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. 2016 Mar 23;11(3):e0152164. doi: 10.1371/journal.pone.0152164. eCollection 2016.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Reaction / blood
  • Acute-Phase Reaction / immunology
  • Antibodies, Monoclonal / immunology
  • Blood Proteins / analysis
  • Blood Proteins / genetics*
  • Blood Proteins / immunology
  • Complement Factor H / analysis
  • Complement Factor H / genetics*
  • Cross Reactions
  • DNA Copy Number Variations
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Sepsis / blood
  • Sepsis / immunology


  • Antibodies, Monoclonal
  • Blood Proteins
  • CFHR3 protein, human
  • Complement Factor H

Grants and funding

Research leading to these results has received funding from the European Union’s seventh Framework program under EC-GA no. 279185 (EUCLIDS; The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.