Nephrology Dialysis Transplantation, Vol 13, Issue 8 1984-1990, Copyright © 1998 by Oxford University Press
M Endo, H Ohi, I Ohsawa, T Fujita, M Matsushita and T Fujita
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, Clq, 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. Conclusion. 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 defence against various pathogens.
Keywords: complement; IgA nephropathy; mannose-binding
lectin; mannose-binding lectin associated serine protease
ORIGINAL ARTICLES
Glomerular deposition of mannose-binding lectin (MBL) indicates a novel mechanism of complement activation in IgA nephropathy
Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan; Department of Biochemistry, Fukushima Medical College, Fukushima, Japan; Correspondence to: M Endo, Second Department of Internal Medicine, Nihon University School of Medicine, 30-1, Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173, Japan
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