Wood Rebecca A, Guthridge Lauren, Thurmond Emma, Guthridge Carla J, Kheir Joseph M, Bourn Rebecka L, Wagner Catriona A, Chen Hua, DeJager Wade, Macwana Susan R, Kamp Stan, Lu Rufei, Arriens Cristina, Chakravarty Eliza F, Thanou Aikaterini, Merrill Joan T, Guthridge Joel M, James Judith A
Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.
Departments of Medicine and Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
J Transl Autoimmun. 2021 Aug 31;4:100117. doi: 10.1016/j.jtauto.2021.100117. eCollection 2021.
SLE is a clinically heterogeneous disease characterized by an unpredictable relapsing-remitting disease course. Although the etiology and mechanisms of SLE flares remain elusive, Epstein-Barr virus (EBV) reactivation is implicated in SLE pathogenesis. This study examined the relationships between serological measures of EBV reactivation, disease activity, and interferon (IFN)-associated immune pathways in SLE patients. Sera from adult SLE patients (n = 175) and matched unaffected controls (n = 47) were collected and tested for antibodies against EBV-viral capsid antigen (EBV-VCA; IgG and IgA), EBV-early antigen (EBV-EA; IgG), cytomegalovirus (CMV; IgG), and herpes simplex virus (HSV-1; IgG). Serological evidence of EBV reactivation was more common in SLE patients compared to controls as demonstrated by seropositivity to EBV-EA IgG (39% vs 13%; p = 0.0011) and EBV-VCA IgA (37% vs 17%; p = 0.018). EBV-VCA, CMV1, and HSV-1 IgG seropositivity rates did not differ between SLE patients and controls. Furthermore, concentrations of EBV-VCA (IgG and IgA) and EBV-EA (IgG) were higher in SLE patients. SLE patients with high disease activity had increased concentrations of EBV-VCA IgA (mean ISR 1.34 vs. 0.97; p = 0.041) and EBV-EA IgG levels (mean ISR 1.38 vs. 0.90; p = 0.007) compared with those with lower disease activity. EBV reactivation was associated with enhanced levels of the IFN-associated molecule IP-10 (p < 0.001) and the soluble mediators BLyS (p < 0.001) and IL-10 (p = 0.0011). In addition, EBV-EA IgG responses were enriched in two previously defined patient clusters with robust expression of IFN and inflammatory or lymphoid and monocyte responses. Patients in these clusters were also more likely to have major organ involvement, such as renal disease. This study supports a possible role for EBV reactivation in SLE disease activity.
系统性红斑狼疮（SLE）是一种临床异质性疾病，其特征为疾病进程不可预测，呈复发-缓解型。尽管SLE病情活动的病因和机制仍不清楚，但爱泼斯坦-巴尔病毒（EBV）再激活与SLE发病机制有关。本研究探讨了SLE患者中EBV再激活的血清学指标、疾病活动度以及干扰素（IFN）相关免疫途径之间的关系。收集了成年SLE患者（n = 175）和配对的未受影响对照者（n = 47）的血清，检测抗EBV病毒衣壳抗原（EBV-VCA；IgG和IgA）、EBV早期抗原（EBV-EA；IgG）、巨细胞病毒（CMV；IgG）和单纯疱疹病毒1型（HSV-1；IgG）的抗体。与对照组相比，EBV再激活的血清学证据在SLE患者中更常见，EBV-EA IgG血清阳性率（39%对13%；p = 0.0011）和EBV-VCA IgA血清阳性率（37%对17%；p = 0.018）表明了这一点。SLE患者和对照组之间EBV-VCA、CMV1和HSV-1 IgG血清阳性率没有差异。此外，SLE患者中EBV-VCA（IgG和IgA）和EBV-EA（IgG）的浓度更高。与疾病活动度较低的SLE患者相比，疾病活动度高的SLE患者EBV-VCA IgA浓度升高（平均ISR 1.34对0.97；p = 0.041），EBV-EA IgG水平升高（平均ISR 1.38对0.90；p = 0.007）。EBV再激活与IFN相关分子IP-10水平升高（p < 0.001）、可溶性介质B淋巴细胞刺激因子（BLyS，p < 0.001）和白细胞介素10（IL-10，p = 0.0011）有关。此外，EBV-EA IgG反应在两个先前定义的患者亚组中富集，这两个亚组具有强大的IFN表达以及炎症或淋巴细胞和单核细胞反应。这些亚组中的患者也更有可能出现主要器官受累，如肾脏疾病。本研究支持EBV再激活在SLE疾病活动中可能发挥的作用。
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