Schäfer, Nicole; Grosche, Antje; Reinders, Joerg; Hauck, Stefanie M; Pouw, Richard B; Kuijpers, Taco W; Wouters, Diana; Ehrenstein, Boris; Enzmann, Volker; Zipfel, Peter F; Skerka, Christine; Pauly, Diana (2016). Complement Regulator FHR-3 Is Elevated either Locally or Systemically in a Selection of Autoimmune Diseases. Frontiers in immunology, 7(542), p. 542. Frontiers Research Foundation 10.3389/fimmu.2016.00542
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The human complement factor H-related protein-3 (FHR-3) is a soluble regulator of the complement system. Homozygous cfhr3/1 deletion is a genetic risk factor for the autoimmune form of atypical hemolytic-uremic syndrome (aHUS), while also found to be protective in age-related macular degeneration (AMD). The precise function of FHR-3 remains to be fully characterized. We generated four mouse monoclonal antibodies (mAbs) for FHR-3 (RETC) without cross-reactivity to the complement factor H (FH)-family. These antibodies detected FHR-3 from human serum with a mean concentration of 1 μg/mL. FHR-3 levels in patients were significantly increased in sera from systemic lupus erythematosus, rheumatoid arthritis, and polymyalgia rheumatica but remained almost unchanged in samples from AMD or aHUS patients. Moreover, by immunostaining of an aged human donor retina, we discovered a local FHR-3 production by microglia/macrophages. The mAb RETC-2 modulated FHR-3 binding to C3b but not the binding of FHR-3 to heparin. Interestingly, FHR-3 competed with FH for binding C3b and the mAb RETC-2 reduced the interaction of FHR-3 and C3b, resulting in increased FH binding. Our results unveil a previously unknown systemic involvement of FHR-3 in rheumatoid diseases and a putative local role of FHR-3 mediated by microglia/macrophages in the damaged retina. We conclude that the local FHR-3/FH equilibrium in AMD is a potential therapeutic target, which can be modulated by our specific mAb RETC-2.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Augenklinik > Forschungsgruppe Augenheilkunde |
UniBE Contributor: |
Enzmann, Volker |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1664-3224 |
Publisher: |
Frontiers Research Foundation |
Language: |
English |
Submitter: |
Volker Enzmann |
Date Deposited: |
26 May 2017 15:34 |
Last Modified: |
05 Dec 2022 15:03 |
Publisher DOI: |
10.3389/fimmu.2016.00542 |
PubMed ID: |
27965669 |
Uncontrolled Keywords: |
FH competition; FHR-3/CFHR3; immune therapy; microglia/macrophage; retinal degeneration; rheumatic disease; specific antibody |
BORIS DOI: |
10.7892/boris.96260 |
URI: |
https://boris.unibe.ch/id/eprint/96260 |
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