PDF(Pubmed)
Abstract：
UNASSIGNED: Galactose-deficient IgA1 (GdIgA1) is critical in the formation of immunodeposits in IgA nephropathy (IgAN), whereas the origin of GdIgA1 is unknown. We focused on the immune response to fecal microbiota in patients with IgAN.
UNASSIGNED: By running 16S ribosomal RNA gene sequencing, we compared IgAN samples to the control samples from household-matched or non-related individuals. Levels of plasma GdIgA1 and poly-IgA complexes were measured, and candidate microbes that can either incite IgA-directed antibody response or degrade IgA through specific IgA protease activities were identified.
UNASSIGNED: The IgAN group showed a distinct composition of fecal microbiota as compared to healthy controls. Particularly, high abundance of Escherichia-Shigella was associated with the disease group based on analyses using receiver operating characteristic (area under curve, 0.837; 95% CI, 0.738-0.914), principle coordinates, and the linear discriminant analysis effect size algorithm (linear discriminant analysis score, 4.56; p < 0.001). Accordingly, the bacterial levels directly correlated with high titers of plasma GdIgA1(r = 0.36, p < 0.001), and patients had higher IgA1 against stx2(2.88 ± 0.46 IU/mL vs. 1.34 ± 0.35 IU/mL, p = 0.03), the main antigen of Escherichia-Shigella. Conversely, the healthy controls showed relatively higher abundance of the commensal bacteria that produce IgA-degrading proteases. Particularly, the abundance of some intestinal bacteria expressing IgA proteases showed an inverse correlation with the levels of plasma GdIgA1 in IgAN.
UNASSIGNED: Our data suggest that mucosal IgA production, including those of GdIgA1, is potentially linked to the humoral response to gut Escherichia-Shigella as one of the sources of plasma GdIgA1. Conversely, the IgA protease-producing microbiota in the gut are suppressed in patients with IgAN.
UNASSIGNED: By running 16S ribosomal RNA gene sequencing, we compared IgAN samples to the control samples from household-matched or non-related individuals. Levels of plasma GdIgA1 and poly-IgA complexes were measured, and candidate microbes that can either incite IgA-directed antibody response or degrade IgA through specific IgA protease activities were identified.
UNASSIGNED: The IgAN group showed a distinct composition of fecal microbiota as compared to healthy controls. Particularly, high abundance of Escherichia-Shigella was associated with the disease group based on analyses using receiver operating characteristic (area under curve, 0.837; 95% CI, 0.738-0.914), principle coordinates, and the linear discriminant analysis effect size algorithm (linear discriminant analysis score, 4.56; p < 0.001). Accordingly, the bacterial levels directly correlated with high titers of plasma GdIgA1(r = 0.36, p < 0.001), and patients had higher IgA1 against stx2(2.88 ± 0.46 IU/mL vs. 1.34 ± 0.35 IU/mL, p = 0.03), the main antigen of Escherichia-Shigella. Conversely, the healthy controls showed relatively higher abundance of the commensal bacteria that produce IgA-degrading proteases. Particularly, the abundance of some intestinal bacteria expressing IgA proteases showed an inverse correlation with the levels of plasma GdIgA1 in IgAN.
UNASSIGNED: Our data suggest that mucosal IgA production, including those of GdIgA1, is potentially linked to the humoral response to gut Escherichia-Shigella as one of the sources of plasma GdIgA1. Conversely, the IgA protease-producing microbiota in the gut are suppressed in patients with IgAN.
摘要：
■半乳糖缺陷型IgA1（GdIgA1）在IgA肾病（IgAN）的免疫沉积形成中至关重要，而GdIgA1的起源未知。我们关注IgAN患者对粪便微生物群的免疫反应。
■通过运行16S核糖体RNA基因测序，我们将IgAN样本与家庭匹配或非相关个体的对照样本进行了比较.测量血浆GdIgA1和聚IgA复合物的水平，和候选微生物可以激发IgA指导的抗体反应或通过特异性IgA蛋白酶活性降解IgA。
与健康对照相比,IgAN组显示出不同的粪便微生物群组成。特别是,根据使用受试者工作特征的分析，高丰度的大肠杆菌-志贺氏菌与疾病组相关(曲线下面积，0.837；95%CI，0.738-0.914），主坐标,和线性判别分析效果大小算法(线性判别分析得分，4.56；p<0.001）。因此，细菌水平与血浆GdIgA1的高滴度直接相关（r=0.36，p<0.001），并且患者的IgA1高于stx2（2.88±0.46IU/mLvs.1.34±0.35IU/mL，p=0.03),大肠杆菌志贺氏菌的主要抗原。相反，健康对照显示产生IgA降解蛋白酶的共生细菌的丰度相对较高。特别是,一些表达IgA蛋白酶的肠道细菌的丰度与IgAN中血浆GdIgA1的水平呈负相关。
■我们的数据表明粘膜IgA的产生，包括GdIgA1在内，可能与作为血浆GdIgA1来源之一的肠埃希氏菌-志贺氏菌的体液反应有关。相反，IgAN患者肠道中产生IgA蛋白酶的微生物群受到抑制。
■通过运行16S核糖体RNA基因测序，我们将IgAN样本与家庭匹配或非相关个体的对照样本进行了比较.测量血浆GdIgA1和聚IgA复合物的水平，和候选微生物可以激发IgA指导的抗体反应或通过特异性IgA蛋白酶活性降解IgA。
与健康对照相比,IgAN组显示出不同的粪便微生物群组成。特别是,根据使用受试者工作特征的分析，高丰度的大肠杆菌-志贺氏菌与疾病组相关(曲线下面积，0.837；95%CI，0.738-0.914），主坐标,和线性判别分析效果大小算法(线性判别分析得分，4.56；p<0.001）。因此，细菌水平与血浆GdIgA1的高滴度直接相关（r=0.36，p<0.001），并且患者的IgA1高于stx2（2.88±0.46IU/mLvs.1.34±0.35IU/mL，p=0.03),大肠杆菌志贺氏菌的主要抗原。相反，健康对照显示产生IgA降解蛋白酶的共生细菌的丰度相对较高。特别是,一些表达IgA蛋白酶的肠道细菌的丰度与IgAN中血浆GdIgA1的水平呈负相关。
■我们的数据表明粘膜IgA的产生，包括GdIgA1在内，可能与作为血浆GdIgA1来源之一的肠埃希氏菌-志贺氏菌的体液反应有关。相反，IgAN患者肠道中产生IgA蛋白酶的微生物群受到抑制。
