CFH

Background

Complement factor H (CFH) is an essential regulator for normal complement activity, which negatively inhibits the alternative pathway and complement amplification. CFH is a large plasma protein encoded by the CFH gene. Human CFH is a 155 kDa heavily glycoprotein composed of 20 complement control protein (CCP) domains (or short consensus repeats), each of which consists of around 60 amino acids with 2 disulfides (CysI-CysIII and CysII-CysIV). The adjacent domains are connected by three to eight residues. The N-terminal CCP1-4 are responsible for the binding to C3b and also act as a cofactor for complement factor I to catalyze C3b proteolysis. The CCP7 and C-terminal CCP19-20 contain binding sites for C3b, C3d, sialic acid, and glycosaminoglycans, which are responsible for anchoring CFH to the host surface.

1. When binds to glycosaminoglycans and or sialic acids on host cells, CFH acts as a soluble inhibitor to prevent complement activation on host cell surfaces.
2. CFH functions as a cofactor for complement factor I to regulate proteolytic degradation of already-deposited C3b.
3. CFH accelerate the decay of C3 convertase C3bBb in the complement alternative pathway, thereby decreasing or inhibiting the formation of C3b.
4. CFH also mediates multiple cellular responses through binding to specific receptors, such as complement receptor 3.

The abnormal expression or mutations of CFH directly cause complement dysfunctions, leading to various disorders, including autoimmune diseases, age-related macular degeneration, atypical hemolytic uremic syndrome, schizophrenia, and increased susceptibility to infections.

Fig.1 The structure of CFH. Distributed under CC BY-SA 4.0, from Wiki, without modification.

CFH Functional Service

Creative Biolabs provides high-quality CFH proteins, antibodies, and ELISA kits. We also offer CFH-related functional assays, enabling precise monitoring of CFH-related pathways and complement system regulation.

CFH functional tests play a key role in exploring how CFH regulates immune responses and contributes to the development of different diseases. Our anti-CFH aptamers are used in assays to assess CFH activity, binding capacity, and interaction with other complement components. These tests are vital for investigating CFH-related disorders.

Fig.2 Binding of CFH variants to C3b using surface plasmon resonance.¹

In one study, functional testing revealed impaired CFH binding in patients with a specific genetic mutation, contributing to enhanced complement activation. This discovery provided insights into targeted therapeutic approaches for CFH-related diseases. In another study, functional characterization of 105 aHUS-associated CFH variants successfully classified all CFH variants and fully documented their pathogenicity, thereby accurately interpreting CFH variants and helping to personalize and optimize clinical care for aHUS patients. The importance of CFH functional tests lies in their ability to identify abnormalities in complement regulation and facilitate personalized treatment strategies.

Creative Biolabs provides CFH-functional services, including customized functional assays, affinity measurements, and interaction studies. Our services help clients accelerate research by delivering accurate data and expert analysis, ensuring high-quality, reliable results for your projects.

Click the following targets to view our CFH-related product lists.

Reference

1. Wong, Edwin KS, et al. "Functional characterization of rare genetic variants in the N-terminus of complement factor H in aHUS, C3G, and AMD." Frontiers in immunology 11 (2021): 602284. Distributed under Open Access license CC BY 4.0, without modification.