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特应性皮炎患者中潜伏性巨细胞病毒(CMV)感染的亚临床激活及抗CMV免疫反应

Subclinical activation of latent cytomegalovirus (CMV) infection and anti-CMV immune response in patients with atopic dermatitis.

作者信息

Döcke W-D, Kiessling C, Worm M, Friedrich M, Pruss A, Weitz M, Prösch S, Kern F, Volk H-D, Sterry W, Asadullah K

机构信息

Institute of Medical Immunology, Department of Dermatology, University Hospital Charité, Berlin Humboldt University, D-10098 Berlin, Germany.

出版信息

Br J Dermatol. 2003 May;148(5):954-63. doi: 10.1046/j.1365-2133.2003.05263.x.

Abstract

BACKGROUND

Microbiological infections are considered to be of pathophysiological importance in atopic dermatitis (AD). As yet, no information is available regarding cytomegalovirus (CMV) infection in this disease. This, however, is of interest because of the high prevalence of latent infections in the general population, the frequent reactivation in inflammatory diseases, and the immunomodulating capacity of CMV.

OBJECTIVES

To investigate the prevalence of latent CMV infection, the frequency of active CMV infection, and the immune response to CMV in patients with moderate to severe AD. Methods To detect active infection we analysed CMV antigen expression by peripheral blood mononuclear cells (PBMC) from 27 patients with moderate to severe AD in comparison with 53 healthy volunteers. We used three monoclonal antibodies recognizing different CMV-encoded antigens and immunocytological staining (alkaline phosphatase-antialkaline phosphatase technique).

RESULTS

Patients with AD had a higher mean frequency of CMV-positive PBMC: 2.25 per 10 000 vs. 0.74 per 10 000 in controls (P = 0.001) as well as a higher incidence of CMV antigenaemia: 29.6% vs. 7.5% (P < 0.01). Seropositivity for anti-CMV IgG antibodies indicated subclinical activation of latent infection. Remarkably, a clearance of CMV antigenaemia was observed during anti-eczematous treatment. Significantly higher plasma levels of tumour necrosis factor-alpha, which is involved in CMV reactivation, and interleukin-12, which is crucial for an antiviral cellular immune response, were observed in AD patients in comparison with healthy volunteers. Furthermore, a significantly enhanced frequency of circulating activated HLA-DR+ T cells especially in CMV-seropositive AD patients (19.3% vs. 13.5% in seronegative AD patients vs. 10.2% in controls) suggested that the active CMV infection triggers a cellular immune response. This was also supported by a high frequency of CMV-specific interferon-gamma-producing T cells in CMV-seropositive patients with AD.

CONCLUSIONS

Our data suggest that active, subclinical CMV infection is more frequent in patients with moderate to severe AD and may have immunopathophysiological relevance.

摘要

背景

微生物感染被认为在特应性皮炎(AD)中具有病理生理学重要性。然而,关于该疾病中巨细胞病毒(CMV)感染的信息尚无报道。鉴于CMV在普通人群中潜伏感染的高患病率、在炎症性疾病中的频繁再激活以及其免疫调节能力,这一点颇具研究意义。

目的

研究中度至重度AD患者中潜伏CMV感染的患病率、活动性CMV感染的频率以及对CMV的免疫反应。方法:为检测活动性感染,我们分析了27例中度至重度AD患者外周血单个核细胞(PBMC)中的CMV抗原表达,并与53名健康志愿者进行比较。我们使用了三种识别不同CMV编码抗原的单克隆抗体及免疫细胞化学染色(碱性磷酸酶 - 抗碱性磷酸酶技术)。

结果

AD患者中CMV阳性PBMC的平均频率更高:每10000个细胞中为2.25个,而对照组为每10000个细胞中0.74个(P = 0.001),CMV抗原血症的发生率也更高:分别为29.6%和7.5%(P < 0.01)。抗CMV IgG抗体血清阳性表明潜伏感染的亚临床激活。值得注意的是,在抗湿疹治疗期间观察到CMV抗原血症的清除。与健康志愿者相比,AD患者中参与CMV再激活的肿瘤坏死因子 - α以及对抗病毒细胞免疫反应至关重要的白细胞介素 - 12的血浆水平显著更高。此外,循环活化的HLA - DR + T细胞频率显著增加,尤其是在CMV血清阳性的AD患者中(血清阴性AD患者为19.3%,血清阳性AD患者为13.5%,对照组为10.2%),这表明活动性CMV感染引发了细胞免疫反应。CMV血清阳性的AD患者中CMV特异性产生干扰素 - γ的T细胞的高频率也支持了这一点。

结论

我们的数据表明,中度至重度AD患者中活动性、亚临床CMV感染更为常见,且可能具有免疫病理生理学相关性。

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