. J Autoimmun 5:511–525
Phillips PE, Hirshaut Y (1973) Epstein-Barr virus antibody levels in systemic lupus erythematosus. Arthritis Rheum 16:97–101
Saito I, Servenius B, Compton T, Fox RI (1989) Detection of Epstein-Barr virus DNA by polymerase chain reaction in blood and tissue biopsies from patients with Sjogren’s syndrome. J Exp Med 169:2191–2198
Scofield RH, James JA (1999) Immunization as a model for systemic lupus erythematosus. Semin Arthritis Rheum 29:140–147
Tsai YT, Chiang BL, Kao YF, Hsieh KH (1995) Detection of Epstein-Barr virus and cytomegalovirus genome in white blood cells from patients with juvenile rheumatoid arthritis and childhood systemic lupus erythematosus. Int Arch Allergy Immunol 106:235–240
Tsokos GC, Magrath IT, Balow JE (1983) Epstein-Barr virus induces normal B cell responses but defective suppressor T cell responses in patients with systemic lupus erythematosus. J Immunol 131:1797–1801
Yokochi T, Yanagawa A, Kimura Y, Mizushima YJ (1989) High titer of antibody to the Epstein-Barr virus membrane antigen in sera from patients with rheumatoid arthritis and systemic lupus erythematosus. J Rheumatol 16:1029–1032
Acknowledgements
We are very grateful to our patients for donation of blood samples. The technical assistance of Miss Pei-Pei Chen, Miss Ming-Chi Yang and Mr. Hang-Ming Chang is highly appreciated. We thank Mr. Steed for editorial assistance with this manuscript. This study was supported by the Yu-Zu memorial prize for lupus research, Kaohsiung Medical University (grant no. KMU 92-A-03), and Chang Gung Memorial Hospital (grant no. BMRP 743). We are grateful for the encouragement and guidance from Prof. Kuei-Hsiang Lin and Prof. Hong-Wen Liu at Kaohsiung Medical University.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yu, SF., Wu, HC., Tsai, WC. et al. Detecting Epstein-Barr virus DNA from peripheral blood mononuclear cells in adult patients with systemic lupus erythematosus in Taiwan. Med Microbiol Immunol 194, 115–120 (2005). https://doi.org/10.1007/s00430-004-0230-5
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00430-004-0230-5