Diverse Responses of Autoantibodies to the Angiotensin II Type 1 Receptor in Primary Aldosteronism.

Primary aldosteronism is a common form of endocrine hypertension mainly caused by a unilateral aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia (BAH). AT1R-Abs (autoantibodies to the angiotensin II type 1 receptor) have been reported in patients with disorders associated with hypertension. Our objective was to assess AT1R-Ab levels in patients with primary aldosteronism (APA, n=40 and BAH, n=40) relative to patients with primary hypertension (n=40), preeclampsia (n=23), and normotensive individuals (n=25).

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

Background: This 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).

Methods: Non-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.

Non-HLA antibodies against endothelial targets bridging allo- and autoimmunity.

Detrimental actions of donor-specific antibodies (DSAs) directed against both major histocompatibility antigens (human leukocyte antigen [HLA]) and specific non-HLA antigens expressed on the allograft endothelium are a flourishing research area in kidney transplantation. Newly developed solid-phase assays enabling detection of functional non-HLA antibodies targeting G protein-coupled receptors such as angiotensin type I receptor and endothelin type A receptor were instrumental in providing long-awaited confirmation of their broad clinical relevance. Numerous recent clinical studies implicate angiotensin type I receptor and endothelin type A receptor antibodies as prognostic biomarkers for earlier occurrence and severity of acute and chronic immunologic complications in solid organ transplantation, stem cell transplantation, and systemic autoimmune vascular disease.

Non-HLA antibodies in solid organ transplantation: recent concepts and clinical relevance.

Purpose Of Review: Humoral responses beyond major histocompatibility antigens continue to receive the attention of the transplantation community. We report on clinical studies testing clinical relevance of non-human leukocyte antigen (HLA) antigens in solid organ transplantation and provide an update on novel experimental findings. A conceptual framework on the role of graft microenvironment during initiation of non-HLA-related humoral immunity is addressed as well.

Non-HLA-antibodies targeting Angiotensin type 1 receptor and antibody mediated rejection.

Antibody-mediated mechanisms directed against non-HLA related targets may exert negative impact on allograft function and survival. Angiotensin type 1 receptor (AT(1)R) emerges as a functional target for non-HLA allo- and autoantibodies (AT(1)R-Abs) comprising of IgG1 and IgG3 subclasses. Proof of concept for pathophysiologic relevance of AT(1)R-Abs in antibody mediated rejection (AMR) in renal transplants was provided by passive transfer studies in animal model and therapeutic rescue of patients.

Role of non-HLA antibodies in organ transplantation.

Purpose Of Review: Humoral responses beyond major histocompatibility antigens receive an increased attention of the transplantation community. We aimed to summarize the data on discovery of new antigenic targets, novel experimental findings, recent diagnostic developments, and introduction of new technologies in the field of non-HLA antigens in solid organ transplantation.

Recent Findings: Non-HLA antibodies can be currently reliably detected by solid-phase assays (MICA, angiotensin type 1 receptor, collagen-V, vimentin), immunofluorescence (antibodies against antigens expressed on umbilical vein endothelial cells), or flow-crossmatch techniques (antibodies against donor endothelial progenitors).