Activation of complement system by mannan pathway and Mbl2 genotypes in patients with type 2 diabetes and nephropathy

Abstract

To add new evidence that complement activation by the mannan (lectin) pathway is involved in the pathogenesis of nephropathy in patients with type 2 diabetes, we collected blood and urine samples from 20 patients with type 2 diabetes and nephropathy and 20 apparently healthy individuals from the general population. We performed tests for complement activation analysis (CH50, APH50, C3, C4, C3d/dg, C4d, SC5b-9, MBL and genotyping of Mbl2 gene) in blood and (C3d/dg, C4d, MBL, and SC5b-9) in urine. We found significant signs of complement activation in patients with type 2 diabetes and nephropathy in blood and in urine. We also observed significant genetic differences between healthy individuals and patients with type 2 diabetes and nephropathy concerning the Mbl2 gene. Healthy individuals were apparently more heterogeneous (45 % A0 type) in presentation of the structural Mbl2 genotype, giving intermediate and low levels of MBL protein, compared to patients with type 2 diabetes and nephropathy, who had a very homogenous Mbl2 genome (75 % AA type) giving a high level of MBL production. From our data we can conclude that patients with type 2 diabetes and nephropathy presents more frequently with Mbl2 gene polymorphism giving high production of the MBL protein, what is very likely connected with acquired renal injury.

Keywords

• nephropathy, diabetes, complement, mannan binding lectin