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分子模拟驱动蛛网膜下腔神经囊尾蚴病中局部产生的自身抗体。

Molecular Mimicry Drives Locally Produced Autoantibodies in Subarachnoid Neurocysticercosis.

作者信息

Guzmán Janitzio J, Bah Aissatou, Bennuru Sasisekhar, Harrison Sarah, Nash Theodore E, Sciurba Joshua, Thumm Lauren, Nutman Thomas B, O'Connell Elise M

机构信息

Helminth Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.

Clinical Parasitology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.

出版信息

Open Forum Infect Dis. 2025 May 8;12(5):ofaf276. doi: 10.1093/ofid/ofaf276. eCollection 2025 May.

Abstract

BACKGROUND

Subarachnoid neurocysticercosis (SANCC) is a condition manifested by chronic meningitis induced by infection with . We sought to determine if there is evidence of autoantibody production in SANCC and whether local production of autoantibodies could be driven by immunogenic homologues found in .

METHODS

Reactivity of pooled cerebral spinal fluid (CSF) from SANCC patients and uninfected controls was screened against a human proteome chip. Serum from 27 SANCC patients was then tested for antibodies to the 15 top screen hits using a Luciferase ImmunoPrecipitation System (LIPS). Eight human proteins were further tested using CSF from SANCC and controls. In parallel, homologues were expressed and screened using LIPS. Antibodies directed at the 2 proteins with significant reactivity were then used to probe crude antigen using a 2D immunoblot. Reactive proteins were subjected to mass spectroscopy for identification.

RESULTS

Significant immunoglobulin G reactivity was seen in the CSF of SANCC compared with uninfected controls to both human annexin A8 () and chromatin complexes subunit BAP18 () and their homologues on LIPS testing. 2D-separated soluble antigen was probed with either antihuman-ANXA8 or antihuman BAP18 antibodies in immunoblotting. The antihuman ANXA8 antibody identified annexin B3 (GenBank: AAY27744.1), whereas the antihuman BAP18 antibody identified cestode enzymes involved in metabolic pathways.

CONCLUSIONS

-derived annexin and metabolic enzymes contain epitopes that likely drive local CSF antibody production that cross-reacts with human and and may contribute to the pathology underlying SANCC.

摘要

背景

蛛网膜下腔神经囊尾蚴病(SANCC)是由 感染引起的慢性脑膜炎所表现出的一种病症。我们试图确定SANCC中是否存在自身抗体产生的证据,以及自身抗体的局部产生是否可由 在 中发现的免疫原性同源物驱动。

方法

使用人类蛋白质组芯片筛选SANCC患者和未感染对照的混合脑脊液(CSF)的反应性。然后使用荧光素酶免疫沉淀系统(LIPS)检测27例SANCC患者血清中针对15个顶级筛选命中蛋白的抗体。使用来自SANCC患者和对照的CSF进一步检测8种人类蛋白质。同时,表达并使用LIPS筛选 同源物。然后使用针对具有显著反应性的2种蛋白质的抗体,通过二维免疫印迹法探测 粗抗原。对反应性蛋白质进行质谱鉴定。

结果

与未感染对照相比,在LIPS检测中,SANCC患者的CSF中观察到针对人膜联蛋白A8( )和染色质复合体亚基BAP18( )及其 同源物的显著免疫球蛋白G反应性。在免疫印迹中,用抗人ANXA8或抗人BAP18抗体探测二维分离的 可溶性抗原。抗人ANXA8抗体鉴定出 膜联蛋白B3(GenBank:AAY27744.1),而抗人BAP18抗体鉴定出参与代谢途径的绦虫酶。

结论

来源的膜联蛋白和代谢酶含有可能驱动局部CSF抗体产生的表位,这些抗体与人 和 发生交叉反应,并可能导致SANCC的病理改变。

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