Fichtner A, et al. - A scrutiny was carried out of the correlation between serum angiotensin II type 1 receptor antibodies (AT1R-Ab) with specific histological lesions and with graft function and survival in conjunction with overall and complement-binding donor-specific human leucocyte antigen donor-specific antibodies (HLA-DSA) in a carefully phenotyped cohort of paediatric patients. In the context of an indication biopsy, data shed light on the connection between serum AT1R-Ab positivity > 1 year post-transplant with the histopathology of antibody-mediated rejection (ABMR). It was also determined that serum AT1R-Ab positivity served as an independent non-invasive risk factor for adverse graft outcome.

Methods

• An analysis was conducted of the sera of 62 patients at the time of renal graft biopsy for clinical indication >1 year post-transplant for AT1R-Ab by enzyme-linked immunosorbent assay (ELISA) and for DSA and C1q-fixing DSA via the single-antigen bead technology.

Results

• When compared to T-cell-mediated rejection or control, serum AT1R-Ab concentration was discovered to be substantially higher in antibody-mediated rejection (ABMR).
• The receiver operating characteristic (ROC) curve analysis illustrated that the optimal AT1R-Ab cut-off value discriminating between patients with features of ABMR and those without was 9.5 U/mL.
• It was noted that 6 among 28 patients (21.4%) with ABMR were only positive for AT1R-Ab.
• A markedly higher vascular micro-inflammation score was reported in candidates with AT1R-Ab and HLA-DSA double positivity when compared to DSA-negative patients.
• In the AT1R-Ab-positive group, the 5-year graft survival was found to be only 59% vs 87% in the AT1R-Ab-negative group.
• A tendency for a more rapid decline of estimated glomerular filtration rate (eGFR) was diclosed among subjects with AT1R-Ab and HLA-DSA double positivity when compared to individuals who were only positive for AT1R-Ab or HLA-DSA.
• C1q-positive HLA-DSA, eGFR and AT1R-Ab positivity demonstrated a prominent correlation with accelerated graft function decline, as revealed via multivariate Cox regression model of non-invasive factors.