Custom Anti-Angiotensin II Type 1 Receptor (AT1R) Antibody Service

Antibodies against G-protein coupled receptors (GPCR), angiotensin II type 1 receptor (AT1R), are among a growing number of autoantibodies which are found to be correlated with allograft dysfunction. These antibodies have also been shown to activate their target receptors and affect signaling pathways. With an extensive reputation in the antibody field, Creative Biolabs taps into our popular agonistic antibody development technologies to generate a wide range of high-quality antibodies, including AT1R antibodies. And we provide custom services to help clients design, qualify, and manufacture a variety of specific agonistic autoantibodies for the use of preclinical research and clinical applications.

AT1R Introduction

AT1R is a seven-transmembrane GPCR that mediates the majority of pathophysiologic actions of the endogenous ligand, angiotensin II, including arterial blood pressure and water-salt balance. Numerous contexts are attributed to over-activity of this angiotensin II-AT1R interaction, such as hypertension and vascular remodeling. The human gene for AT1R, mapped at chromosome 3, encodes four classes of exons. The alternative splicing of exons 1, 2, 3 resulting in the entire coding region of exon 4, generates four major transcripts with greatly different translating rates. This mRNA processing induces a diversity of AT1R expression levels. There are some polymorphisms of AT1R, but the most studied is A1166C, associated with improved responsiveness to angiotensin II, cardiovascular, and renal pathologies.

Fig.1 AT1R antibody (AT1Rab). (Philogene, 2019)

Custom Anti-AT1R Antibody Services at Creative Biolabs

It is known that antibodies to AT1R have been involved in several vascular pathologies. In renal transplantation, increased levels of anti-AT1R antibodies are connected with antibody-mediated rejection in the absence of donor human leukocyte antigen (HLA) specific antibodies. In heart transplantation, evaluated levels of anti-AT1R antibodies are associated with cell and antibody-mediated rejection, along with an early onset of microvasculopathy. Notably, Creative Biolabs always focuses on the current investigations regarding the effects of anti-AT1R antibodies in organ transplantation and has summarized their roles in different pathological responses.

• Role of anti-AT1R antibodies in renal transplantation -- A synergistic influence of high titered AT1R antibody and HLA class II donor antigen antibody has been supposed to contribute to the kidney transplant rejection and hypertensive encephalopathy.
• Role of anti-AT1R antibodies in thoracic transplantation -- A raising in the expression of AT1R may bring about boosting the efficacy of angiotensin II, thereby promoting the pathogenesis of transplant vasculopathy.
• Role of anti-AT1R antibodies in vascular injury -- The transplant process itself might increase the expression of AT1R thus exacerbating the impact of antibody to the receptor on the activated vascular cells. Ischemia and reperfusion injury could cause oxidative stress triggering alloantigen immune responses.

Anti-AT1R antibodies are coupled to the second extracellular loop of the AT1R. There are multiple pathways by which these antibodies may appear directed at AT1R including both autoreactivity and alloreactive behaviors. Protein antigenic determinants possibly become accessible after injury or through transplantation itself. The inflammatory event is likely to lead to de novo expression of these autoantigens. Here, our experts are committed to working with global customers on agonistic autoantibody research and development, with proven platforms and advanced technologies. Especially, we provide optimized custom Anti- AT1R antibody services that meet process monitoring, characteristic testing, and other specific needs.

Fig.2 Non-HLA agonistic anti-AT1R antibodies induce a distinctive phenotype of antibody-mediated rejection in kidney transplantation. (Lefaucheur, 2019)

Highlights

• End-to-end solutions from design, development, to final delivery
• Cost-effective, time-saving schemes
• Expertise in the pathophysiologic mechanism of agonistic autoantibodies
• Years of experience in the agonist antibody generation

All together, assessing the AT1R antibody status with HLA profile can help to determine the comprehensive immunologic risk for transplant recipients. As a first-class service provider in the world, Creative Biolabs offers reliable qualification of customized anti-AT1R antibodies to meet regulatory requirements, as well as state-of-the-art orthogonal methods, including but not limited to antibody affinity extraction, antibody affinity maturation, and antibody humanization. Meanwhile, we’re also skilled at developing many other types of therapeutic antibodies for academic studies or clinical trials. For more information, please feel free to contact us.

Reference

1. Philogene, M.C.; et al. Antibodies against angiotensin II Type 1 and endothelin A receptors: relevance and pathogenicity. Hum Immunol. 2019.
2. Lefaucheur, C.; et al. Non-HLA agonistic anti-angiotensin II type 1 receptor antibodies induce a distinctive phenotype of antibody-mediated rejection in kidney transplant recipients. Kidney Int. 2019, 96(1): 189-201.

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