Identification of a HERV-K env surface peptide highly recognized in Rheumatoid Arthritis (RA) patients: a cross-sectional case-control study
Identification of a HERV-K env surface peptide highly recognized in Rheumatoid Arthritis (RA) patients: a cross-sectional case-control study
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DOI：
10.1111/cei.12964
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发表时间：
2017-07-01
影响因子：
4.6
通讯作者：
Sechi, L. A.
中科院分区：
文献类型：
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作者：
Mameli, G.;Erre, G. L.;Sechi, L. A.
内源性逆转录病毒(HERV)被认为是几种自身免疫性疾病的致病因素。其中，Herv-K病毒最近被报道与类风湿关节炎(RA)的发病有关。在这项研究中，我们探讨了针对Herv-K的体液免疫反应作为RA的潜在致病机制的作用。通过生物信息学分析，从HERV-K包膜蛋白胞外部分筛选出4个不同的多肽(env-su(19-37)、env-su(109-126)、env-su(164-186)、env-su(209-226))。然后用间接酶联免疫吸附试验(ELISA)对70例RA患者和71例健康对照(HC)的血液样本进行抗体定量。使用Mann-Whitney检验分析两组之间的差异。通过双变量回归分析探讨类风湿关节炎实验室、临床指标和免疫球蛋白G水平之间的潜在相关性。血清抗HERV-K四个多肽之一的自身抗体(env-su(19-37))在RA组显著高于HC组(19%比3%，P=00025)。亚组分析显示，抗Herv-K多肽体液反应与临床、血清学和临床RA疾病描述指标之间没有关联。与一般人群相比，本组RA患者血清对Herv-K env-su(19-37)肽有明显的反应，提示Herv-K相关的二次抗原驱动的免疫反应在RA的发病机制中起作用。需要进一步的研究来证实这些结果，并探索这种HERV-K表面多肽作为潜在治疗靶点的作用。
Endogenous retroviruses (HERV) are believed to be pathogenic in several autoimmune diseases. Among them, HERV-K viruses have been reported recently to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study we have explored the role of humoral immune response against HERV-K as a potential pathogenetic mechanism in RA. Four different peptides from the extracellular portion of the env protein of HERV-K (env-su(19-37), env-su(109-126), env-su(164-186), env-su(209-226)) were selected by bioinformatic analysis on the basis of their putative immunogenicity. Indirect enzyme-linked immunosorbent assay (ELISA) was then carried out to quantify antibodies against those peptides on blood samples of 70 consecutive RA patients and 71 healthy controls (HC). Differences between the two groups were analysed using the Mann-Whitney test. Potential correlations between RA laboratory, clinical descriptors and immunoglobulin (Ig)G levels were explored by bivariate regression analysis. Serum autoantibodies against one of four tested peptides of HERV-K (env-su(19-37)) were significantly higher in RA than in HC (19 versus 3%, P=00025). Subgroup analysis showed no association between anti-HERV-K peptide humoral response and clinical, serological and clinimetric RA disease descriptors. Serum from RA patients in our series reacted significantly against HERV-K env-su(19-37) peptide in comparison to the general population suggesting a role for the HERV-K- related, secondary antigenic-driven immune response in the pathogenesis of RA. Further studies are needed to confirm these results and to explore the role of this HERV-K surface peptide as a potential therapeutic target.