Humoral markers of active Epstein–Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus

Abstract

We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients and 29 healthy controls using ELISAs. Regression analyses and univariate comparisons were performed for associative evaluation between virus serology, plasma galectin-3 binding protein and autoantibodies, along with other clinical and demographic parameters. Plasma galectin-3 binding protein concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P = 0.02 and P = 0.002, respectively). Furthermore, systemic lupus erythematosus patients with anti-extractable nuclear antigens had significantly higher antibody levels against Epstein-Barr virus early antigen diffuse (P = 0.02). Our study supports a link between active Epstein-Barr virus infections, positivity for anti-extractable nuclear antigens and increased plasma galectin-3 binding protein concentrations/type I interferon activity in systemic lupus erythematosus patients.

Key genes and functional coexpression modules involved in the pathogenesis of systemic lupus erythematosus

“…Some studies have proposed that viral infections can result in increased expressions of genes involving type I IFN system, which may further lead to SLE (Buskiewicz et al, 2016;Moal et al, 2013;Slight-Webb, Bagavant, Crowe, & James, 2015). There are also some observational studies on the link between virus infections and SLE (Hanlon, Avenell, Aucott, & Vickers, 2014;Rasmussen, Nielsen, Houen, & Jacobsen, 2016;Zandman-Goddard et al, 2009 Guiducci, & Coffman, 2007;Fagone, Muthumani, et al, 2014;Oon, Wilson, & Wicks, 2016). Some studies find that vaccinations against virus infections can also increase risk of SLE (Agmon-Levin et al, 2014;Geier & Geier, 2017;Wang, Shao, Wang, Xu, & Zhang, 2017), which further provides some evidence for et al, 1996;Gröndal et al, 2000).…”

Strong viral associations with SLE among Filipinos

“… 50–52 Similarly, anti-EBV-EA responses in patients with SLE were recently correlated with autoantibodies against extractable nuclear antigens and with plasma galectin-3 binding protein, a marker of type I interferon responses. 53 In addition to stimulating type I interferon that may support autoantibody production, 54 55 EBV infection increases exposure to potentially cross-reactive viral antigens, such as EBNA-1. 14 38 56 …”

Galectin-3-binding protein: A multitask glycoprotein with innate immunity functions in viral and bacterial infections

“…Also hantavirus infection of HUVECs up‐regulates Gal‐3BP at transcriptional level . Most recently, increased Gal‐3BP concentrations were reported to occur in ongoing/recently active Epstein‐Barr virus infection . Denard and coauthors identified Gal‐3BP as an interaction partner for recombinant adeno‐associated virus 6 (rAAV‐6), when they were looking for potential nonimmunoglobulin neutralizing factors from human serum .…”

“…82 Most recently, increased Gal-3BP concentrations were reported to occur in ongoing/recently active Epstein-Barr virus infection. 10 Denard and coauthors identified Gal-3BP as an interaction partner for recombinant adeno-associated virus 6 (rAAV-6), when they were looking for potential nonimmunoglobulin neutralizing factors from human serum. 83 The authors found out that human, but not mouse, Gal-3BP efficiently bound rAAV-6 and was also able to interact with rAAV-1 and -5.…”

“…High serum concentrations of Gal‐3BP were detected early on in patients infected with HIV and hepatitis virus, and more recently in patients infected with dengue virus (DENV), Epstein–Barr virus, and Puumala hantavirus . One recent report describes elevated serum Gal‐3BP concentrations in patients suffering from blood‐culture positive bacterial infections .…”