Perron Hervé, Mekaoui Lila, Bernard Corinne, Veas Francisco, Stefas Ilias, Leboyer Marion
Geneuro, Plan-Les-Ouates, Geneva, Switzerland.
Biol Psychiatry. 2008 Dec 15;64(12):1019-23. doi: 10.1016/j.biopsych.2008.06.028. Epub 2008 Aug 29.
Recent and independent molecular studies have shown an association between human endogenous retroviruses type "W" family (HERV-W) and schizophrenia, mostly by polymerase chain reaction studies, but none has yet addressed specific antigen detection in living patients.
Forty-nine schizophrenic patients and an equivalent number of healthy control subjects were included in the present exploratory study. The HERV-W GAG and envelope (ENV) proteins were quantified in the serum with a dedicated immunoassay set-up with specific monoclonal antibodies to either antigen.
In schizophrenic patients, positive antigenemia for ENV was found in 23 of 49 (47%) and for GAG in 24 of 49 (49%). Only 1 of 30 (3%) for ENV and 2 of 49 (4%) for GAG were positive in blood donors (p < .01 for ENV; p < .001 for GAG). Interestingly, bioclinical data analyses revealed significant correlation between GAG or ENV antigenemia (a protein causing dysimmune inflammatory effects) and C-reactive protein (CRP) levels (a systemic inflammation biomarker).
Frequently elevated CRP has previously been described in schizophrenic patients and has been shown to match with an evolution toward cognitive deficit and neuronal loss. Elsewhere viruses such as influenza, long-associated with risk for schizophrenia through perinatal infections, have been shown to activate HERV-W elements in human cells. We therefore discuss a relationship between environment factors long-associated with early risk, genetic factors represented by this endogenous family, the production of its pro-inflammatory ENV protein and known "inflammation-mediated" neurotoxicity, as a possible hypothesis for a pathogenic cascade in association with HERV-W. Our present results thus confirm that HERV-W studies have opened a novel avenue of research in schizophrenia.
近期独立的分子研究表明，人类内源性逆转录病毒W家族（HERV-W）与精神分裂症之间存在关联，主要通过聚合酶链反应研究，但尚未有研究涉及对活体患者进行特异性抗原检测。
本探索性研究纳入了49例精神分裂症患者和数量相当的健康对照者。使用针对每种抗原的特异性单克隆抗体的专用免疫分析方法，对血清中的HERV-W GAG和包膜（ENV）蛋白进行定量。
在精神分裂症患者中，49例中有23例（47%）ENV抗原血症呈阳性，49例中有24例（49%）GAG抗原血症呈阳性。献血者中ENV为30例中的1例（3%）呈阳性，GAG为49例中的2例（4%）呈阳性（ENV，p <.01；GAG，p <.001）。有趣的是，生物临床数据分析显示，GAG或ENV抗原血症（一种引起免疫失调炎症效应的蛋白质）与C反应蛋白（CRP）水平（一种全身炎症生物标志物）之间存在显著相关性。
先前已描述精神分裂症患者中CRP经常升高，并已证明其与认知缺陷和神经元丢失的进展相匹配。在其他地方，诸如流感等长期以来通过围产期感染与精神分裂症风险相关的病毒，已被证明可激活人类细胞中的HERV-W元件。因此，我们讨论了长期与早期风险相关的环境因素、以这个内源性家族为代表的遗传因素、其促炎ENV蛋白的产生以及已知的“炎症介导”神经毒性之间的关系，作为与HERV-W相关的致病级联反应的一种可能假设。我们目前的结果因此证实，HERV-W研究为精神分裂症开辟了一条新的研究途径。
