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

Non-HLA antibodies against the angiotensin II type 1 receptor (AT(1)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-AT(1)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-AT(1)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-AT(1)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-AT(1)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-AT(1)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-AT(1)R or anti-LG3 antibodies and may even lower their levels. Therefore, anti-AT(1)R and anti-LG3 antibodies are likely not caused by allosensitization. The lack of correlation of anti-AT(1)R with anti-LG3 antibodies suggests different mechanisms of generation, which remain to be elucidated.