空军军医大学学报2025，Vol.46Issue(11)：1539-1546,8.DOI:10.13276/j.issn.2097-1656.2025.11.019
人细小病毒B19通过Toll样受体促进胸腺增生相关重症肌无力的免疫机制:基于蛋白组学的整合分析
Immunological mechanism of human parvovirus B19 promoting thymic hyperplasia-related myasthenia gravis through Toll-like receptors:an integrated analysis based on proteomics
摘要
Abstract
Objective To preliminarily investigate whether human parvovirus B19(B19V)promotes the immune mechanism of thymic hyperplasia-associated myasthenia gravis(MG)via the Toll-like receptors(TLRs)signaling pathway based on proteomics and qRT-PCR,thereby providing clues for subsequent mechanistic research.Methods Twenty-six paraffin-embedded thymic hyperplasia tissues from our previous study,which had undergone nested PCR detection(including 14 with MG and 12 without MG),were selected for proteomic analysis.The samples were divided into three groups:MG with B19V DNA-positive(MG-B19-P)group,MG with B19V DNA-negative(MG-B19-N)group,and non-MG but B19V DNA-positive(N-MG-B19-P)group as control.Differentially expressed proteins(DEPs)between the MG-B19-P group and each of the other two groups were analyzed respectively,and relevant signaling pathways were screened using KEGG enrichment analysis.Furthermore,42 paraffin-embedded thymic hyperplasia tissues were selected and divided into H-B19-P group,H-B19-N group,H-GC group,and H-N-GC group based on B19V DNA amplification results and the presence or absence of germinal center(GC).The mRNA expression levels of molecules related to the TLRs pathway were detected by qRT-PCR to compare differences among groups.Results Proteomic analysis revealed that DEPs were present in the MG-B19-P group and both the MG-B19-N group and the N-MG-B19-P group,with significant enrichment in the TLRs signaling pathway.qRT-PCR results showed that the TLR3 mRNA expression level was significantly higher in the H-B19-P group than in the H-B19-N group(P＜0.05).Similarly,the TLR9 mRNA expression level was significantly higher in the H-GC group than in the H-N-GC group(P＜0.01).However,no significant differences in TLR7 expression were observed among all groups.Conclusion B19V may promote the development of MG by modulating the expression of TLR3 and TLR9 and participating in the immune response of thymic hyperplasia at different stages.This study provides new insights for elucidating the immune mechanism of B19V in MG associated with thymic abnormalities and suggests TLR3 and TLR9 as potential therapeutic targets.关键词
人细小病毒B19/胸腺增生/重症肌无力/蛋白组学/Toll样受体/KEGG分析/生发中心/自身免疫性疾病Key words
human parvovirus B19/thymic hyperplasia/myasthenia gravis/proteomics/Toll-like receptor/KEGG analysis/germinal center/autoimmune disease分类
医药卫生引用本文复制引用
张燕,田静,马娇,封兰兰,王圆圆,张富琴,梁佳敏,巩丽..人细小病毒B19通过Toll样受体促进胸腺增生相关重症肌无力的免疫机制:基于蛋白组学的整合分析[J].空军军医大学学报,2025,46(11):1539-1546,8.基金项目
国家自然科学基金(82472279) （82472279）
