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Complement Factor H-Related Protein 3 Serum Levels Are Low Compared to Factor H and Mainly Determined by Gene Copy Number Variation in CFHR3

Pouw, Richard B. and Brouwer, Mieke C. and Geissler, Judy and van Herpen, Laurens V. and Zeerleder, Sacha S. and Wuillemin, Walter A. and Wouters, Diana and Kuijpers, Taco W.. (2016) Complement Factor H-Related Protein 3 Serum Levels Are Low Compared to Factor H and Mainly Determined by Gene Copy Number Variation in CFHR3. PLoS ONE, 11 (3). e0152164.

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Abstract

The major human complement regulator in blood, complement factor H (FH), has several closely related proteins, called FH-related (FHR) proteins. As all FHRs lack relevant complement regulatory activity, their physiological role is not well understood. FHR protein 3 (FHR-3) has been suggested to compete with FH for binding to Neisseria meningitidis, thereby affecting complement-mediated clearance. Clearly, the in vivo outcome of such competition greatly depends on the FH and FHR-3 concentrations. While FH levels have been established, accurate FHR-3 levels were never unequivocally reported to date. Moreover, CFHR3 gene copy numbers commonly vary, which may impact the FHR-3 concentration. Hence, we generated five anti-FHR-3 mAbs to specifically measure FHR-3 in human healthy donors of which we determined the gene copy number variation at the CFH/CFHR locus. Finally, we examined the acute-phase response characteristics of FHR-3 in a small sepsis cohort. We determined FHR-3 levels to have a mean of 19 nM and that under normal conditions the copy number of CFHR3 correlates to a very large extent with the FHR-3 serum levels. On average, FHR-3 was 132-fold lower compared to the FH concentration in the same serum samples and FHR-3 did not behave as a major acute phase response protein.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molekulare Pharmazie (Ricklin)
UniBasel Contributors:Pouw, Richard Benjamin
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
ISSN:1932-6203
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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edoc DOI:
Last Modified:10 May 2019 14:24
Deposited On:10 May 2019 14:24

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