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An engineered construct combining complement regulatory and surface-recognition domains represents a minimal-size functional Factor H

Hebecker, M. and Alba-Domínguez, M. and Roumenina, L.T. and Reuter, S. and Hyvärinen, S. and Józsi, Mihály (2013) An engineered construct combining complement regulatory and surface-recognition domains represents a minimal-size functional Factor H. JOURNAL OF IMMUNOLOGY, 191 (2). pp. 912-921. ISSN 0022-1767

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Abstract

Complement is an essential humoral component of innate immunity; however, its inappropriate activation leads to pathology. Polymorphisms, mutations, and autoantibodies affecting factor H (FH), a major regulator of the alternative complement pathway, are associated with various diseases, including age-related macular degeneration, atypical hemolytic uremic syndrome, and C3 glomerulopathies. Restoring FH function could be a treatment option for such pathologies. In this article, we report on an engineered FH construct that directly combines the two major functional regions of FH: the N-terminal complement regulatory domains and the C-terminal surface-recognition domains. This minimal-size FH (mini-FH) binds C3b and has complement regulatory functions similar to those of the full-length protein. In addition, we demonstrate that mini-FH binds to the FH ligands C-reactive protein, pentraxin 3, and malondialdehyde epitopes. Mini-FH was functionally active when bound to the extracellular matrix and endothelial cells in vitro, and it inhibited C3 deposition on the cells. Furthermore, mini-FH efficiently inhibited complement-mediated lysis of host-like cells caused by a disease-associated FH mutation or by anti-FH autoantibodies. Therefore, mini-FH could potentially be used as a complement inhibitor targeting host surfaces, as well as to replace compromised FH in diseases associated with FH dysfunction

Item Type: Article
Additional Information: Published online before print June 14, 2013
Subjects: R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 05 Feb 2014 15:30
Last Modified: 10 Jun 2016 12:21
URI: http://real.mtak.hu/id/eprint/9808

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