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.

[1]  B. Julian,et al.  Galactose-deficient IgA1 in sera of IgA nephropathy patients is present in complexes with IgG. , 1997, Kidney international.

[2]  H. Makino,et al.  Glomerular expression of macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in patients with various forms of glomerulonephritis. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[3]  Y. Hiki,et al.  O-Linked Oligosaccharide on IgA1 Hinge Region in IgA Nephropathy1 , 1995 .

[4]  M. Turner,et al.  Mannose binding protein gene mutations associated with unusual and severe infections in adults , 1995, The Lancet.

[5]  R. Dwek,et al.  Glycosylation changes of IgG associated with rheumatooid arthritis can activate complement via the mannose-binding protein , 1995, Nature Medicine.

[6]  R. Dwek,et al.  A human T-cell receptor recognizes 'O'-linked sugars from the hinge region of human IgA1 and IgD. , 1994, Immunology.

[7]  J. Jensenius,et al.  Collectins: collagenous C-type lectins of the innate immune defense system. , 1994, Immunology today.

[8]  M. Turner.  Mannose binding protein. , 1994, Biochemical Society transactions.

[9]  M. Arakawa,et al.  Haemophilus parainfluenzae antigen and antibody in renal biopsy samples and serum of patients with IgA nephropathy , 1994, The Lancet.

[10]  K. Kobayashi,et al.  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. , 1993, Biochemical medicine and metabolic biology.

[11]  S. Thiel,et al.  Gene frequency and partial protein characterization of an allelic variant of mannan binding protein associated with low serum concentrations , 1992, Clinical and experimental immunology.

[12]  K. Drickamer.  Engineering galactose-binding activity into a C-type mannose-binding protein , 1992, Nature.

[13]  M. Okada,et al.  The mechanism of carbohydrate-mediated complement activation by the serum mannan-binding protein. , 1990, The Journal of biological chemistry.

[14]  T. Kawasaki,et al.  Isolation and characterization of a mannan-binding protein from human serum. , 1983, Journal of biochemistry.

[15]  A. Katz,et al.  IgA nephropathy: morphologic predictors of progressive renal disease. , 1982, Human pathology.

[16]  Y. Kozutsumi,et al.  Isolation and characterization of a mannan-binding protein from rabbit serum. , 1978, Biochemical and biophysical research communications.

[17]  H. Makino,et al.  Gene expression of PDGF and PDGF receptor in various forms of glomerulonephritis. , 1997, American journal of nephrology.

[18]  K. Shirato,et al.  Deterioration of urinary findings after tonsil stimulation in patients with IgA nephropathy. , 1996, Acta oto-laryngologica. Supplementum.

[19]  J. Summerfield,et al.  Mannose binding protein is involved in first-line host defence: evidence from transgenic mice. , 1995, Immunology.

[20]  Y. Hiki,et al.  O-linked oligosaccharide on IgA1 hinge region in IgA nephropathy. Fundamental study for precise structure and possible role. , 1995, Contributions to nephrology.

[21]  Y. Lau,et al.  Mutations in the human mannose binding protein gene: their frequencies in three distinct populations and relationship to serum levels of the protein. , 1993, Immunodeficiency.

[22]  Y. Ogura,et al.  Clinical and immunological study of IgA nephropathy before and after tonsillectomy. , 1988, Acta oto-laryngologica. Supplementum.

[23]  H. Makino,et al.  Nephritogenicity of antibodies to proteoglycans of the glomerular basement membrane--I. , 1986, The Journal of clinical investigation.

[24]  T. Kawasaki,et al.  Isolation and characterization of a mannan-binding protein from rabbit liver. , 1978, Biochemical and biophysical research communications.