肾小球肾炎中补体C4同种型C4A和C4B在肾小球的沉积。

Glomerular deposition of the complement C4 isotypes C4A and C4B in glomeruonephritis.

作者信息

Lhotta K, Schlogl A, Kronenberg F, Joannidis M, Konig P

机构信息

Department of Internal Medicine, Innsbruck University Hospital and Instute of Medical Biology and Human Genetics, University of Innsbruck, Austria.

出版信息

Nephrol Dial Transplant. 1996 Jun;11(6):1024-8.

PMID:8671963

Abstract

BACKGROUND

Complement C4 is a component of the classical complement pathway, which is a major mediator of inflammation in many forms of glomerulonephritis. The two isoforms of C4-C4A and C4B-differ in their physicochemical and functional properties.

METHODS

The glomerular deposition of C4A and C4B was investigated in 39 cases of glomerulonephritis with classical pathway activation using isotype-specific monoclonal antibodies 99H7 (C4A) and 1288 (C4B) and indirect immunofluorescence. Complement C4 phenotypes of all patients were determined by agarose gel electrophoresis and immunoprecipitation.

RESULTS

Three biopsies contained only the isotype C4B. C4 phenotyping revealed complete C4A deficiency in these three patients. Both isotypes C4A and C4B were detected in 36 biopsies. In 19 (53%) thereof staining for both isotypes was identical. In the remaining 17 (47%), staining intensity of C4A predominated over C4B. The distribution of these two staining patterns did not differ between membranous glomerulonephritis and lupus nephritis. They were also independent of C4A and C4B allotypes including the presence or absence of null alleles at either gene locus. In no case was C4B staining stronger than C4A staining. Serum creatinine and proteinuria did not differ between patients with identical and C4A-dominant C4 deposition.

CONCLUSIONS

The most likely but still hypothetical explanation for predominance in glomerular deposition of C4A over C4B in many cases of immune complex-mediated glomerulonephritis is the greater affinity of C4A to protein-containing immune complexes as compared to C4B.

摘要

背景

补体C4是经典补体途径的一个组成部分，在多种形式的肾小球肾炎中是炎症的主要介质。C4的两种同种型——C4A和C4B——在物理化学和功能特性上有所不同。

方法

使用同种型特异性单克隆抗体99H7（C4A）和1288（C4B）及间接免疫荧光法，对39例经典途径激活的肾小球肾炎患者的肾小球C4A和C4B沉积情况进行了研究。通过琼脂糖凝胶电泳和免疫沉淀法测定所有患者的补体C4表型。

结果

3份活检标本仅含有同种型C4B。C4表型分析显示这3例患者存在完全的C4A缺陷。36份活检标本中均检测到C4A和C4B两种同种型。其中19份（53%）两种同种型的染色相同。在其余17份（47%）中，C4A的染色强度高于C4B。这两种染色模式的分布在膜性肾小球肾炎和狼疮性肾炎之间没有差异。它们也与C4A和C4B的异型无关，包括任一基因位点是否存在无效等位基因。在任何情况下，C4B的染色都不会强于C4A的染色。C4沉积相同和C4A占优势的患者之间血清肌酐和蛋白尿没有差异。