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. 2024 Oct 29:ard-2024-226226.
doi: 10.1136/ard-2024-226226. Online ahead of print.

Evidence that autoantibody production may be driven by acute Epstein-Barr virus infection in Sjögren's disease

Erin Hudson  1 , Lijun Yang  2 , Elizabeth K Chu  1 , Haoyang Zhuang  1 , Rawad Daniel Arja  1 , Blas Y Betancourt  1 , Indraneel Bhattacharyya  3 , Shuhong Han  1 , Seunghee Cha  4 , Edward K L Chan  5 , Mathew Sebastian  6 , Carolyn Stalvey  7 , Marvin J Fritzler  8 , Westley H Reeves  9
Affiliations

Evidence that autoantibody production may be driven by acute Epstein-Barr virus infection in Sjögren's disease

Erin Hudson et al. Ann Rheum Dis. .

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.

Keywords: Autoantibodies; Autoimmune Diseases; Autoimmunity; Sjogren's Syndrome.

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Conflict of interest statement

Competing interests: None declared.

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