FHR-4, Human, mAb clone 4A.8

Clone 4A.8 recognizes human full-length Complement Factor H-related protein 4 (FHR-4). FHR-4 is a glycoprotein that is part of the complement regulatory protein family. It is synthesized and secreted primarily by the liver, as well as immune cells such as monocytes, macrophages, and dendritic cells. Unique among the FHR proteins, FHR-4 has two splice variants: FHR-4A, a longer protein with an approximate molecular weight of 86 kDa composed of 9 short consensus repeats (SCR) domains, and FHR-4B, a shorter protein of around 42 kDa with 5 SCR domains. HM2438 is an antibody that recognizes both variants, FHR-4A and FHR-4B.

Structurally, FHR-4 shares homology with Complement Factor H (CFH), a key regulator within the complement system. FHR-4 operates within the complement regulatory network, particularly affecting the alternative pathway (AP) of the complement system. It binds C3b, thereby participating in the regulation of AP activation. FHR-4 also plays a role in the opsonization of necrotic cells, facilitating the binding and recruitment of CRP.

Elevated systemic levels of FHR-4 have been strongly associated with age-related macular degeneration (AMD). However, studies have also reported inconclusive or contradictory results regarding the involvement of FHR-4 in AMD. This ambiguity highlights the need for further research to clarify FHR-4’s role in AMD and potentially other diseases. FHR-4’s unique structural properties and its diverse biological functions emphasize its significance in the complement system and its potential as a target for therapeutic interventions.