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

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Non-HLA antibodies against the angiotensin II type 1 receptor (AT1R) 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-AT1R or anti-LG3 antibodies. The aim of this study was to investigate whether pregnancy—as a model of sensitization to polymorphic proteins—induces anti-AT1R 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-AT1R 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-AT1R 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-AT1R with anti-LG3 antibody levels, either in the pregnancy or in the control samples (r2 ≤ 0.03, P ≥ 0.26). In conclusion, physiologic full-term pregnancy does not induce anti-AT1R or anti-LG3 antibodies and may even lower their levels. Therefore, anti-AT1R and anti-LG3 antibodies are likely not caused by allosensitization. The lack of correlation of anti-AT1R with anti-LG3 antibodies suggests different mechanisms of generation, which remain to be elucidated.

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