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Epidemiology and outcomes
Original research article
Strong viral associations with SLE among Filipinos
  1. Evan S Vista1,2,
  2. Michael H Weisman3,
  3. Mariko L Ishimori3,
  4. Hua Chen2,
  5. Rebecka L Bourn2,
  6. Ben F Bruner2,4,
  7. Laniyati Hamijoyo1,
  8. Robelle D Tanangunan1,
  9. Noga J Gal3,
  10. Julie M Robertson2,
  11. John B Harley5,6,
  12. Joel M Guthridge2,
  13. Sandra V Navarra1 and
  14. Judith A James2,7
  1. 1 Section of Rheumatology, University of Santo Tomas Hospital, Manila, Philippines
  2. 2 Arthritis & Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
  3. 3 Department of Medicine, Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, California, USA
  4. 4 Department of Biology, Harding University, Searcy, Arkansas, USA
  5. 5 Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
  6. 6 Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA
  7. 7 Departments of Medicine and Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
  1. Correspondence to Dr Judith A James; judith-james{at}omrf.org

Abstract

Objectives Epstein-Barr virus (EBV) is considered an important environmental factor in SLE aetiology, but the relationship between SLE and EBV in the Filipino population is unknown. We tested associations between SLE, lupus-associated autoantibodies and seropositivity for EBV and other herpes viruses in the Filipino population.

Methods Sera from Filipino patients with SLE (n=233), unaffected first-degree relatives (FDRs, n=543) and unrelated controls (n=221) were tested for antibodies against EBV, cytomegalovirus (CMV) and herpes simplex viruses (HSV-1 and HSV-2) by standardised ELISAs. Humoral specificity against EBV nuclear antigen (EBNA)-1 was compared by solid-phase epitope mapping. Autoantibodies were detected by a bead-based multiplex assay. Results were analysed by Fisher's exact test, Student's t-test, χ2 test and one-way analysis of variance, as appropriate for the question.

Results Filipino patients with SLE had increased seroprevalence and elevated antibody concentrations against EBV viral capsid antigen (EBV-VCA), CMV, HSV-1 and HSV-2 compared with unrelated controls (p<0.05). Seropositivity for anti-EBV early antigen (EA), a marker of EBV reactivation, was dramatically increased in patients with SLE compared with unrelated controls (92.3% vs 40.4%; OR 17.15(95% CI 10.10, 30.66), p<0.0001) or unaffected FDRs (49.4%; OR 12.04(7.42, 20.74), p<0.0001), despite similar seroprevalence of EBV-VCA in patients and FDRs. In patients with SLE, EBV-EA seropositivity correlated with lupus-associated autoantibodies (p<0.001), most notably with autoantibodies against dsDNA, chromatin, Sm, SmRNP and RNP A (p<0.01). Patient and unrelated control sera reacted to the highly repetitive glycine and alanine domain of EBNA-1. An epitope spanning EBNA-1410-420 was identified in sera of patients with SLE and showed limited binding by FDR and control sera.

Conclusions Filipino patients with SLE have elevated prevalence and concentrations of antibodies against EBV, CMV, HSV-1 and HSV-2 antigens, along with altered anti-EBNA-1 specificities. EBV reactivation is more common among Filipino patients with SLE compared with healthy Filipinos and may contribute to SLE pathogenesis in this population.

  • systemic lupus erythematosus
  • infections
  • autoimmunity

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/lupus-2017-000214

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    Footnotes

    • Contributors EV, JBH, JMG, SVN and JAJ designed the study. EV, MHW, MLI, LH, RBT, NJG, JMR, JBH, JMG, SVN and JAJ acquired data. EV, HC, RLB, BFB, JMR, JMG, SVN and JAJ analysed and/or interpreted data. All authors assisted with the development of the manuscript and gave final approval of the version to be published. JAJ had final responsibility for the decision to submit for publication.

    • Funding The authors acknowledge the following grant support: P30 AR053483, U01 AI101934, U19 AI082714, U54 GM104938, P30 GM103510, U01 AI130830, R01 AI024717, U01 HG008666, P30 AR070549.

    • Competing interests None declared.

    • Patient consent The results presented are aggregated results, with no identifying information. All study participants provided appropriate written, informed consent prior to beginning study-specific procedures.

    • Ethics approval The Institutional Review Boards of the Oklahoma Medical Research Foundation, University of Santo Tomas Hospital and Cedars-Sinai Medical Center.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement All relevant data for this study are being published. Please contact the corresponding author with any additional requests, which will be processed through the Oklahoma Rheumatic Disease Research Cores Center.