Strong viral associations with SLE among Filipinos.
Strong viral associations with SLE among Filipinos.
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DOI：
10.1136/lupus-2017-000214
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发表时间：
2017
影响因子：
3.9
通讯作者：
James JA
中科院分区：
文献类型：
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作者：
Vista ES;Weisman MH;Ishimori ML;Chen H;Bourn RL;Bruner BF;Hamijoyo L;Tanangunan RD;Gal NJ;Robertson JM;Harley JB;Guthridge JM;Navarra SV;James JA
Epstein-Barr 病毒 (EBV) 被认为是 SLE 病因学中的重要环境因素，但菲律宾人群中 SLE 和 EBV 之间的关系尚不清楚。我们测试了菲律宾人群中 SLE、狼疮相关自身抗体与 EBV 和其他疱疹病毒血清阳性之间的关联。通过标准化 ELISA，对菲律宾 SLE 患者 (n=233)、未受影响的一级亲属 (FDR，n=543) 和无关对照 (n=221) 的血清进行了 EBV、巨细胞病毒 (CMV) 和单纯疱疹病毒（HSV-1 和 HSV-2）抗体检测。通过固相表位作图比较针对 EBV 核抗原 (EBNA)-1 的体液特异性。通过基于珠子的多重测定检测自身抗体。根据问题的情况，通过 Fisher 精确检验、Student t 检验、χ2 检验和单向方差分析对结果进行分析。与无关对照相比，菲律宾 SLE 患者的血清阳性率升高，针对 EBV 病毒衣壳抗原 (EBV-VCA)、CMV、HSV-1 和 HSV-2 的抗体浓度升高 (p<0.05)。与无关对照（92.3% vs 40.4%；OR 17.15（95% CI 10.10, 30.66），p<0.0001）或未受影响的 FDR（49.4%；OR 12.04（7.42， 20.74), p<0.0001)，尽管患者和 FDR 中 EBV-VCA 的血清阳性率相似。在 SLE 患者中，EBV-EA 血清阳性与狼疮相关自身抗体相关 (p<0.001)，最显着的是与抗 dsDNA、染色质、Sm、SmRNP 和 RNP A 的自身抗体相关 (p<0.01)。患者和无关的对照血清对 EBNA-1 的高度重复的甘氨酸和丙氨酸结构域产生反应。在 SLE 患者的血清中鉴定出跨越 EBNA-1410-420 的表位，并显示 FDR 和对照血清的结合有限。菲律宾系统性红斑狼疮患者的 EBV、CMV、HSV-1 和 HSV-2 抗原抗体的患病率和浓度均升高，并且抗 EBNA-1 特异性发生改变。与健康菲律宾人相比，EBV 再激活在菲律宾 SLE 患者中更为常见，并且可能与该人群的 SLE 发病机制有关。
Epstein-Barr virus (EBV) is considered an important environmental factor in SLE aetiology, but the relationship between SLE and EBV in the Filipino population is unknown. We tested associations between SLE, lupus-associated autoantibodies and seropositivity for EBV and other herpes viruses in the Filipino population. Sera from Filipino patients with SLE (n=233), unaffected first-degree relatives (FDRs, n=543) and unrelated controls (n=221) were tested for antibodies against EBV, cytomegalovirus (CMV) and herpes simplex viruses (HSV-1 and HSV-2) by standardised ELISAs. Humoral specificity against EBV nuclear antigen (EBNA)-1 was compared by solid-phase epitope mapping. Autoantibodies were detected by a bead-based multiplex assay. Results were analysed by Fisher's exact test, Student's t-test, χ2 test and one-way analysis of variance, as appropriate for the question. Filipino patients with SLE had increased seroprevalence and elevated antibody concentrations against EBV viral capsid antigen (EBV-VCA), CMV, HSV-1 and HSV-2 compared with unrelated controls (p<0.05). Seropositivity for anti-EBV early antigen (EA), a marker of EBV reactivation, was dramatically increased in patients with SLE compared with unrelated controls (92.3% vs 40.4%; OR 17.15(95% CI 10.10, 30.66), p<0.0001) or unaffected FDRs (49.4%; OR 12.04(7.42, 20.74), p<0.0001), despite similar seroprevalence of EBV-VCA in patients and FDRs. In patients with SLE, EBV-EA seropositivity correlated with lupus-associated autoantibodies (p<0.001), most notably with autoantibodies against dsDNA, chromatin, Sm, SmRNP and RNP A (p<0.01). Patient and unrelated control sera reacted to the highly repetitive glycine and alanine domain of EBNA-1. An epitope spanning EBNA-1410-420 was identified in sera of patients with SLE and showed limited binding by FDR and control sera. Filipino patients with SLE have elevated prevalence and concentrations of antibodies against EBV, CMV, HSV-1 and HSV-2 antigens, along with altered anti-EBNA-1 specificities. EBV reactivation is more common among Filipino patients with SLE compared with healthy Filipinos and may contribute to SLE pathogenesis in this population.