Virus-Triggered Autoimmunity Was Associated With Hirschsprung's Disease Through Activation of Innate Immunity.

IF 3.5 3区 医学 Q2 IMMUNOLOGY Journal of Immunology Research Pub Date : 2024-10-26 eCollection Date: 2024-01-01 DOI:10.1155/2024/4838514
Weiyong Zhong, Chaoting Lan, Yuqiong Chen, Kai Song, Zuyi Ma, Jixiao Zeng, Lihua Huang, Yan Zhang, Yun Zhu, Huimin Xia
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Abstract

Background: Hirschsprung's disease (HSCR) is a congenital enteric nervous system (ENS) disorder. Genetics cannot explain most sporadic cases. To explore the relationship between pathogen infection, autoantibodies, innate immune, and HSCR. Methods: Pathogen microarray was conducted in the serum of the prospective neonatal abdominal distension (NAD) cohort, consisting of 56 children followed for at least 6 months until the final diagnosis of HSCR was determined or excluded. We conducted an autoantibody microarray in an HSCR cohort, which is comprised of diagnosed HSCR patients (HSCR) and healthy control subjects (HC). RNA-seq of colon tissues from aganglionic and ganglionic segments of HSCR patients was performed. Results: Experimental results show that the serum lgM and lgG of enterovirus 71 (EV71) were significantly higher in HSCR than in the gastrointestinal dysfunction (GI) group, with a prediagnose value reaching area under the curve (AUC) over 0.76. We discovered that a group of autoantibodies were significantly higher in HSCR including neuronal pentraxin 1 (NPTX1), amyloid, neuron lysate, and myelin-associated oligodendrocytic basic protein (MOBP) than that in the HC group. These four autoantibodies could distinguish HSCR from the HC group, with a combined AUC of over 0.90 using both serum IgG and IgM. Further analysis showed that wide activation of innate immune pathways, including toll-like receptor (TLR) signaling pathway, neutrophil-to-lymphocyte ratio (NLR) signaling pathway, red cell distribution width to lymphocyte ratio (RLR) signaling pathway, and cyclic adenosine monophosphate (cAMP) signaling pathway in aganglionic compared to ganglionic segments of HSCR. Conclusion: This study suggested that virus-triggered autoimmunity may contribute to HSCR through activation of innate immunity, which facilitates the diagnosis and prevention of HSCR.

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病毒通过激活先天性免疫诱发自身免疫与赫氏肺病有关
背景:赫氏病(HSCR)是一种先天性肠神经系统(ENS)疾病。遗传无法解释大多数散发性病例。目的:探讨病原体感染、自身抗体、先天性免疫与 HSCR 之间的关系。方法在前瞻性新生儿腹胀(NAD)队列的血清中进行病原体微阵列分析,该队列由 56 名儿童组成,随访至少 6 个月,直至确定或排除 HSCR 的最终诊断。我们在 HSCR 队列中进行了自身抗体芯片分析,该队列由确诊的 HSCR 患者(HSCR)和健康对照组(HC)组成。我们还对 HSCR 患者的结肠神经节和神经节组织进行了 RNA 序列分析。结果显示实验结果表明,HSCR 患者血清中肠道病毒 71(EV71)的 lgM 和 lgG 明显高于胃肠功能紊乱(GI)组,预诊断值曲线下面积(AUC)超过 0.76。我们发现,HSCR患者的一组自身抗体明显高于HC组,包括神经元五肽1(NPTX1)、淀粉样蛋白、神经元裂解物和髓鞘相关少突胶质细胞碱性蛋白(MOBP)。这四种自身抗体可将 HSCR 与 HC 组区分开来,使用血清 IgG 和 IgM 的综合 AUC 超过 0.90。进一步的分析表明,与神经节段相比,HSCR 的神经节段先天性免疫通路被广泛激活,包括收费样受体(TLR)信号通路、中性粒细胞与淋巴细胞比值(NLR)信号通路、红细胞分布宽度与淋巴细胞比值(RLR)信号通路和环磷酸腺苷(cAMP)信号通路。结论本研究表明,病毒触发的自身免疫可能通过激活先天性免疫导致 HSCR,这有助于 HSCR 的诊断和预防。
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来源期刊
CiteScore
6.90
自引率
2.40%
发文量
423
审稿时长
15 weeks
期刊介绍: Journal of Immunology Research is a peer-reviewed, Open Access journal that provides a platform for scientists and clinicians working in different areas of immunology and therapy. The journal publishes research articles, review articles, as well as clinical studies related to classical immunology, molecular immunology, clinical immunology, cancer immunology, transplantation immunology, immune pathology, immunodeficiency, autoimmune diseases, immune disorders, and immunotherapy.
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