AT1R-Ab have been associated with kidney allograft rejection; however, their ability to induce a specific rejection phenotype, independent of HLA-DSAs, has not been defined.

In a prospective cohort of 881 kidney recipients (2007-2010), we performed systematic screening for AT1R-Ab using quantitative ELISA and HLA-DSAs, together with concomitant allograft biopsy, at the time of any clinical event in the first-year post-transplant and at 1 year post-transplant. The allograft rejection phenotype was assessed by histopathology, immunochemistry for C4d, and allograft gene expression measurement using microarray.

We identified 233/881 (26%) pts with post-transplant AT1R-Ab (>10 U/mL). Compared to AT1R-Ab negative pts, AT1R-Ab positive pts showed increased levels of glomerulitis (p=0.01), peritubular capillaritis (p=0.01), endarteritis (p=0.01), similar level of interstitial inflammation (p=0.66) and tubulitis (p=0.23), and similar prevalence of C4d deposition (p=0.24) and TG (p=0.99). After adjusting for HLA-DSAs, AT1R-Ab were independently associated with glomerulitis (aOR=1.7, p=0.006), peritubular capillaritis (aOR=1.8, p=0.002) and intimal arteritis (aOR=2.1, p=0.01). Among pts with microcirculation inflammation (g+ptc>1) (N=154), AT1R-Ab+/HLA-DSA- pts (N=23) showed increased prevalence of intimal arteritis (39%) and decreased prevalence of C4d positivity (17%) compared to AT1R-Ab-/HLA-DSA+ pts (N=80, 13% and 51%, respectively), AT1R-Ab+/HLA-DSA+ pts (N=31, 16% and 55%, respectively) and AT1R-Ab-/HLA-DSA- pts (N=20, 5% and 10%, respectively) (p<0.001 and p=0.01, respectively). Compared to AT1R-Ab-/HLA-DSA+ pts, AT1R-Ab+/HLA-DSA- pts had increased expression of endothelial cell associated transcripts in allograft, including MEOX2, MEOX1 and FOSB (FC=3.9, 3.0 and 2.7, respectively, p<0.001 for all). Histomolecular rejection phenotype in AT1R-Ab+/HLA-DSA- pts was distinct from that of AT1R-Ab-/HLA-DSA+ pts in unsupervised clustering.

AT1R-Ab are associated with a specific histo-molecular phenotype of kidney allograft rejection, characterized by microvascular and arterial inflammation, expression of endothelial cell associated transcripts and low prevalence of complement deposition in capillaries, independent of HLA-DSAs.

CITATION INFORMATION: Lefaucheur C., Viglietti D., Aubert O., Philippe A., Halloran P., Loupy A., Dragun D. Anti-Angiotensin II Type 1-Receptor Antibodies (AT1R-Ab) Induce a Specific Phenotype of Rejection Distinct from HLA Antibody-Mediated Rejection Am J Transplant. 2017;17 (suppl 3).

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