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

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.

journal_name

Ann Rheum Dis

authors

Jog NR,Young KA,Munroe ME,Harmon MT,Guthridge JM,Kelly JA,Kamen DL,Gilkeson GS,Weisman MH,Karp DR,Gaffney PM,Harley JB,Wallace DJ,Norris JM,James JA

doi

10.1136/annrheumdis-2019-215361

subject

Has Abstract

pub_date

2019-09-01 00:00:00

pages

1235-1241

issue

9

eissn

0003-4967

issn

1468-2060

pii

annrheumdis-2019-215361

journal_volume

78

pub_type

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