Abstract: FR-PO678

MBL2 Gene Polymorphism and IgG4 in Membranous Nephropathy

Session Information

Category: Glomerular

  • 1001 Glomerular: Basic/Experimental Immunology and Inflammation

Authors

  • Costa, Denise Maria do nascimento, Hospital das Clinicas - UFPE, Recife, Pernambuco, Brazil
  • Vajgel, Gisele, Hospital das Clinicas - UFPE, Recife, Pernambuco, Brazil
  • Cavalcante, Maria Alina G.M., Hospital das Clinicas - UFPE, Recife, Pernambuco, Brazil
  • Oliveira, Camila Barbosa lyra, Hospital das Clinicas - UFPE, Recife, Pernambuco, Brazil
  • Vasconcelos, Carolina Andrade jordão, Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Pernambuco, Brazil
  • Valente, Lucila Maria, Hospital das Clinicas - UFPE, Recife, Pernambuco, Brazil
Background

Although there is evidence regarding the involvement of the lectin pathway and IgG4 in idiopathic membranous nephropathy (IMN), the trigger responsible for the immune complexes formation is uncertain. It is known that IMN occurs in genetically susceptible individuals, however, very few studies have investigated the possible relationship between this glomerulopathy and polymorphisms of the MBL2 gene, which is responsible for producing mannose-binding lectin (MBL) protein, a major component of the lectin pathway of the complement. We investigated the frequency of 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 SNPs at positions -550 (HL) and -221 (XY) in the promoter region were evaluated in 60 patients compared to a control group of 101 blood donors. It established the frequency of polymorphisms and the serum ratio of IgG4 comparing the two main etiologies of membranous nephropathy: idiopathic (35 patients) and secondary to systemic lupus erythematosus (LMN) in 25 patients.

Results

The O allele, variant of exon 1, was more frequent in the group with MN compared to CG (42% × 22%; p <0.001). The heterozygous A/O was predominant among patients with MN compared to genotype A/A (OR = 11.16; 95% CI = 4.77 - 28.41). There was no difference for genotypes or alleles frequencies among patients and CG in H/L and X/Y promoter variants. When comparing the IMN and LMN groups there was no difference in the frequency of alleles or genotypes with a specific etiology. It was possible to reconstruct combined MBL2 genotypes from 29 patients, and split in groups as high producers (HYA/HYA, HYA/ LYA, HYA/LXA, LYA/LYA and LYA/LXA), low producers (LXA/LXA, HYA/O and LYA/O) and deficient producers (LXA/O and O/O). A low-producer combined genotype was associated with a greater chance of developing MN (OR = 6.31, 95% CI = 2.26 - 19.7, p = 0.0001) when compared to CG. Serum levels of IgG4 and IgG were measured in 32 patients with IMN and 24 with LMN. The median of serum ratio IgG4 was 5% for IMN and 3% for LMN (p = 0.016).

Conclusion

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