Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
Department of Epidemiology, University of Colorado Anschutz Medical Campus, Colorado School of Public Health, Aurora, Colorado, USA.
Ann Rheum Dis. 2019 Sep;78(9):1235-1241. doi: 10.1136/annrheumdis-2019-215361. Epub 2019 Jun 19.
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.
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.
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.
Heightened serologic reactivation of EBV increases the probability of transitioning to SLE in unaffected SLE relatives.
系统性红斑狼疮（SLE）是一种病因不明的全身性自身免疫性疾病。EB 病毒（EBV）是一种与 SLE 相关的环境因素。EBV 通过针对病毒衣壳抗原（VCA）和早期抗原（EA）的抗体频繁激活来维持潜伏状态。在这项研究中，我们确定 EBV 再激活和 EBV 相关宿主基因中的单核苷酸多态性（SNP）是否与 SLE 转变有关。
在 6.3（±3.9）年后，重新联系未在基线时患有 SLE 的 SLE 患者亲属（n=436），并评估其 SLE 期间的过渡（≥4 项累积美国风湿病学会标准）；56（13%）在随访前过渡到 SLE。在两次就诊时，均获得详细的人口统计学、环境、临床信息和血液样本。通过 ELISA 测定针对病毒抗原的抗体。通过 ImmunoChip 对 、 、 和 基因中的 SNP 进行分型。使用广义估计方程检验病毒抗体水平与向 SLE 过渡之间的关联。
与自身抗体阴性未过渡亲属相比，过渡者的基线 VCA IgG（4.879±1.797 与 3.866±1.795，p=0.0003）和 EA IgG（1.192±1.113 与 0.7774±0.8484，p=0.0236）水平更高。VCA IgG 和 EA IgG 的增加与 SLE 过渡有关（OR 1.28 95%CI 1.07 至 1.53，p=0.007，OR 1.43 95%CI 1.06 至 1.93，p=0.02，分别）。在向 SLE 过渡中，观察到 变体 rs48100485 与 VCA IgG 水平和 变体 rs3024493 与 VCA IgA 水平之间存在显著的相互作用。
未受影响的 SLE 亲属中 EBV 的血清再激活增加了向 SLE 过渡的可能性。
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