The Intrathecal Antibody Response in Multiple Sclerosis Brain Does Not React Against Measles Virus

Deandra L Walker, Mark P Burgoon
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Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) and is the most common disabling neurological disease of young adults. Although the cause of MS is unknown, genetic and epidemiological studies indicate that MS may be triggered by an environmental agent. The presence of intrathecally produced antibodies, which produce oligoclonal Ig bands in the CNS of MS patients, provides tools for investigating the target of the inflammatory response. In most of the CNS conditions with oligoclonal bands the target is known and the antibody is directed against an infectious, causative agent. For example, in subacute sclerosing panencephalitis, a measles virus (MV) infection of the brain, the oligoclonal bands and intrathecal antibodies are primarily directed against MV. In earlier studies of MS, we demonstrated that the intrathecal antibody response in MS brain does not react to varicella zoster or Epstein-Barr virus. The current study investigates the reactivity of the intrathecal antibody response in MS brain to MV. We isolated individual CD38(+) plasma cells from MS brain to produce recombinant antibodies (rAbs). These rAbs likely represent oligoclonal bands and were used to immunostain MV-infected or uninfected monkey kidney (Vero) cells. Although many of the rAbs from MS brain reacted against auto-antigens in several mouse and human tissues, none of fifteen MS rAbs reacted against MV-infected cells. These results indicate that measles virus is not a disease-relevant antigen in MS.

多发性硬化症脑鞘内抗体反应对麻疹病毒没有反应
多发性硬化症(MS)是一种中枢神经系统(CNS)的慢性炎症性脱髓鞘疾病,是年轻人最常见的致残神经系统疾病。虽然MS的病因尚不清楚,但遗传学和流行病学研究表明,MS可能是由环境因素引发的。鞘内产生的抗体在MS患者的中枢神经系统中产生寡克隆Ig带,为研究炎症反应的目标提供了工具。在大多数具有寡克隆带的中枢神经系统条件下,目标是已知的,抗体是针对传染性病原体的。例如,在亚急性硬化性全脑炎(一种脑麻疹病毒感染)中,寡克隆带和鞘内抗体主要针对麻疹病毒。在MS的早期研究中,我们证明MS脑鞘内抗体反应对水痘带状疱疹或爱泼斯坦-巴尔病毒没有反应。本研究探讨MS脑鞘内抗体对MV的反应性。我们从MS脑中分离出单个CD38(+)浆细胞来产生重组抗体(rAbs)。这些rAbs可能代表寡克隆带,并用于对mv感染或未感染的猴肾(Vero)细胞进行免疫染色。尽管来自多发性硬化症大脑的许多rAbs对几种小鼠和人类组织中的自身抗原起反应,但15种MS rAbs中没有一种对感染mv的细胞起反应。这些结果表明麻疹病毒在多发性硬化症中不是疾病相关抗原。
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