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Association of Epstein-Barr virus with systemic lupus erythematosus: effect modification by race, age, and cytotoxic T lymphocyte-associated antigen 4 genotype.

Publication ,  Journal Article
Parks, CG; Cooper, GS; Hudson, LL; Dooley, MA; Treadwell, EL; St Clair, EW; Gilkeson, GS; Pandey, JP
Published in: Arthritis Rheum
April 2005

OBJECTIVE: Epstein-Barr virus (EBV) is hypothesized to play a role in the development of systemic lupus erythematosus (SLE). Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is important in regulating T cell-mediated immunity, encompassing the first line of response to viral infections, and genetic variation in CTLA-4 has been associated with SLE. This study examined the seroprevalence of EBV in a population-based study of SLE patients from the southeastern United States, and potential interactions with CTLA-4 polymorphisms were assessed. METHODS: Cases comprised 230 subjects recently diagnosed as having SLE (144 African American and 86 white) from university and community-based clinics, and controls comprised 276 age-, sex-, and state-matched subjects (72 African American and 204 white) recruited from driver's license registries. Antibodies to EBV capsid antigen were determined by enzyme-linked immunosorbent assay, with results expressed as positive or negative using the international standardized ratio (ISR) (a ratio of the sample absorbance to a known standard). CTLA-4 genotypes were identified by polymerase chain reaction-based methods. RESULTS: In African Americans, EBV-IgA seroprevalence was strongly associated with SLE (odds ratio [OR] 5.6, 95% confidence interval [95% CI] 3.0-10.6). In whites, the modest association of SLE with EBV-IgA (OR 1.6) was modified by age, in that the strongest association was observed in those older than age 50 years (OR 4.1, 95% CI 1.6-10.4). The seroprevalence of EBV-IgM and that of EBV-IgG were not associated with SLE. Higher EBV-IgG absorbance ratios were observed in SLE patients, with a significant dose response across units of the ISR in African Americans (P < 0.0001). Allelic variation in the CTLA-4 gene promoter (-1661A/G) significantly modified the association between SLE and EBV-IgA (P = 0.03), with a stronger association among those with the -1661AA genotype. CONCLUSION: These findings suggest that repeated or reactivated EBV infection, which results in increased EBV-IgA seroprevalence and higher IgG antibody titers, may be associated with SLE, and that the CTLA-4 genotype influences immune responsiveness to EBV in SLE patients. The observed patterns of effect modification by race, age, and CTLA-4 genotype should be examined in other studies and may help frame new hypotheses regarding the role of EBV in SLE etiology.

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Published In

Arthritis Rheum

DOI

ISSN

0004-3591

Publication Date

April 2005

Volume

52

Issue

4

Start / End Page

1148 / 1159

Location

United States

Related Subject Headings

  • White People
  • South Carolina
  • North Carolina
  • Middle Aged
  • Male
  • Lupus Erythematosus, Systemic
  • Humans
  • Herpesvirus 4, Human
  • Genotype
  • Genetic Predisposition to Disease
 

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Parks, C. G., Cooper, G. S., Hudson, L. L., Dooley, M. A., Treadwell, E. L., St Clair, E. W., … Pandey, J. P. (2005). Association of Epstein-Barr virus with systemic lupus erythematosus: effect modification by race, age, and cytotoxic T lymphocyte-associated antigen 4 genotype. Arthritis Rheum, 52(4), 1148–1159. https://doi.org/10.1002/art.20997
Parks, Christine G., Glinda S. Cooper, Lori L. Hudson, Mary Anne Dooley, Edward L. Treadwell, E. W. St Clair, Gary S. Gilkeson, and Janardan P. Pandey. “Association of Epstein-Barr virus with systemic lupus erythematosus: effect modification by race, age, and cytotoxic T lymphocyte-associated antigen 4 genotype.Arthritis Rheum 52, no. 4 (April 2005): 1148–59. https://doi.org/10.1002/art.20997.
Parks CG, Cooper GS, Hudson LL, Dooley MA, Treadwell EL, St Clair EW, et al. Association of Epstein-Barr virus with systemic lupus erythematosus: effect modification by race, age, and cytotoxic T lymphocyte-associated antigen 4 genotype. Arthritis Rheum. 2005 Apr;52(4):1148–59.
Parks, Christine G., et al. “Association of Epstein-Barr virus with systemic lupus erythematosus: effect modification by race, age, and cytotoxic T lymphocyte-associated antigen 4 genotype.Arthritis Rheum, vol. 52, no. 4, Apr. 2005, pp. 1148–59. Pubmed, doi:10.1002/art.20997.
Parks CG, Cooper GS, Hudson LL, Dooley MA, Treadwell EL, St Clair EW, Gilkeson GS, Pandey JP. Association of Epstein-Barr virus with systemic lupus erythematosus: effect modification by race, age, and cytotoxic T lymphocyte-associated antigen 4 genotype. Arthritis Rheum. 2005 Apr;52(4):1148–1159.
Journal cover image

Published In

Arthritis Rheum

DOI

ISSN

0004-3591

Publication Date

April 2005

Volume

52

Issue

4

Start / End Page

1148 / 1159

Location

United States

Related Subject Headings

  • White People
  • South Carolina
  • North Carolina
  • Middle Aged
  • Male
  • Lupus Erythematosus, Systemic
  • Humans
  • Herpesvirus 4, Human
  • Genotype
  • Genetic Predisposition to Disease