肠道微生物群失调和肠道屏障功能障碍通过增加Gd-IgA1的产生促进IgA肾病。

Gut Dysbiosis and Intestinal Barrier Dysfunction Promotes IgA Nephropathy by Increasing the Production of Gd-IgA1.

作者信息

Tang Yuyan, Zhu Yifan, He Haidong, Peng Yinshun, Hu Ping, Wu Jiajun, Sun Weiqian, Liu Ping, Xiao Yong, Xu Xudong, Wei Minggang

机构信息

Department of Traditional Chinese Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.

Department of Nephrology, Minhang Hospital, Fudan University, Shanghai, China.

出版信息

Front Med (Lausanne). 2022 Jul 7;9:944027. doi: 10.3389/fmed.2022.944027. eCollection 2022.

DOI:10.3389/fmed.2022.944027

PMID:35872757

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9302483/

Abstract

BACKGROUND

Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerular disease in adults worldwide. Several studies have reported that galactose-deficient IgA1 (Gd-IgA1) is involved in the pathogenesis of IgAN.

METHODS

Thirty-five patients with IgAN diagnosed with renal biopsy for the first time served as the experimental group, who were hospitalized in our department. Twenty normal healthy cases in the physical examination center of our hospital served as the control group. Then the levels of Gd-IgA1 in serum and urine, and intestinal mucosal barrier injury indexes [diamine oxidase (DAO), serum soluble intercellular adhesion molecule-1 (sICAM-1), D-lactate (D-LAC), and lipopolysaccharide (LPS)] and inflammatory factors [interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)] in the serum samples were detected. Fecal samples were collected to detect intestinal microbiota using 16 s rDNA sequencing. Then, we assessed possible correlations among clinical and laboratory findings.

RESULTS

In patients with IgAN, the levels of Gd-IgA1 both in the serum and urine were higher than that of the healthy control. Furthermore, urine Gd-IgA1 level was positively correlated with the serum creatinine level, 24 h urine protein, and M, S, and T parameters in the Oxford classification. ROC curve analysis showed that urine Gd-IgA1 has a greater diagnostic value (AUC = 0.9714, 95% CI, 0.932-1; < 0.0001) for IgAN. The best cutoff value for urine Gd-IgA1 was 0.745 ng·l/ml·μmol (sensitivity, 94%; specificity, 95%). The intestinal mucosal barrier damage indexes (DAO, sICAM-1, D-LAC, and LPS) were increased in the patients with IgAN, which were positively correlated with Gd-IgA1 levels ( < 0.05) both in serum and urine. The levels of inflammatory factors in the patients with IgAN were increased. 16 s rDNA analysis showed that the intestinal microbiota in these patients was disordered compared to that observed in the healthy subjects. were decreased and was increased in IgAN. The decreased populations of these flora were negatively and significantly correlated with urine Gd-IgA1 and the levels of DAO, sICAM-1, D-LAC, and LPS.

CONCLUSION

The urine Gd-IgA1 levels may be a non-invasive biological marker for evaluating kidney injury in IgAN. Gut flora dysbiosis and intestinal barrier dysfunction may be involved in Gd-IgA1 expression.

摘要

背景

免疫球蛋白A肾病（IgAN）是全球成年人中最常见的原发性肾小球疾病类型。多项研究报道，缺乏半乳糖的IgA1（Gd-IgA1）参与了IgAN的发病机制。

方法

35例首次经肾活检确诊为IgAN的患者作为实验组，在我科住院治疗。选取我院体检中心20例健康体检者作为对照组。然后检测血清和尿液中Gd-IgA1的水平，以及血清样本中的肠黏膜屏障损伤指标[二胺氧化酶（DAO）、血清可溶性细胞间黏附分子-1（sICAM-1）、D-乳酸（D-LAC）和脂多糖（LPS）]和炎症因子[白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）]。采集粪便样本，采用16 s rDNA测序检测肠道微生物群。然后，我们评估了临床和实验室检查结果之间可能存在的相关性。

结果

IgAN患者血清和尿液中Gd-IgA1水平均高于健康对照组。此外，尿Gd-IgA1水平与血清肌酐水平、24小时尿蛋白以及牛津分类中的M、S和T参数呈正相关。ROC曲线分析表明，尿Gd-IgA1对IgAN具有更大的诊断价值（AUC = 0.9714，95% CI，0.932 - 1；P < 0.0001）。尿Gd-IgA1的最佳截断值为0.745 ng·l/ml·μmol（敏感性为94%；特异性为95%）。IgAN患者的肠黏膜屏障损伤指标（DAO、sICAM-1、D-LAC和LPS）升高，且与血清和尿液中的Gd-IgA1水平呈正相关（P < 0.05）。IgAN患者的炎症因子水平升高。16 s rDNA分析表明，与健康受试者相比，这些患者的肠道微生物群紊乱。IgAN患者中某些菌群数量减少而某些菌群数量增加。这些菌群数量的减少与尿Gd-IgA1以及DAO、sICAM-1、D-LAC和LPS水平呈显著负相关。