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.

1.
Kawasaki T, Etoh R, Yamashina I: Isolation and characterization of a mannan-binding protein from rabbit liver. Biochem Biophys Res Commun 1978;81:1018–1024.
2.
Kawasaki N, Kawasaki T, Yamashina I: Isolation and characterization of a mannan-binding protein from human serum. J Biochem 1983;94:937–947.
3.
Ohta M, Okada M, Yamashina I, Kawasaki T: The mechanism of carbohydrate-mediated complement activation by the serum mannan-binding protein. J Biol Chem 1990;265:1980–1984.
4.
Drickamer K: Engineering galactose-binding activity into a C-type mannose-binding protein. Nature 1992;360:183–186.
5.
Turner MW: Mannose binding protein. Biochem Soc Trans 1994;22:88–94.
6.
Holmskov U, Malhotra R, Sim RB, Jensenius JC: Collectins: Collagenous C-type lectins of the innate immune defense system. Immunol Today 1994;15:67–73.
7.
Garred P, Thiel S, Madsen HO, Ryder LP, Jensenius JC, Svejgaard A: Gene frequency and partial protein characterization of an alleic variant of mannan binding protein associated with low serum concentrations. Clin Exp Immunol 1992;90:517–521.
8.
Turner MW, Lipscombe RJ, Levinsky RJ, Lau YL, Hill AVS, Summerfield JA, Sumiya M: Mutations in the human mannose binding protein gene: Their frequencies in three distinct populations and relationship to serum levels of the protein. Immunodeficiency 1993;4:285–287.
9.
Terai I, Kobayashi K, Fujita T, Hagiwara K: Human serum mannose binding protein (MBP): Development of an enzyme-linked immunosorbent assay (ELISA) and determination of levels in serum from 1085 normal Japanese and in some body fluids. Biochem Med Metab Biol 1993;50:111–119.
10.
Summerfield JA, Ryder S, Sumiya M, Thursz M, Gorchein A, Monteil MA, Turner MW: Mannose binding protein gene mutations associated with unusual and severe infections in adults. Lancet 1995;345:886–889.
11.
Tabona P, Mellor A, Summerfield JA: Mannose binding protein is involved in first-line host defence: Evidence from transgenic mice. Immunology 1995;85:153–159.
12.
Malhotra R, Wormald MR, Rudd PM, Fischer PB, Dwek RA, Sim RB: Glycosylation changes of IgG associated with rheumatoid arthritis can activate complement via the mannose-binding protein. Nat Med 1995;1:237–243.
13.
Baharaki D, Dueymes M, Perrichot R, Basset C, Corre RL, Cledes J, Youinou P: Aberrant glycosylation of IgA from patients with IgA nephropathy. Glycoconj J 1996;13:505–511.
14.
Matsuda M, Shikata K, Makino H, Sugimoto H, Ota Z: Glomerular expression of macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in patients with various forms of glomerulonephritis. Lab Invest 1996;75:403–412.
15.
Matsuda M, Shikata K, Makino H, Sugimoto H, Ota K, Akiyama K, Hirata K, Ota Z: Gene expression of PDGF and PDGF receptor in various forms of glomerulonephritis. Am J Nephrol 1997;17:25–31.
16.
Makino H, Gibbons JT, Reddy MK, Kanwar YS: Nephritogenicity of antibodies to proteoglycans of the glomerular basement membrane. Part 1. J Clin Invest 1986;77:142–156.
17.
Lee SM, Rao VM, Franklin WA, Schiffer MS, Aronson AJ, Spargo BH, Katz AI: IgA nephropathy: Morphologic predictors of progressive renal disease. Hum Pathol 1982;13:314–322.
18.
Rudd PM, Fortune F, Patel T, Parekh RB, Dwek RA, Lehner T: A human T-cell receptor recognizes O-linked sugars from the hinge region of human IgA1 and IgD. Immunology 1994;83:99–106.
19.
Hiki Y, Horii A, Iwase H, Tanaka A, Toda Y, Hotta K, Kobayashi Y: O-linked oligosaccharide on IgA1 hinge region in IgA nephropathy. Contrib Nephrol 1995;111:73–84.
20.
Tomana M, Matousovic K, Julian BA, Radl J, Konecny K, Mestecky J: Galactose-deficient IgA1 in sera of IgA nephropathy patients is present in complexes with IgG. Kidney Int 1997;52:509–516.
21.
Suzuki S, Nakatomi Y, Sato H, Tsukada H, Arakawa M: Haemophilus parainfluenzae antigen and antibody in renal biopsy samples and serum of patients with IgA nephropathy. Lancet 1994;343:12–16.
22.
Masuda Y, Terazawa K, Kawakami S, Ogura Y, Sugiyama N: Clinical and immunological study of IgA nephropathy before and after tonsillectomy. Acta Otolaryngol Suppl 1988;454:248–255.
23.
Yamabe H, Osawa H, Inuma H, Kaizuka M, Tamura N, Tsunoda S, Fujita Y, Shirato K, Onodera K: Deterioration of urinary findings after tonsil stimulation in patients with IgA nephropathy. Acta Otolaryngol Suppl 1996;523:169–171.
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