金黄色葡萄球菌细胞壁抗原是诱导IgA肾病的新候选因素。

Staphylococcus aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy.

作者信息

Koyama Akio, Sharmin Samina, Sakurai Hideko, Shimizu Yoshio, Hirayama Kouichi, Usui Joichi, Nagata Michio, Yoh Keigyou, Yamagata Kunihiro, Muro Kaori, Kobayashi Masaki, Ohtani Kaori, Shimizu Takeshi, Shimizu Tohru

机构信息

Institute of Clinical Medicine, Department of Nephrology, University of Tsukuba, Ibaraki, Japan.

出版信息

Kidney Int. 2004 Jul;66(1):121-32. doi: 10.1111/j.1523-1755.2004.00714.x.

DOI:10.1111/j.1523-1755.2004.00714.x

PMID:15200419

Abstract

BACKGROUND

IgA nephropathy is the most common form of glomerulonephritis worldwide. We previously reported a novel form of glomerulonephritis with glomerular IgA deposits following methicillin-resistant Staphylococcus aureus (S. aureus) infection. We investigated the role of S. aureus related antigens in the immunopathogenesis of IgA nephropathy by producing several monoclonal antibodies against S. aureus surface antigens and determining the epitopes of deposited antigens in patients with IgA nephropathy.

METHODS

Cell membrane proteins were isolated from cultured S. aureus. Mouse monoclonal antibodies against these proteins were generated, and their target epitopes were determined by antibody affinity chromatography and amino acid sequence analysis, and by monoclonal antibody screening of Escherichia coli clones transfected with plasmids from the Lambda S. aureus Genomic Library. Renal biopsy specimens from 116 patients with IgA nephropathy and 122 patients with other forms of renal disease were examined for glomerular antigen depositions by immunofluorescence microscopy.

RESULTS

. The major antigen recognized by monoclonal antibodies against S. aureus cell membrane was identified as the S. aureus cell envelope antigen designated 'probable adhesin' (ACCESSION AP003131-77, Protein ID; BAB41819.1). In 68.1% (79/116) of renal biopsy specimens from patients with IgA nephropathy, S. aureus cell envelope antigen was localized in the glomeruli, and the data confirmed that S. aureus cell envelope antigen was co-localized with IgA antibody in the glomeruli. No deposition of this antigen was detected in the glomeruli of patients with non-immune complex deposit forms of glomerulonephritis.

CONCLUSION

S. aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy.

摘要

背景

IgA肾病是全球最常见的肾小球肾炎形式。我们之前报道了一种新型肾小球肾炎，其在耐甲氧西林金黄色葡萄球菌（金黄色葡萄球菌）感染后出现肾小球IgA沉积。我们通过制备几种针对金黄色葡萄球菌表面抗原的单克隆抗体并确定IgA肾病患者中沉积抗原的表位，研究了金黄色葡萄球菌相关抗原在IgA肾病免疫发病机制中的作用。

方法

从培养的金黄色葡萄球菌中分离细胞膜蛋白。制备针对这些蛋白的小鼠单克隆抗体，并通过抗体亲和层析和氨基酸序列分析，以及对用来自λ金黄色葡萄球菌基因组文库的质粒转染的大肠杆菌克隆进行单克隆抗体筛选来确定其靶表位。通过免疫荧光显微镜检查116例IgA肾病患者和122例其他形式肾病患者的肾活检标本中的肾小球抗原沉积情况。

结果

针对金黄色葡萄球菌细胞膜的单克隆抗体识别的主要抗原被鉴定为金黄色葡萄球菌细胞包膜抗原，命名为“可能的黏附素”（登录号AP003131 - 77，蛋白质ID；BAB41819.1）。在IgA肾病患者的肾活检标本中，68.1%（79/116）的标本中金黄色葡萄球菌细胞包膜抗原定位于肾小球，数据证实金黄色葡萄球菌细胞包膜抗原在肾小球中与IgA抗体共定位。在非免疫复合物沉积形式肾小球肾炎患者的肾小球中未检测到该抗原的沉积。