Association of Epstein-Barr Virus Serological Reactivation with Transitioning to Systemic Lupus Erythematosus in At-risk Individuals

Overview

Journal Ann Rheum Dis

Specialty Rheumatology

Date 2019 Jun 21

PMID 31217170

Citations 38

Authors

Neelakshi R Jog

Kendra A Young

Melissa E Munroe

Michael T Harmon

Joel M Guthridge

Jennifer A Kelly

Diane L Kamen

Gary S Gilkeson

Michael H Weisman

David R Karp

Patrick M Gaffney

John B Harley

Daniel J Wallace

Jill M Norris

Judith A James

Affiliations

Soon will be listed here.

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 , , and 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 variant rs48100485 and VCA IgG levels and 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.

Citing Articles

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