title: Human pregnancy and generation of anti-angiotensin receptor and anti-perlecan antibodies.
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.
authors.affiliation: Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
authors.forename: Gideon
authors.initials: G
authors.lastname: Hönger
authors.forename: Heloise
authors.initials: H
authors.lastname: Cardinal
authors.forename: Mélanie
authors.initials: M
authors.lastname: Dieudé
authors.forename: Andreas
authors.initials: A
authors.lastname: Buser
authors.forename: Irene
authors.initials: I
authors.lastname: Hösli
authors.forename: Duska
authors.initials: D
authors.lastname: Dragun
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Hébert
authors.forename: Stefan
authors.initials: S
authors.lastname: Schaub
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000096:biosynthesis*; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D019812:Heparan Sulfate Proteoglycans / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*; D011247:Pregnancy / Q000276:immunology*; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens; D019812:Heparan Sulfate Proteoglycans; D007518:Isoantibodies; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; C071927:perlecan
keywords: anti-angiotensin receptor antibodies; anti-perlecan antibodies; antibody-mediated rejection; non-HLA antibodies; pregnancy