Glomerular deposition of mannose-binding lectin (MBL) indicates a novel mechanism of complement activation in IgA nephropathy.
BACKGROUND
IgA nephropathy (IgA-N) is considered the most common glomerular disease in the world and leads to renal failure in a substantial number of patients. Although many studies have looked at the pathogenesis of the disease, many points need to be clarified, including the mechanism of complement activation. Recent studies have shown that mannose-binding lectin (MBL or mannose binding protein, MBP) initiates activation of the complement cascade (lectin pathway) utilizing two types of MBP-associated serine protease, namely MASP-1 and MASP-2. The present study was undertaken to elucidate whether the lectin pathway was involved in the pathogenic mechanism of IgA-N.


METHODS
Forty-five renal biopsy cases with IgA-N, 35 cases with other forms of glomerulonephritis (GN), and normal kidney tissues were collected and an immunohistochemical study was performed using monoclonal antibodies against MBL and MASP-1. Furthermore, clinicopathological and serological features were also analysed in the patients with IgA-N.


RESULTS
Glomerular deposition of MBL, which was accompanied by MASP-1, was detected in 11 of 45 (24.4%) cases with IgA-N, while it was detected in only one case with other forms of GN. The deposited MBL/MASP-1 was observed to associate with C3b/C3c and C5b-9 but not with IgG, IgM, C1q, C4c, or properdin. Compared with MBL/MASP-1 negative cases with IgA-N, the positive cases with IgA-N were young and the renal biopsies had been performed at an early stage of the disease. No significant correlation was found between glomerular deposition of MBL/MASP-1 and proteinuria, haematuria, creatinine clearance, and serum levels of IgA, C3, or C4 at the time of renal biopsy. There were also no significant differences between MBL/MASP-1 positive cases and negative cases in the plasma levels of circulating immune complexes or soluble C5b-9.


CONCLUSIONS
The lectin pathway of complement activation, which is initiated by the MBL/MASPs complex, evidently contributes to the development of glomerular injury in a significant number of cases with IgA-N. In addition, these findings will add insight to the pathogenesis of IgA-N, including its relation to infection, since MBL plays a crucial role in the host defense against various pathogens.
Endo
M
M
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Ohi
H
H
Ohsawa
I
I
Fujita
T
T
Matsushita
M
M
Fujita
T
T
D000293:Adolescent; D000328:Adult; D000936:Antigen-Antibody Complex / Q000032:analysis; D002352:Carrier Proteins / Q000378:metabolism*; D037222:Collectins; D003167:Complement Activation / Q000502:physiology*; D015938:Complement Membrane Attack Complex / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D050606:Mannose-Binding Protein-Associated Serine Proteases; D012697:Serine Endopeptidases / Q000378:metabolism
D000936:Antigen-Antibody Complex; D002352:Carrier Proteins; D037222:Collectins; D015938:Complement Membrane Attack Complex; D050606:Mannose-Binding Protein-Associated Serine Proteases; D012697:Serine Endopeptidases