Human pregnancy and generation of anti-angiotensin receptor and anti-perlecan antibodies

Transpl Int. 2014 May;27(5):467-74. doi: 10.1111/tri.12282. Epub 2014 Mar 12.

Abstract

Non-HLA antibodies against the angiotensin II type 1 receptor (AT1 R) and the C-terminal fragment of perlecan (i.e., LG3) are associated with the development of renal allograft rejection. It is currently unknown how humans develop anti-AT1 R or anti-LG3 antibodies. The aim of this study was to investigate whether pregnancy-as a model of sensitization to polymorphic proteins-induces anti-AT1 R and/or anti-LG3 antibodies. We included 104 samples from women obtained after physiologic full-term pregnancy and 80 samples from healthy nonsensitized controls (40 women and 40 men). Both anti-AT1 R and anti-LG3 antibody levels were lower in pregnancy samples than in controls (both P < 0.05). By multivariate analysis, male gender was an independent predictor for high anti-AT1 R antibody levels (OR 3.66, P = 0.04) and pregnancy was predictive for low anti-LG3 antibody levels (OR 6.53, P = 0.0001). There was no correlation of anti-AT1 R with anti-LG3 antibody levels, either in the pregnancy or in the control samples (r(2) ≤ 0.03, P ≥ 0.26). In conclusion, physiologic full-term pregnancy does not induce anti-AT1 R or anti-LG3 antibodies and may even lower their levels. Therefore, anti-AT1 R and anti-LG3 antibodies are likely not caused by allosensitization. The lack of correlation of anti-AT1 R with anti-LG3 antibodies suggests different mechanisms of generation, which remain to be elucidated.

Keywords: anti-angiotensin receptor antibodies; anti-perlecan antibodies; antibody-mediated rejection; non-HLA antibodies; pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / biosynthesis*
  • Female
  • HLA Antigens / immunology
  • Heparan Sulfate Proteoglycans / immunology*
  • Humans
  • Isoantibodies / biosynthesis
  • Male
  • Middle Aged
  • Peptide Fragments / immunology*
  • Pregnancy / immunology*
  • Receptor, Angiotensin, Type 1 / immunology*

Substances

  • Autoantibodies
  • HLA Antigens
  • Heparan Sulfate Proteoglycans
  • Isoantibodies
  • Peptide Fragments
  • Receptor, Angiotensin, Type 1
  • perlecan