Anti-cytokine autoantibodies in postherpetic neuralgia.
Anti-cytokine autoantibodies in postherpetic neuralgia.
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DOI：
10.1186/s12967-015-0695-6
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发表时间：
2015-10-20
影响因子：
7.4
通讯作者：
Iadarola MJ
中科院分区：
文献类型：
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作者：
Bayat A;Burbelo PD;Browne SK;Quinlivan M;Martinez B;Holland SM;Buvanendran A;Kroin JS;Mannes AJ;Breuer J;Cohen JI;Iadarola MJ
水痘带状疱疹病毒（VZV）激活引起带状疱疹后神经痛（PHN）的机制尚未完全阐明。基于以前的研究，确定了抗细胞因子自身抗体在机会性感染患者中的致病作用，我们探讨了PHN的这种可能性。带状疱疹（HZ）患者的血清没有和PHN（N = 115和83，分别）进行了检查，针对多种细胞因子和其他已知的自身抗原的自身抗体的存在。此外，对一组患有复杂性局部疼痛综合征或神经性疼痛的患者进行了针对选定细胞因子的自身抗体测试。还测量了HZ和PHN患者中针对VZV、爱泼斯坦巴尔病毒和单纯疱疹病毒-2的抗体水平。对具有高水平抗细胞因子自身抗体的患者血清进行体外中和活性的功能测试。6例PHN受试者表现出抗干扰素-α、干扰素-γ、GM-CSF或白细胞介素-6的单一自身抗体水平显著升高。相比之下，HZ和疼痛对照组分别显示出针对这四种细胞因子的低或无自身抗体。进一步的分析显示，一个PHN患者与高水平的抗白细胞介素-6自身抗体有一个显着降低抗体水平VZV，可能反映了不良的T细胞免疫VZV。体外功能检测显示，5例抗细胞因子自身抗体阳性PHN受试者中有3例存在针对干扰素-α、GM-CSF或白细胞介素-6的中和性自身抗体。相反，没有PHN的HZ患者没有中和自身抗体。这些结果表明，在某些受试者中散发的抗细胞因子自身抗体可能会导致自身免疫性免疫缺陷综合征，导致不受控制的VZV再激活，神经损伤和随后的PHN。
The mechanisms by which varicella zoster virus (VZV) reactivation causes postherpetic neuralgia (PHN), a debilitating chronic pain condition, have not been fully elucidated. Based on previous studies identifying a causative role for anti-cytokine autoantibodies in patients with opportunistic infections, we explored this possibility in PHN. Sera from herpes zoster (HZ) patients without and with PHN (N = 115 and 83, respectively) were examined for the presence of autoantibodies against multiple cytokines, and other known autoantigens. In addition, a cohort of patients with complex regional pain syndrome or neuropathic pain was tested for autoantibodies against selected cytokines. Antibody levels against VZV, Epstein Barr virus, and herpes simplex virus-2 were also measured in the HZ and PHN patients. Patient sera with high levels of anti-cytokine autoantibodies were functionally tested for in vitro neutralizing activity. Six PHN subjects demonstrated markedly elevated levels of single, autoantibodies against interferon-α, interferon-γ, GM-CSF, or interleukin-6. In contrast, the HZ and the pain control group showed low or no autoantibodies, respectively, against these four cytokines. Further analysis revealed that one PHN patient with high levels of anti-interleukin-6 autoantibodies had a markedly depressed antibody level to VZV, potentially reflecting poor T cell immunity against VZV. In vitro functional testing revealed that three of the five anti-cytokine autoantibody positive PHN subjects had neutralizing autoantibodies against interferon-α, GM-CSF or interleukin-6. In contrast, none of the HZ patients without PHN had neutralizing autoantibodies. These results suggest the possibility that sporadic anti-cytokine autoantibodies in some subjects may cause an autoimmune immunodeficiency syndrome leading to uncontrolled VZV reactivation, nerve damage and subsequent PHN.