Mannose-Binding Lectin2 Gene Polymorphism and IgG4 in Membranous Nephropathy

Abstract

Background: Idiopathic membranous nephropathy (IMN) has been linked to the lectin pathway, IgG4 and genetic susceptibility. We investigated the frequency of mannose-binding lectin2 (MBL2) gene polymorphisms and the serum ratio of IgG4 in patients with membranous nephropathy (MN).

Methods: Polymorphisms in the exon 1 of the MBL2 gene (codons 52, 54, and 57) and single base polymorphisms at positions -550 (HL) and -221 (XY) in the promoter region were evaluated in 60 patients compared to a control group (CG) of 101 blood donors. It established the frequency of polymorphisms and the serum ratio of IgG4 comparing 2 etiologies of MN: idiopathic (35 patients) and secondary to systemic lupus erythematosus (25 patients).

Results: Patients with MN had a 2.54-fold higher probability (95% CI 1.51-4.31) of carrying the O alelle, exon 1 variant, and 11.16-fold higher probability (95% CI 4.77-28.41) of having A/O genotype when compared to CG. The frequency of polymorphisms in the promoter region was similar between the groups. Combined genotypes generally related to the defective production of MBL (YA/O, XA/O and O/O) were more frequent in patients with MN (OR 7.11; 95% CI 2.69-21.27), when compared to controls. The median of serum ratio IgG4 was 5% for idiopathic MN and 3% for lupus MN patients (p = 0.016).

Conclusions: Our data suggests that MBL2 polymorphisms may be associated with the activation of the lectin pathway by IgG4 subclass antibodies in MN.

Keywords: Lectin pathway; Complement system; Gene polymorphism; Immunology; Lupus nephritis; Membranous nephropathy.