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Fig. 3 | Autoimmunity Highlights

Fig. 3

From: Autoantibodies directed against α1-adrenergic receptor and endothelin receptor A in patients with prostate cancer

Fig. 3

a Autoantibodies directed against the α1-adrenergic receptor (α1-AAB) and endothelin receptor A (ETA-AAB) of patients with prostate cancer target the first and second extracellular receptor loops, respectively, of their related receptors. Using the bioassay of spontaneously beating cultured neonatal rat cardiomyocytes, the chronotropic activity of the patients’ IgG (α1-AAB: n = 4; ETA-AAB: n = 5) was measured in the presence or absence of the competition of peptides representing the amino acid sequence of the extracellular receptor loops. Values below the lower limit of detection (LLD; α1-AAB = Δ 4 beats/min, ETA-AAB = Δ − 4 beats/min) were displayed as half range values. b Mapping of the first extracellular loop of the α1-adrenergic receptor and the second extracellular loop of the endothelin receptor A targeted by the related autoantibodies (α1-AAB, anti-α1-adrenergic receptor autoantibodies; ETA-AAB, anti-endothelin receptor A autoantibodies) of patients with prostate cancer. Using the bioassay of spontaneously beating cultured neonatal rat cardiomyocytes, the ETA-AAB activity and α1-AAB activity (mean ± SD) of the patients’ IgG (α1-AAB: n = 4; ETA-AAB: n = 5) was measured in the presence or absence of competing peptides that overlapped to represent the first extracellular loop of the α1-adrenergic receptor (P1: FWAFGR, P2: GRVFCDV) and the second extracellular loop of the endothelin receptor A (P1: FEYRGEQ, P2: EQHKTCM, P3: MLNATSK, P4: SKFMEFY, P5: FYQDVKD). Values below the lower limit of detection (LLD; α1-AAB = Δ 4 beats/min, ETA-AAB = Δ − 4 beats/min) were displayed as half range values. c In vitro neutralization by aptamer BC007 of autoantibodies directed against the α1-adrenergic receptor (α1-AAB) endothelin receptor A (ETA-AAB) of patients with prostate cancer. Using the bioassay of spontaneously beating cultured neonatal rat cardiomyocytes, the ETA-AAB and α1-AAB chronotropic activity of the patients’ IgG (n = 5) was measured in the presence or absence of the 0.1 µmol/L aptamer BC007 (sequence: GGTTGGTGTGGTTGG) or scrambled control (sequence: GGTGGTGGTTGTGGT). Values below the lower limit of detection (LLD; α1-AAB = ∆ 4 beats/min, ETA-AAB = Δ − 4 beats/min; cut off separating healthy subjects from patients: α1-AAB = Δ 8 beats/min, ETA-AAB = Δ − 8 beats/min) were displayed as half range values

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