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Ann Rheum Dis. 2019 Sep;78(9):1235-1241. doi: 10.1136/annrheumdis-2019-215361. Epub 2019 Jun 19.

Association of Epstein-Barr virus serological reactivation with transitioning to systemic lupus erythematosus in at-risk individuals.

Author information

1
Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
2
Department of Epidemiology, University of Colorado Anschutz Medical Campus, Colorado School of Public Health, Aurora, Colorado, USA.
3
Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
4
Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
5
Division of Rheumatic Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
6
Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
7
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States.
8
US Department of Veterans Affairs Medical Center, Cincinnati, OH, United States.
9
Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA judith-james@omrf.org.
10
Departments of Medicine and Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.

Abstract

OBJECTIVE:

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with unknown aetiology. Epstein-Barr virus (EBV) is an environmental factor associated with SLE. EBV maintains latency in B cells with frequent reactivation measured by antibodies against viral capsid antigen (VCA) and early antigen (EA). In this study, we determined whether EBV reactivation and single nucleotide polymorphisms (SNPs) in EBV-associated host genes are associated with SLE transition.

METHODS:

SLE patient relatives (n=436) who did not have SLE at baseline were recontacted after 6.3 (±3.9) years and evaluated for interim transitioning to SLE (≥4 cumulative American College of Rheumatology criteria); 56 (13%) transitioned to SLE prior to the follow-up visit. At both visits, detailed demographic, environmental, clinical information and blood samples were obtained. Antibodies against viral antigens were measured by ELISA. SNPs in IL10, CR2, TNFAIP3 and CD40 genes were typed by ImmunoChip. Generalised estimating equations were used to test associations between viral antibody levels and transitioning to SLE.

RESULTS:

Mean baseline VCA IgG (4.879±1.797 vs 3.866±1.795, p=0.0003) and EA IgG (1.192±1.113 vs 0.7774±0.8484, p=0.0236) levels were higher in transitioned compared with autoantibody negative non-transitioned relatives. Increased VCA IgG and EA IgG were associated with transitioning to SLE (OR 1.28 95% CI 1.07 to 1.53, p=0.007, OR 1.43 95% CI 1.06 to 1.93, p=0.02, respectively). Significant interactions were observed between CD40 variant rs48100485 and VCA IgG levels and IL10 variant rs3024493 and VCA IgA levels in transitioning to SLE.

CONCLUSION:

Heightened serologic reactivation of EBV increases the probability of transitioning to SLE in unaffected SLE relatives.

KEYWORDS:

autoimmunity; epstein-barr virus; systemic lupus erythematosus

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