Deposition of mannan binding protein and mannan binding protein-mediated complement activation in the glomeruli of patients with IgA nephropathy.
Mannan binding protein (MBP) is a C-type lectin and has a high affinity to mannose and N-acetyl glucosamine. It is also known to activate C4 and C2 without C1 component, which is called 'lectin pathway'. We now report the presence of MBP and MBP-mediated complement activation in renal glomeruli of IgA nephropathy patients using an immunohistochemical method. In 7 of 42 cases with IgA nephropathy, MBP was detected in the glomerular mesangial area and colocalized with IgA1. In 19 cases with other types of IC-mediated glomerulonephritis including lupus nephritis and membranous nephropathy or without nephritis, MBP was not detected in the glomerulus. The C2- and/or C4-positive rate was 87.5% in the MBP-positive group and 20% in the MBP-negative group of IgA nephropathy. In addition, MBP-positive cases showed marked mesangial cell proliferation, lower creatinine clearance (53.4 +/- 10.0 vs. 77. 8 +/- 4.7 ml/min) and higher urinary protein excretion (2.5 +/- 0.9 vs. 0.9 +/- 0.2 g/day) compared with MBP-negative cases. These findings suggested that MBP was involved in glomerular complement activation through the lectin pathway and thus induced glomerular injury of IgA nephropathy. Since oligosaccharide chain alterations such as reduced sialic acid and galactose of IgA1 molecule have been reported in IgA nephropathy patients, MBP might bind to the IgA1 molecule via interaction between MBP and sugar chain.
Matsuda
M
M
Department of Medicine III, Okayama University Medical School, Okayama, Japan.
Shikata
K
K
Wada
J
J
Sugimoto
H
H
Shikata
Y
Y
Kawasaki
T
T
Makino
H
H
D000328:Adult; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D037222:Collectins; D003167:Complement Activation / Q000502:physiology*; D003175:Complement C2 / Q000378:metabolism / Q000502:physiology; D003181:Complement C4 / Q000378:metabolism / Q000502:physiology; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged
D002352:Carrier Proteins; D037222:Collectins; D003175:Complement C2; D003181:Complement C4