Creative Biolabs has more than ten years' experience in antibody research and production, and is committed to providing one-stop services for scientific research institutions and pharmaceutical companies. In particular, we provide custom production services for the production of agonistic autoantibodies, which will contribute to the treatment of autoimmune diseases.

Introduction of Agonistic Autoantibody

A defining characteristic of autoimmune diseases is the presence of autoantibodies or self-activated T cells directed against autoantigens present on the target cells. Many autoimmune diseases are caused by the presence of autoantibodies that bind to G protein-coupled receptors (GPCRs) on the cell surface. Relatively common to these diseases are, for example, type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, Graves' disease, myasthenia gravis and rheumatoid arthritis. Currently, agonistic autoantibodies against G protein-coupled receptors have been observed in many cardiovascular disease states, such as representative systemic sclerosis (SSc), which is characterized by microvascular disease, excessive fibrosis and some circulating autoantibodies to cells and extracellular components. Rapidly emerging evidence suggests that receptor-activated autoantibodies contribute to disease, and efforts to detect and remove these pathogenic autoantibodies or block their effects will provide promising therapeutic possibilities.

Fig.1 Cardiovascular receptor-agonistic autoantibodies contribute to cardiovascular disease. (Xia, 2011)

Custom Agonistic Autoantibody Development Service in Creative Biolabs

Based on advanced antibody engineering and phage display technology service platforms, Creative Biolabs provides flexible customized solutions according to the special needs of customers, aiming at providing high-quality antibodies for customers. In the production of agonistic autoantibodies, we are currently involved in:

• Custom Anti-Endothelial Cells (AECA) Antibody

Anti-AECA antibodies are a family of heterologous antibodies that react with endothelial cell antigens. These antibodies are present in various diseases and recognize several antigenic determinants. Different pathophysiological effects of AECA, including direct or indirect cytotoxicity and endothelial cell apoptosis, were observed in in vitro experiments, and some AECA activated endothelial cells, resulting in increased leukocyte adhesion, coagulation activation, and vascular thrombosis. Therefore, anti-AECA antibodies play an important role in combating these AECA-mediated diseases.

• Custom Anti-Platelet-derived Growth Factor Receptor (PDGFR) Antibody

PDGFR is a 170-185 kDa transmembrane glycoprotein that mediates cell type activation and plays a fundamental role in the pathogenesis of SSc such as fibroblasts and smooth muscle cells. Phosphorylation of tyrosine residues in activated PDGFRs can control actin recombination, transcription, cell growth, migration and differentiation, and lead to activation of Ras, Raf and extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathways. Recently, it has been confirmed that anti-PDGFR autoantibody can induce the proliferation and migration of human pulmonary vascular smooth muscle cells in vitro. This is an important finding that further confirms the activation of these autoantibodies and their contribution to the pathogenesis of SSc, and may contribute to SSc-related diseases such as pulmonary hypertension (PAH).

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

AT1R is the most typical angiotensin receptor, which is widely expressed in vascular system cells and immune cells. It has pressure effect and regulates aldosterone secretion. It is an important effector of controlling blood pressure and volume in cardiovascular system. AT1R autoantibodies are known to be associated with malignant hypertension, preeclampsia and vascular rejection in kidney transplantation. They are also suspected of being pathogenic to vascular lesions in SSc. Subsequently, many studies have shown that anti-AT1R autoantibodies stimulate AT1R of various cell types and induce biological reactions related to pathophysiology of vascular diseases, which are important targets for the treatment of related diseases.

• Custom Anti-Endothelin-1 Type A Receptor (ETaR) Antibody

Endothelin-1 (ET-1), a member of the GPCR family, is a potent endogenous vasoconstrictor, mainly secreted by endothelial cells. It acts through two types of receptors: ETa and ETb. Studies have shown that ETaR autoantibodies aggravate right ventricular hypertrophy and vascular remodeling in vivo, promote the proliferation of vascular smooth muscle cells (SMC) and destroy the endothelial barrier. In addition to being detected in patients with SSc, ETaR autoantibodies up-regulate the expression of related markers of pulmonary hypertension (PAH) associated with systemic lupus erythematosus (SLE). This autoantibody plays a biological role in inducing the phosphorylation of signal-regulated kinase 1/2 in endothelial cells and increasing the expression of transforming growth factor beta gene, which may be blocked by specific receptor antagonists.

Features of Our Services

• Efficient phage display platform, recombinant protein expression and purification technology, promote high success rate of antigen expression.
• Customized immunization, screening and testing can be provided according to the final application requirements of customers.
• ELISA, WB, IHC, FACS and other validation platforms, multi-cell and multi-tissue validation are designed to improve the success rate of antibody screening with low background and high sensitivity.
• Quote price step by step, charge by node, reduce customer risk and save cost.

If you are interested in our custom agonistic autoantibody development service, please feel free to contact us.

Reference

1. Yang, X.; Kellems, R. E. Receptor-activating autoantibodies and disease: preeclampsia and beyond. Expert Review of Clinical Immunology. 2011, 7 (5): 659-674.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.