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. 1981 Apr;67(4):1134–1140. doi: 10.1172/JCI110127

Elevated Levels of Antibodies to Epstein-Barr Virus Antigens in Sera and Synovial Fluids of Patients with Rheumatoid Arthritis

Margaret A Alspaugh 1,2, Gertrude Henle 1,2, Evelyne T Lennette 1,2, Werner Henle 1,2
PMCID: PMC370674  PMID: 6259211

Abstract

The frequencies and levels of antibodies to Epstein-Barr virus (EBV)-specific antigens were determined in paired sera and synovial fluids from patients with rheumatoid arthritis (RA) and in sera from patients with other connective tissue diseases; i.e., systemic lupus erythematosus, progressive systemic sclerosis, and osteoarthritis (OA). The specimens were also tested for the presence of antibodies to RA-associated nuclear antigen. Compared to healthy controls, the patients' sera showed increased frequencies of elevated antibody titers (≥320) to Epstein-Barr viral capsid antigen, a correspondingly enhanced (twofold to threefold) geometric mean titer, and an increased frequency of antibodies at elevated titers (≥10), usually to the restricted component and rarely the diffuse component of the early antigen complex. Levels of antibody to the EBV-associated nuclear antigen were within the normal range. Enhancement of antibody titers was more pronounced in seropositive RA patients (i.e., positive for rheumatoid factor) than in those who were not. Enhancement was also found in systemic lupus erythematosus and progressive systemic sclerosis. Antibody to RA-associated nuclear antigen was detected at an increased frequency only in the group of seropositive RA patients (90%), as compared to 8-15% in the other connective tissue diseases and 6-8% in healthy controls. The antibody titers in the synovial fluids equaled or were at most twofold higher or lower than those in the sera. In addition, levels of EBV-specific antibodies were studied serially over a period of 6-10 mo in patients with RA and OA. Parameters of disease activity were determined and compared to antibody levels. EBV-specific antibodies in sera of OA patients remained constant and within normal limits throughout the study. Although EBV-specific antibodies were often elevated in RA patients, they also remained constant, with the exception of three patients, who showed gradual increases in one of the four antibodies, which did not correlate with disease activity.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alspaugh M. A., Jensen F. C., Rabin H., Tan E. M. Lymphocytes transformed by Epstein-Barr virus. Induction of nuclear antigen reactive with antibody in rheumatoid arthritis. J Exp Med. 1978 Apr 1;147(4):1018–1027. doi: 10.1084/jem.147.4.1018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alspaugh M. A., Talal N., Tan E. M. Differentiation and characterization of autoantibodies and their antigens in Sjögren's syndrome. Arthritis Rheum. 1976 Mar-Apr;19(2):216–222. doi: 10.1002/art.1780190214. [DOI] [PubMed] [Google Scholar]
  3. Alspaugh M. A., Tan E. M. Antibodies to cellular antigens in Sjögren's syndrome. J Clin Invest. 1975 May;55(5):1067–1073. doi: 10.1172/JCI108007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Aslpaugh M. A., Tan E. M. Serum antibody in rheumatoid arthritis reactive with a cell-associated antigen. Demonstration by precipitation and immunofluorescence. Arthritis Rheum. 1976 Jul-Aug;19(4):711–719. doi: 10.1002/1529-0131(197607/08)19:4<711::aid-art1780190409>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  5. Catalano M. A., Carson D. A., Slovin S. F., Richman D. D., Vaughan J. H. 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 Nov;76(11):5825–5828. doi: 10.1073/pnas.76.11.5825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cremer N. E., Hurwitz D., Quismorio F. P., Lennette E. H., Friou G. J. Antiviral antibodies in rheumatoid synovial fluid and cryoprecipitates. Clin Exp Immunol. 1974 Sep;18(1):27–37. [PMC free article] [PubMed] [Google Scholar]
  7. Elson C. J., Crawford D. H., Bucknall R. C., Allen C., Thompson J. L., Epstein M. A., Hall N. D., Bacon P. A. Infection with E.B. virus and rheumatoid arthritis. Lancet. 1979 Jan;1(8107):105–105. doi: 10.1016/s0140-6736(79)90096-5. [DOI] [PubMed] [Google Scholar]
  8. Henle G., Henle W. Immunofluorescence in cells derived from Burkitt's lymphoma. J Bacteriol. 1966 Mar;91(3):1248–1256. doi: 10.1128/jb.91.3.1248-1256.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Henle G., Henle W., Klein G. Demonstration of two distinct components in the early antigen complex of Epstein-Barr virus-infected cells. Int J Cancer. 1971 Sep 15;8(2):272–282. doi: 10.1002/ijc.2910080212. [DOI] [PubMed] [Google Scholar]
  10. Henle G., Lennette E. T., Alspaugh M. A., Henle W. Rheumatoid factor as a cause of positive reactions in tests for Epstein-Barr virus-specific IgM antibodies. Clin Exp Immunol. 1979 Jun;36(3):415–422. [PMC free article] [PubMed] [Google Scholar]
  11. Lennette E. T., Lennette D. A. Immune adherence hemagglutination: alternative to complement-fixation serology. J Clin Microbiol. 1978 Mar;7(3):282–285. doi: 10.1128/jcm.7.3.282-285.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Phillips P. E., Waxman J., Hirshaut Y., Kaplan M. H. Virus antibody levels and delayed hypersensitivity in rheumatoid arthritis. Ann Rheum Dis. 1976 Apr;35(2):152–154. doi: 10.1136/ard.35.2.152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Reedman B. M., Klein G. Cellular localization of an Epstein-Barr virus (EBV)-associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines. Int J Cancer. 1973 May;11(3):499–520. doi: 10.1002/ijc.2910110302. [DOI] [PubMed] [Google Scholar]
  14. Rothfield N. F., Evans A. S., Niederman J. C. Clinical and laboratory aspects of raised virus antibody titres in systemic lupus erythematosus. Ann Rheum Dis. 1973 May;32(3):238–246. doi: 10.1136/ard.32.3.238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Stevens D. A., Stevens M. B., Newell G. R., Levine P. H., Waggoner D. E. Epstein-Barr virus (herpes-type virus) antibodies in connective tissue diseases. Arch Intern Med. 1972 Jul;130(1):23–28. [PubMed] [Google Scholar]

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