Polymorphisms in the lectin pathway of complement activation influence the incidence of acute rejection and graft outcome after kidney transplantation

Kidney Int. 2016 Apr;89(4):927-38. doi: 10.1016/j.kint.2015.11.025. Epub 2016 Feb 3.

Abstract

There are conflicting data on the role of the lectin pathway of complement activation and its recognition molecules in acute rejection and outcome after transplantation. To help resolve this we analyzed polymorphisms and serum levels of lectin pathway components in 710 consecutive kidney transplant recipients enrolled in the nationwide Swiss Transplant Cohort Study, together with all biopsy-proven rejection episodes and 1-year graft and patient survival. Functional mannose-binding lectin (MBL) levels were determined in serum samples, and previously described MBL2, ficolin 2, and MBL-associated serine protease 2 polymorphisms were genotyped. Low MBL serum levels and deficient MBL2 diplotypes were associated with a higher incidence of acute cellular rejection during the first year, in particular in recipients of deceased-donor kidneys. This association remained significant (hazard ratio 1.75, 95% confidence interval 1.18-2.60) in a Cox regression model after adjustment for relevant covariates. In contrast, there was no significant association with rates of antibody-mediated rejection, patient death, early graft dysfunction or loss. Thus, results in a prospective multicenter contemporary cohort suggest that MBL2 polymorphisms result in low MBL serum levels and are associated with acute cellular rejection after kidney transplantation. Since MBL deficiency is a relatively frequent trait in the normal population, our findings may lead to individual risk stratification and customized immunosuppression.

Keywords: acute rejection; cohort study; innate immunity; kidney transplantation; mannose-binding lectin.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Complement Pathway, Mannose-Binding Lectin
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Graft Rejection / epidemiology
  • Graft Rejection / genetics*
  • Humans
  • Incidence
  • Kidney Transplantation*
  • Lectins / genetics*
  • Male
  • Mannose-Binding Lectin / blood
  • Mannose-Binding Lectin / genetics*
  • Mannose-Binding Protein-Associated Serine Proteases / genetics*
  • Middle Aged
  • Polymorphism, Genetic
  • Switzerland / epidemiology

Substances

  • Lectins
  • MBL2 protein, human
  • Mannose-Binding Lectin
  • ficolin
  • MASP2 protein, human
  • Mannose-Binding Protein-Associated Serine Proteases