Increased Epstein-Barr Virus DNA Load and Antibodies Against EBNA1 and EA in Sardinian Patients with Rheumatoid Arthritis
Increased Epstein-Barr Virus DNA Load and Antibodies Against EBNA1 and EA in Sardinian Patients with Rheumatoid Arthritis
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DOI：
10.1089/vim.2015.0035
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发表时间：
2015-09-01
期刊：
影响因子：
2.2
通讯作者：
Sechi, Leonardo Antonio
中科院分区：
文献类型：
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作者：
Erre, Gian Luca;Mameli, Giuseppe;Sechi, Leonardo Antonio
爱泼斯坦-巴尔病毒(EBV)感染在包括类风湿关节炎(RA)在内的自身免疫性疾病的病因学中的作用一直被认为。然而，关于撒丁岛人群中RA患者EBV负担的数据尚未报道，撒丁岛人群是一种自身免疫性疾病发病率很高的基因分离株。135，撒丁岛受试者(77名RA患者和58名人口学匹配的健康献血者)参加了一项横断面病例对照研究。采用实时定量聚合酶链式反应检测外周血单个核细胞(PBMC)中的EBV-DNA。用免疫酶标法检测抗早期抗原Ig G(抗EA-Ig G)和抗EB病毒核抗原1 Ig G(抗EBNA-1 Ig G)的流行率和滴度。RA患者EBVDNA阳性率明显高于HD患者(分别为79.2%和56.9%，P=0.008)。类似地，RA组的EBV相对载量高于HD组[2.83(6.5)对0.53(1)2(-Ct)EBV-DNA，p=0.02]。此外，撒丁岛RA患者中，抗EBNA-1Ig G抗体(90%比HD组仅69%，p=0.006)和抗EA Ig G抗体(37%比HD组仅10.3%，p=0.002)升高。亚群分析显示，接受抗IL-6受体单抗Tocilizumab治疗的RA患者PBMC的EBV病毒载量显著低于其他免疫抑制剂治疗的RA患者PBMC(p=0.03)。这些数据表明在撒丁岛人群中EB病毒感染和类风湿关节炎之间存在关联。IL-6抑制对RA患者EBV病毒载量的潜在影响应在前瞻性试验中进一步探讨。
A role for Epstein-Barr Virus (EBV) infection in the etiology of autoimmune diseases, including rheumatoid arthritis (RA), has long been suggested. However, data about EBV burden in RA patients from Sardinian population, a genetic isolate with high prevalence of autoimmune diseases, have not yet been reported. One hundred thirty-five, Sardinian subjects (77 RA patients and 58 demographically matched healthy donors, HDs) were enrolled in a cross-sectional case-control study. EBV-DNA was quantified by quantitative real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMCs). Prevalence and titers of anti-Early Antigen IgG (anti-EA-IgG) and anti-Epstein-Barr Nuclear Antigen 1 IgG (anti-EBNA-1 IgG) were determined by immunoenzimatic assay. EBV-DNA positivity was more frequent in RA PBMCs than in HD PBMCs (79.2% vs. 56.9% respectively, p=0.008). Similarly EBV relative load was increased in RA than in HD PBMCs [2.83 (6.5) vs. 0.53 (1) 2(-Ct) EBV-DNA, respectively, p=0.02]. Moreover, Sardinian RA patients were found to have increased prevalence of anti-EBNA-1 IgG (90% vs. only 69% of HD, p=0.006) and anti-EA IgG (37% compared with only 10.3% of HD, p=0.002). Subgroup analysis revealed that PBMCs from RA receiving Tocilizumab, an anti-interleukin-6 (IL-6) receptor monoclonal inhibitor, have significantly lower EBV viral loads in comparison to PBMCs from RA under other immunosuppressors (p=0.03). These data suggest an association between EBV infection and RA in the Sardinian population. The potential influence of IL-6 inhibition on EBV viral load in RA patients should be further explored in prospective trials.