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 wi thout C1 component, which is called 'lectin pathway'. We now report the pre sence of MBP and MBP-mediated complement activation in renal glomeruli of I gA nephropathy patients using an immunohistochemical method. In 7 of 42 cas es with IgA nephropathy, MBP was detected in the glomerular mesangial area and colocalized with IgA1. In 19 cases with other types of IC-mediated glom erulonephritis including lupus nephritis and membranous nephropathy or with out nephritis, MBP was not detected in the glomerulus. The C2- and/or C4-po sitive 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 me sangial cell proliferation, lower creatinine clearance (53.4 +/- 10.0 vs. 7 7.8 +/- 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 suggeste d that MBP was involved in glomerular complement activation through the lec tin pathway and thus induced glomerular injury of IgA nephropathy. Since ol igosaccharide chain alterations such as reduced sialic acid and galactose o f IgA1 molecule have been reported in IgA nephropathy patients, MBP might b ind to the IgA1 molecule via interaction between MBP and sugar chain.