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系统性红斑狼疮合并扩张型心肌病患者中与Th17相关的细胞因子:与细小病毒B19感染的可能联系

Th17-related cytokines in systemic lupus erythematosus patients with dilated cardiomyopathies: a possible linkage to parvovirus B19 infection.

作者信息

Chen Der-Yuan, Chen Yi-Ming, Tzang Bor-Show, Lan Joung-Liang, Hsu Tsai-Ching

机构信息

Division of Allergy, Immunology and Rheumatology, Department of Medical Education, Taichung Veterans General Hospital, Taichung City, Taiwan; Faculty of Medicine, National Yang Ming University, Taipei, Taiwan; Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan; Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.

Division of Allergy, Immunology and Rheumatology, Department of Medical Education, Taichung Veterans General Hospital, Taichung City, Taiwan; Faculty of Medicine, National Yang Ming University, Taipei, Taiwan; Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.

出版信息

PLoS One. 2014 Dec 2;9(12):e113889. doi: 10.1371/journal.pone.0113889. eCollection 2014.

Abstract

Dilated cardiomyopathies (DCM) are a major cause of mortality in patients with systemic lupus erythematosus (SLE). Immune responses induced by human parvovirus B19 (B19) are considered an important pathogenic mechanism in myocarditis or DCM. However, little is known about Th17-related cytokines in SLE patients with DCM about the linkage with B19 infection. IgM and IgG against B19 viral protein, and serum levels of Th17-related cytokines were determined using ELISA in eight SLE patients with DCM and six patients with valvular heart disease (VHD). Humoral responses of anti-B19-VP1u and anti-B19-NS1 antibody were assessed using Western blot and B19 DNA was detected by nested Polymerase Chain Reaction (PCR). Levels of interleukin (IL)-17, IL-6, IL-1β, and tumor necrosis factor (TNF)-α were significantly higher in SLE patients with DCM (mean ± SEM, 390.99±125.48 pg/ml, 370.24±114.09 pg/ml, 36.01±16.90 pg/ml, and 183.84±82.94 pg/ml, respectively) compared to healthy controls (51.32±3.04 pg/ml, p<0.001; 36.88±6.64 pg/ml, p<0.001; 5.39±0.62 pg/ml, p<0.005; and 82.13±2.42 pg/ml, p<0.005, respectively). Levels of IL-17 and IL-6 were higher in SLE patients with DCM versus those with VHD (both p<0.01). Five (62.5%) of DCM patients had detectable anti-B19-NS1 IgG and four (50.0%) of them had anti-B19-VP1u IgG, whereas only one (16.7%) of VHD patients had detectable anti-B19-NS1 IgG and anti-B19-VP1u IgG. Serum levels of IL-17, IL-6 and IL-1β were markedly higher in SLE patients with anti-B19-VP1u IgG and anti-B19-NS1 IgG compared to those without anti-B19-VP1u IgG or anti-B19-NS1 IgG, respectively. These suggest a potential association of B19 with DCM and Th17-related cytokines implicated in the pathogenesis of DCM in SLE patients.

摘要

扩张型心肌病(DCM)是系统性红斑狼疮(SLE)患者死亡的主要原因。人细小病毒B19(B19)诱导的免疫反应被认为是心肌炎或DCM的重要致病机制。然而,关于合并DCM的SLE患者中与Th17相关的细胞因子及其与B19感染的联系,人们知之甚少。采用酶联免疫吸附测定(ELISA)法检测了8例合并DCM的SLE患者和6例瓣膜性心脏病(VHD)患者的抗B19病毒蛋白IgM和IgG以及与Th17相关的细胞因子血清水平。采用蛋白质印迹法评估抗B19-VP1u和抗B19-NS1抗体的体液反应,采用巢式聚合酶链反应(PCR)检测B19 DNA。合并DCM的SLE患者白细胞介素(IL)-17、IL-6、IL-1β和肿瘤坏死因子(TNF)-α水平显著高于健康对照(分别为均值±标准误,390.99±125.48 pg/ml、370.24±114.09 pg/ml、36.01±16.90 pg/ml和183.84±82.94 pg/ml)(分别为51.32±3.04 pg/ml,p<0.001;36.88±6.64 pg/ml,p<0.001;5.39±0.62 pg/ml,p<0.005;82.13±2.42 pg/ml,p<0.005)。合并DCM的SLE患者IL-17和IL-6水平高于VHD患者(均p<0.01)。5例(62.5%)DCM患者可检测到抗B19-NS1 IgG,4例(50.0%)可检测到抗B19-VP1u IgG,而VHD患者中只有1例(16.7%)可检测到抗B19-NS1 IgG和抗B19-VP1u IgG。与未检测到抗B19-VP1u IgG或抗B19-NS1 IgG的SLE患者相比,检测到抗B19-VP1u IgG和抗B19-NS1 IgG的SLE患者血清IL-17、IL-6和IL-1β水平明显更高。这些结果提示B19与DCM之间可能存在关联,且Th17相关细胞因子与SLE患者DCM的发病机制有关。

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