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

• DOI: 10.1371/journal.pone.0152164
• Publication Date: 2016-03-23T18:13:25Z
• Authors: Richard B. Pouw; Mieke C. Brouwer; Judy Geissler; Laurens V. van He...; Sacha S. Zeerleder; Walter A. Wuillemin; Diana Wouters; Taco W. Kuijpers
• Keywords: 0301 basic medicine; 0303 health sciences; DNA Copy Number Variations; Science; Q; R; Antibodies, Monoclonal; Enzyme-Linked Immunosorbent Assay; Blood Proteins; Cross Reactions; 03 medical and health sciences; Complement Factor H; Sepsis; Medicine; Humans; Acute-Phase Reaction; Research Article

The major human complement regulator in blood, factor H (FH), has several closely related proteins, called FH-related (FHR) proteins. As all FHRs lack relevant regulatory activity, their physiological role is not well understood. FHR protein 3 (FHR-3) been suggested to compete with FH for binding Neisseria meningitidis, thereby affecting complement-mediated clearance. Clearly, the vivo outcome of such competition greatly depends on and FHR-3 concentrations. While levels have established, accurate were never unequivocally reported date. Moreover, CFHR3 gene copy numbers commonly vary, which may impact concentration. Hence, we generated five anti-FHR-3 mAbs specifically measure healthy donors determined number variation at CFH/CFHR locus. Finally, examined acute-phase response characteristics a small sepsis cohort. We mean 19 nM that under normal conditions correlates very large extent serum levels. On average, was 132-fold lower compared concentration same samples did behave as acute phase protein.