The Detection of Antibodies to the Angiotensin II-Type 1 Receptor in Transplantation

Dragun, Duska

doi:10.1007/978-1-62703-493-7_19

Cited by 9 publications

(6 citation statements)

References 5 publications

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“…C4d scores were not significantly different among the 3 groups, and this is in agreement with most AT1R-Ab studies. 24 - 26 It is now recognized that antibody mediated injury may occur in the absence of detectable complement activation 27 through such mechanisms as antibody dependent cell mediated cytotoxicity or antibody mediated endothelial cell activation. 12 , 28 , 29 …”

Section: Discussionmentioning

confidence: 99%

Anti-Angiotensin II Type 1 Receptor and Anti-Endothelial Cell Antibodies: A Cross-Sectional Analysis of Pathological Findings in Allograft Biopsies

Philogene

Bagnasco²,

Kraus³

et al. 2017

Transplantation

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BackgroundThis is a cross-sectional study designed to evaluate the histologic characteristics of graft injury in the presence of anti-angiotensin II type 1 receptor antibody (AT1R-Ab) and anti-endothelial cell antibody (AECA).MethodsNon-HLA antibody testing was included in the posttransplant evaluation for 70 kidney recipients. Biopsies were performed for cause for 47 patients and as protocol for the remaining 23 patients. Biopsy-proven rejection was defined according to the Banff 2009-2013 criteria. AT1R-Ab was measured on an ELISA platform. Patients were divided into 3 groups based on AT1R-Ab levels (>17, 10-17, and <10 U/ml). AECA was evaluated using an endothelial cell crossmatch (ECXM) in patients whose HLA antibody level was insufficient to cause a positive flow cytometric crossmatch.ResultsAT1R-Ab levels were higher in patients diagnosed with antibody mediated rejection compared to those with no rejection (P = 0.004). Glomerulitis (g) and peritubular capillaritis (ptc) scores were independently correlated with increased AT1R-Ab concentrations in the presence or absence of HLA-DSA (P = 0.007 and 0.03 for g scores; p = 0.005 and 0.03 for ptc scores). Patients with a positive ECXM had higher AT1R-Ab levels compared to those with a negative ECXM (P = 0.005). Microcirculation inflammation (MCI = g + ptc score) was higher in patients with a positive ECXM and with AT1R-Ab >17 U/ml, although this did not reach statistical significance (P = 0.07).ConclusionsThe data show an association between non-HLA antibodies detected in the ECXM and AT1R ELISA and microvascular injury observed in antibody mediated rejection.

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Section: Discussionmentioning

confidence: 99%

Anti-Angiotensin II Type 1 Receptor and Anti-Endothelial Cell Antibodies: A Cross-Sectional Analysis of Pathological Findings in Allograft Biopsies

Philogene

Bagnasco²,

Kraus³

et al. 2017

Transplantation

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“…In order to obtain a standard curve, plates were incubated with a ready-to use standard at 2.5, 5, 10, 20, and 40 U/ml. The assay was validated as compared to a cardiomyocyte bioassay (for further assay details see also Dragun) [ 43 ]. The ELISA was validated according to the Food and Drug Administration’s ‘Guidance for Industry: Bioanalytical Method Validation’.…”

Section: Methodsmentioning

confidence: 99%

Increase of angiotensin II type 1 receptor auto-antibodies in Huntington’s disease

Lee

Heidecke²,

Schröder

et al. 2014

Mol Neurodegeneration

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BackgroundIn the recent years, a role of the immune system in Huntington’s disease (HD) is increasingly recognized. Here we investigate the presence of T cell activating auto-antibodies against angiotensin II type 1 receptors (AT1R) in all stages of the disease as compared to healthy controls and patients suffering from multiple sclerosis (MS) as a prototype neurologic autoimmune disease.ResultsAs compared to controls, MS patients show higher titers of anti-AT1R antibodies, especially in individuals with active disease. In HD, anti-AT1R antibodies are more frequent than in healthy controls or even MS and occur in 37.9% of patients with relevant titers ≥ 20 U/ml. In a correlation analysis with clinical parameters, the presence of AT1R antibodies in the sera of HD individuals inversely correlated with the age of onset and positively with the disease burden score as well as with smoking and infection.ConclusionsThese data suggest a dysfunction of the adaptive immune system in HD which may be triggered by different stimuli including autoimmune responses, infection and possibly also smoking.

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“…Diagnosis was confirmed by renal biopsy showing obliterative vasculopathy of arteries and arterioles in all cases ( Table S4 ). All healthy and SRC individuals were tested for the presence of AT 1 R and ET A R antibodies using a sandwich ELISA (CellTrend GmbH, Luckenwalde, Germany), as described in detail in [ 69 ]. Only SRC patients showed high (above 10 U/mL) AT 1 R- and ET A R-IgG levels.…”

Section: Methodsmentioning

confidence: 99%

Autoantibodies Targeting AT1- and ETA-Receptors Link Endothelial Proliferation and Coagulation via Ets-1 Transcription Factor

Catar

Herse-Naether

Zhu

et al. 2021

IJMS

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Scleroderma renal crisis (SRC) is an acute life-threatening manifestation of systemic sclerosis (SSc) caused by obliterative vasculopathy and thrombotic microangiopathy. Evidence suggests a pathogenic role of immunoglobulin G (IgG) targeting G-protein coupled receptors (GPCR). We therefore dissected SRC-associated vascular obliteration and investigated the specific effects of patient-derived IgG directed against angiotensin II type 1 (AT1R) and endothelin-1 type A receptors (ETAR) on downstream signaling events and endothelial cell proliferation. SRC-IgG triggered endothelial cell proliferation via activation of the mitogen-activated protein kinase (MAPK) pathway and subsequent activation of the E26 transformation-specific-1 transcription factor (Ets-1). Either AT1R or ETAR receptor inhibitors/shRNA abrogated endothelial proliferation, confirming receptor activation and Ets-1 signaling involvement. Binding of Ets-1 to the tissue factor (TF) promoter exclusively induced TF. In addition, TF inhibition prevented endothelial cell proliferation. Thus, our data revealed a thus far unknown link between SRC-IgG-induced intracellular signaling, endothelial cell proliferation and active coagulation in the context of obliterative vasculopathy and SRC. Patients’ autoantibodies and their molecular effectors represent new therapeutic targets to address severe vascular complications in SSc.

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The Detection of Antibodies to the Angiotensin II-Type 1 Receptor in Transplantation

Cited by 9 publications

References 5 publications

Anti-Angiotensin II Type 1 Receptor and Anti-Endothelial Cell Antibodies: A Cross-Sectional Analysis of Pathological Findings in Allograft Biopsies

Anti-Angiotensin II Type 1 Receptor and Anti-Endothelial Cell Antibodies: A Cross-Sectional Analysis of Pathological Findings in Allograft Biopsies

Increase of angiotensin II type 1 receptor auto-antibodies in Huntington’s disease

Autoantibodies Targeting AT1- and ETA-Receptors Link Endothelial Proliferation and Coagulation via Ets-1 Transcription Factor

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