Regulation of in situ complement activation via the lectin pathway in patients with IgA nephropathy.
The lectin pathway, which is initiated by mannose-binding lectin (MBL) and MBL-associated serine protease (MASP), is one of the possible routes to activate the complement cascade in immunoglobulin A (IgA) nephropathy. The purpose of this study was to elucidate the regulatory mechanism of the pathway. Levels of complement activation products and regulatory proteins were measured in sera from 27 patients with IgA nephropathy, and generation of fluid-phase complement activation products in the presence of pooled normal human serum was quantified to evaluate activation in vitro. Although there were no significant differences in the serum levels and in vitro activation between the MBL-MASP positive (n = 14) and negative (n = 13) groups, there were positive correlations between complement activation products (Bb fragment and C4d fragment) and regulatory proteins (factor H, C4-binding protein, and C1 inhibitor) in the MBL-MASP-positive group. Furthermore, immunohistochemical studies demonstrated glomerular deposition of the regulatory protein (C4-binding protein, alpha2-macroglobulin, and factor H) in all patients in the MBL-MASP-positive group. These findings suggest that the regulatory proteins control in situ complement activation via the lectin pathway immediately, and continuous activation due to inadequate control will lead to the advanced glomerular injury.
Endo
M
M
The 2nd Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. mendo@med.nihon-u.ac.jp
Ohi
H
H
Satomura
A
A
Hidaka
M
M
Ohsawa
I
I
Fujita
T
T
Kanmatsuse
K
K
Matsushita
M
M
Fujita
T
T
D002352:Carrier Proteins / Q000097:blood / Q000502:physiology*; D037222:Collectins; D003167:Complement Activation; D003174:Complement C1 Inactivator Proteins / Q000032:analysis; D051561:Complement C3 Convertase, Alternative Pathway; D003179:Complement C3b / Q000032:analysis; D015932:Complement C3c / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D017242:Complement Factor H / Q000032:analysis; D005260:Female; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D016167:Integrin alphaXbeta2 / Q000097:blood; D007678:Kidney Glomerulus / Q000276:immunology; D037102:Lectins / Q000097:blood; D008297:Male; D050606:Mannose-Binding Protein-Associated Serine Proteases; D010446:Peptide Fragments / Q000032:analysis; D012697:Serine Endopeptidases / Q000097:blood / Q000502:physiology*; D000511:alpha-Macroglobulins / Q000032:analysis
C493495:CFH protein, human; D002352:Carrier Proteins; D037222:Collectins; D003174:Complement C1 Inactivator Proteins; D003181:Complement C4; D016167:Integrin alphaXbeta2; D037102:Lectins; D010446:Peptide Fragments; D000511:alpha-Macroglobulins; D003179:Complement C3b; D015932:Complement C3c; D017242:Complement Factor H; D050606:Mannose-Binding Protein-Associated Serine Proteases; D012697:Serine Endopeptidases; D051561:Complement C3 Convertase, Alternative Pathway