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Evidence that autoantibody production may be driven by acute Epstein-Barr virus infection in Sjögren’s disease
  1. Erin Hudson1,
  2. Lijun Yang2,
  3. Elizabeth K Chu1,
  4. Haoyang Zhuang1,
  5. Rawad Daniel Arja1,
  6. Blas Y Betancourt1,
  7. Indraneel Bhattacharyya3,
  8. Shuhong Han1,
  9. Seunghee Cha4,
  10. Edward K L Chan5,
  11. Mathew Sebastian6,
  12. Carolyn Stalvey7,
  13. Marvin J Fritzler8,
  14. Westley H Reeves1
  1. 1Division of Rheumatology and Clinical Immunology, University of Florida Health Science Center, Gainesville, Florida, USA
  2. 2Pathology, University of Florida Health Science Center, Gainesville, Florida, USA
  3. 3University of Florida College of Dentistry, Gainesville, Florida, USA
  4. 4Oral Medicine, University of Florida, Gainesville, Florida, USA
  5. 5Oral Biology, Anatomy and Cell Biology, University of Florida Health Science Center, Gainesville, Florida, USA
  6. 6Department of Medicine, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA
  7. 7University of Florida, Gainesville, Florida, USA
  8. 8Department of Medicine, University of Calgary, Calgary, Alberta, Canada
  1. Correspondence to Dr Westley H Reeves; whreeves{at}ufl.edu

Abstract

Objectives Sjögren’s disease (SD) is an autoimmune disease affecting the exocrine glands that is associated with autoantibodies against Ro60/SS-A, anti-Ro52/TRIM21, La/SS-B and others. We examined the role of acute Epstein-Barr virus (EBV) infection in the pathogenesis of these autoantibodies in a previously healthy patient (patient 1) with primary EBV infection who developed SD with anti-Ro/La and anti-Smith/U1 ribonucleoprotein (Sm/U1RNP) autoantibodies and had lymphoplasmacytic foci on labial salivary gland biopsy.

Methods Immune responses to Epstein-Barr nuclear antigen-1 (EBNA1) and the Ro52/Ro60/La and Sm/U1RNP autoantigens and peptides were examined by immunoassay in patient 1, healthy and disease controls.

Results Anti-Ro52 and anti-Ro60 autoantibodies were present 7 days after primary infection and underwent IgM to IgG switching, suggesting that EBV infection promoted their production. More than 7 months after primary infection, new and increasing levels of antibodies against EBNA1 and the U1RNP autoantigen appeared concomitantly. These antibodies bound homologous peptide sequences shared by EBNA1, SmB′ and the U1-C (U1RNP) protein, consistent with induction by molecular mimicry. Although Ro60 and EBNA1 crossreact immunologically, we found that anti-Ro60/anti-Ro52 antibody production was stimulated by acute EBV infection long before the onset of anti-EBNA1. Unexpectedly, a subset of healthy control sera had anti-SmB′ peptide antibodies that were not correlated with anti-EBNA1 peptide antibodies. In contrast, anti-SmB′ and EBNA1 peptide antibody levels correlated in anti-Sm/U1RNP+ lupus sera.

Conclusions Primary EBV infection can promote anti-Ro60/anti-Ro52 and anti-U1RNP responses, though by different mechanisms. Some healthy individuals produce anti-SmB′ peptide autoantibodies independently of a response to EBNA1.

  • Autoantibodies
  • Autoimmune Diseases
  • Autoimmunity
  • Sjogren's Syndrome

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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Footnotes

  • Handling editor Josef S Smolen

  • Contributors Data collection and analysis was performed by EH, LY, HZ, RDA, IB, SH, MJF and WHR. Clinical evaluation was performed by EKC, BYB, SC, MS, CS and WHR. The first draft of the manuscript was written by EH and WHR with editing by LJY, EKLC and MJF. All authors commented on subsequent versions of the manuscript and approved the final manuscript. WHR is responsible for the overall content as guarantor.

  • Funding Supported by NIH/NIAMS grant R01-AR44731 (WHR), AR079693 (SC) and the Department of Medicine (HZ).

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

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