Nephritis-associated plasmin receptor and acute poststreptococcal glomerulonephritis: characterization of the antigen and associated immune response.
The role of nephritis-associated antigen as a virulence factor for acute poststreptococcal glomerulonephritis (APSGN) remains to be fully clarified. Nephritis-associated plasmin receptor (NAPlr) was previously isolated from group A streptococcus (GAS) and shown to bind plasmin(ogen). The nucleotide sequence of the naplr gene from GAS isolates obtained from patients with APSGN was determined. The sequence of the putative open reading frame (1011 bp) showed 99.8% identity among isolated strains. Homology screen revealed an exact match with streptococcal glyceraldehyde-3-phosphate dehydrogenase (GAPDH). NAPlr exhibited GAPDH activity in zymography, and it activated the complement pathway in vitro. In APSGN kidney biopsy specimens, NAPlr was observed mainly in the early stage of the disease (1 to 14 d after onset) but was not colocalized with either C3 or IgG as assessed by double immunofluorescence staining. Sera of patients with APSGN, patients with GAS infection without renal involvement, nonrenal pediatric patients, and healthy adults as controls were assayed for anti-NAPlr antibody titers. Anti-NAPlr antibodies were present most frequently in APSGN sera, and antibody titers were also significantly higher than in patients with GAS infection alone or in other control patients. Moreover, antibody titers remained elevated during the entire 10-yr follow-up period.
Yoshizawa
Nobuyuki
N
Department of Public Health, National Defense Medical College, Saitama, Japan. yoshizawa-npr@umin.ac.jp
Yamakami
Kazuo
K
Fujino
Masayuki
M
Oda
Takashi
T
Tamura
Kikuko
K
Matsumoto
Koichi
K
Sugisaki
Tetsuzo
T
Boyle
Michael D P
MD
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005921:Glomerulonephritis / Q000209:etiology* / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D008969:Molecular Sequence Data; D009393:Nephritis / Q000473:pathology*; D016366:Open Reading Frames; D018000:Receptors, Peptide / Q000096:biosynthesis*; D017422:Sequence Analysis, DNA; D013290:Streptococcal Infections / Q000276:immunology*; D013997:Time Factors
D003176:Complement C3; D007074:Immunoglobulin G; D018000:Receptors, Peptide; C065181:plasmin receptor