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


CONCLUSIONS
S. aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy.
Koyama
Akio
A
Institute of Clinical Medicine, Department of Nephrology, University of Tsukuba, Ibaraki, Japan. a-koyama@md.tsukuba.ac.jp
Sharmin
Samina
S
Sakurai
Hideko
H
Shimizu
Yoshio
Y
Hirayama
Kouichi
K
Usui
Joichi
J
Nagata
Michio
M
Yoh
Keigyou
K
Yamagata
Kunihiro
K
Muro
Kaori
K
Kobayashi
Masaki
M
Ohtani
Kaori
K
Shimizu
Takeshi
T
Shimizu
Tohru
T
D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000276:immunology; D000942:Antigens, Bacterial / Q000032:analysis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005455:Fluorescent Antibody Technique; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis / Q000378:metabolism; D007074:Immunoglobulin G / Q000032:analysis / Q000378:metabolism; D007668:Kidney / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology; D008969:Molecular Sequence Data; D013211:Staphylococcus aureus / Q000276:immunology*; D014018:Tissue Distribution
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D000939:Epitopes; D007070:Immunoglobulin A; D007074:Immunoglobulin G