肾基底膜抗IV型胶原抗体对肾炎患者尿免疫球蛋白G水平升高的作用：肾炎患者与健康人尿液的比较

Contribution of Anti-type IV Collagen Antibodies From Kidney Basement Membrane to Increased Level of Urinary Immunoglobulin G in Nephritis Patients: A Comparison of Nephritic and Healthy Urine.

作者信息

Yokoyama Tsukao, Ishida Yukisato

机构信息

Research, Collagen Research Center, Tokyo, JPN.

Pharmacology, Tokyo Metropolitan University, Tokyo, JPN.

出版信息

Cureus. 2025 May 1;17(5):e83284. doi: 10.7759/cureus.83284. eCollection 2025 May.

DOI:10.7759/cureus.83284

PMID:40452732

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12125646/

Abstract

BACKGROUND

Abnormality in the NC1 domain (NC1) of collagen IV is often associated with nephritis. As the α5 chain is common in heterotrimeric collagen IV within kidney basement membranes, in this study, we attempted to elucidate the nephritis-associated alteration of urinary levels of anti-α5 chain NC1 antibodies in relation to those of immunoglobulin G (IgG).

METHODS

Urine samples from 19 patients (seven diabetic nephritis, six IgA nephropathy, four nephrotic syndrome, one membranous nephropathy, and one chronic glomerulonephritis) were compared with urine samples from 19 controls (healthy subjects with normal ranges for urinary protein, urinary glucose, urinary occult blood, serum creatinine, serum urea nitrogen, serum uric acid, and estimated glomerular filtration rate (eGFR)) by enzyme-linked immunosorbent assay (ELISA) (A450nm). Using ELISA, antibodies in urine samples were detected by coating the plate with urinary proteins for IgG, purified bovine NC1 for anti-NC1 antibodies (NC1Abs), and a synthesized partial peptide in the α5 chain NC1 (yp08) for anti-yp08 antibodies (yp08Abs).

RESULTS

The levels of all measured antibodies were higher in urine samples from the nephritis group (A450nm (mean ± SD): IgG: 1.154 ± 0.298, NC1Abs: 0.479 ± 0.402, yp08Abs: 0.808 ± 0.569) than from the control group (IgG: 0.728 ± 0.236, NC1Abs: 0.051 ± 0.036, yp08Abs: 0.147 ± 0.107) (p < 0.01). In addition, the proportions of NC1Abs and yp08Abs in urinary IgG were higher in the nephritis group (NC1Abs/IgG: 0.370 ± 0.292, yp08Abs/IgG: 0.627 ± 0.396) than in the control group (NC1Abs/IgG: 0.071 ± 0.044, yp08Abs/IgG: 0.197 ± 0.127) (p < 0.01). In the nephritis group, the level of IgG correlated well with that of NC1Abs and yp08Abs (IgG versus NC1Abs: p < 0.001, r = 0.7754; IgG versus yp08Abs: p < 0.001, r = 0.7860), whereas this correlation was not present in the control group.

CONCLUSION

Our results showed that NC1Abs and yp08Abs levels are raised in nephritis patients, accounting for the observed increase in IgG levels. Furthermore, antibodies against the α5 chain of collagen IV, which compose the basement membranes of the renal glomeruli and tubules, are responsible for the increased urine levels of IgG in nephritis patients.

摘要

背景

IV型胶原的NC1结构域（NC1）异常常与肾炎相关。由于α5链在肾基底膜中的三聚体IV型胶原中常见，在本研究中，我们试图阐明与免疫球蛋白G（IgG）相关的抗α5链NC1抗体尿水平的肾炎相关改变。

方法

通过酶联免疫吸附测定（ELISA）（A450nm），将19例患者（7例糖尿病肾病、6例IgA肾病、4例肾病综合征、1例膜性肾病和1例慢性肾小球肾炎）的尿液样本与19例对照（尿蛋白、尿糖、尿潜血、血清肌酐、血清尿素氮、血清尿酸和估计肾小球滤过率（eGFR）正常范围的健康受试者）的尿液样本进行比较。使用ELISA，通过用尿蛋白包被酶标板检测IgG、用纯化的牛NC1检测抗NC1抗体（NC1Abs）、用α5链NC1中的合成部分肽（yp08）检测抗yp08抗体（yp08Abs）来检测尿液样本中的抗体。

结果

肾炎组尿液样本中所有检测抗体的水平（A450nm（平均值±标准差）：IgG：1.154±0.298，NC1Abs：0.479±0.402，yp08Abs：0.808±0.569）高于对照组（IgG：0.728±0.236，NC1Abs：0.051±0.036，yp08Abs：0.147±0.107）（p<0.01）。此外，肾炎组尿IgG中NC1Abs和yp08Abs的比例（NC1Abs/IgG：0.370±0.292，yp08Abs/IgG：0.627±0.396）高于对照组（NC1Abs/IgG：0.071±0.044，yp08Abs/IgG：0.197±0.127）（p<0.01）。在肾炎组中，IgG水平与NC1Abs和yp08Abs水平相关性良好（IgG与NC1Abs：p<0.001，r=0.7754；IgG与yp08Abs：p<0.001，r=0.7860），而对照组中不存在这种相关性。