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肠道微生物群和炎性细胞因子的差异促成了免疫球蛋白A血管炎。

Differential gut microbiota and inflammatory cytokines contribute to IgA vasculitis.

作者信息

Chen Yi, Zeng Yugui, Zhang Yuanzhen, Chen Junyan, Qian Yifang, Huang Jun, Chen Guangming, Xia Guizhi, Wang Chengfeng, Feng Ai, Nie Xiaojing

机构信息

Department of Paediatrics, Fuzong Clinical Medical College of Fujian Medical University, Fuzhou; and Department of Paediatrics, 900th Hospital of PLA Joint Logistic Support Force, Fuzhou, China.

Department of Paediatrics, 900th Hospital of PLA Joint Logistic Support Force, Fuzhou; and Department of Paediatrics, Dongfang Hospital of Xiamen University, School of Medicine, Xiamen University, Fuzhou, China.

出版信息

Clin Exp Rheumatol. 2025 Apr;43(4):563-574. doi: 10.55563/clinexprheumatol/ff61t7. Epub 2025 Apr 8.

DOI:10.55563/clinexprheumatol/ff61t7
PMID:40201970
Abstract

OBJECTIVES

Immunoglobulin A vasculitis (IgAV) is the most common form of vasculitis in childhood. Emerging evidence indicates that gut microbiota plays a key role in the pathogenesis of IgAV. However, the factors linking gut microbiota to the onset and progression of IgAV are poorly understood. We aimed to demonstrate that the presence of a specific dysbiosis in patients with IgAV contributes to the onset of IgAV.

METHODS

We transplanted gut microbiota from human donors with IgAV or healthy controls (HCs). The changes in gut microbiota and serum indexes of the recipient mice were detected, and the IgAV-associated bacteria were determined by integrating the results from the mouse sequence data analysis with the human sequence results.

RESULTS

55 amplicon sequence variants (ASVs) specific to IgAV children were detected in the recipient IgAV microbiota (rIMb) mice, and 35 ASVs specific to healthy children were detected in the recipient healthy microbiota (rHMb) mice. Gut microbiota in rIMb mice differs from that in rHMb mice. Alcaligenaceae could discriminate rIMb from rHMb mice, while its abundance was decreased in rIMb compared to rHMb (p<0.05). In children with IgAV, the abundance of Burkholderiaceae (Alcaligenaceae accounted for 99.7%) at the family level was significantly lower compared to HCs, which can be used to distinguish children with IgAV from HCs, and the constructed receiver operating characteristic (ROC) curve had an area under the curve (AUC) value of 0.766. In addition, the rIMb group had a markedly higher interleukin (IL)-17A and IL-21 level than those in the rHMb group. The Spearman correlation analysis indicated significant correlations between the relative levels of these pro-inflammatory cytokines, IgA and alterations of gut microbiota.

CONCLUSIONS

IgAV is characterised by disturbances of gut microbiota composition and an imbalance in inflammatory cytokines. The manipulation of gut microbiota could be a possible way to prevent and manage IgAV.

摘要

目的

免疫球蛋白A血管炎(IgAV)是儿童期最常见的血管炎形式。新出现的证据表明,肠道微生物群在IgAV的发病机制中起关键作用。然而,将肠道微生物群与IgAV的发生和发展联系起来的因素尚不清楚。我们旨在证明IgAV患者中特定的微生物失调与IgAV的发病有关。

方法

我们移植了来自IgAV人类供体或健康对照(HCs)的肠道微生物群。检测受体小鼠肠道微生物群和血清指标的变化,并通过将小鼠序列数据分析结果与人类序列结果相结合来确定与IgAV相关的细菌。

结果

在受体IgAV微生物群(rIMb)小鼠中检测到55个IgAV儿童特有的扩增子序列变异(ASV),在受体健康微生物群(rHMb)小鼠中检测到35个健康儿童特有的ASV。rIMb小鼠的肠道微生物群与rHMb小鼠不同。产碱菌科可以区分rIMb和rHMb小鼠,但其在rIMb中的丰度比rHMb中降低(p<0.05)。在IgAV儿童中,伯克霍尔德菌科(产碱菌科占99.7%)在家族水平上的丰度显著低于HCs,可用于区分IgAV儿童和HCs,构建的受试者工作特征(ROC)曲线的曲线下面积(AUC)值为0.766。此外,rIMb组的白细胞介素(IL)-17A和IL-21水平明显高于rHMb组。Spearman相关性分析表明,这些促炎细胞因子、IgA的相对水平与肠道微生物群的改变之间存在显著相关性。

结论

IgAV的特征是肠道微生物群组成紊乱和炎性细胞因子失衡。操纵肠道微生物群可能是预防和管理IgAV的一种可行方法。

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