Figure 1.

(A) Kidney biopsies performed at 9 and 20 months postpresentation. Light microscopy (first row) shows mesangial hypercellularity, segmental endocapillary hypercellularity, and capillary wall double contours with marked capillary wall C3, C9, and CFHR5 seen on immunoperoxidase staining (second [C3] and fourth [C9, CFHR5] rows). On electron microscopy (third row), there were intramembranous and occasional subendothelial electron-dense deposits. Rare hump-like subepithelial deposits were seen in the first biopsy specimen. Rabbit anti-human C3 (Dako, www.dako.com), mouse anti-human C9 (Leica, www.leica.com), and mouse anti-human monoclonal CFHR5 antibodies (a gift from Dr J. McRae) were used for immunoperoxidase staining. (B) Serum complement C3 and creatinine levels versus time. Serum C3 levels remained profoundly depressed throughout the illness. Conversion factor for serum creatinine in mg/dL to μmol/L, ×88.4. (C) Family pedigree. II-3 (filled circle) denotes the index patient. A central dot within the symbol (circle and square denoting female and male individuals, respectively) indicates the sequence variant is present, empty symbols denote absence of the sequence variant, and symbols with a question mark indicate genetic status unknown. (D) Serum CFHR5 levels in individuals with biopsy-proven C3 glomerulonephritis and absence of the CFHR5 sequence variant. Median CFHR5 level in the C3 glomerulonephritis group (4.3; range 1.2-7.4 μg/mL; n = 23) was significantly lower (P = 0.02, Mann-Whitney test) than the median in healthy controls (5.5; range 3.4-10.1 μg/mL; n = 13). CFHR5 was measured by enzyme-linked immunosorbent assay using rabbit anti-human CFHR5 and mouse anti-human CFHR5 antibodies (both from Abcam, www.abcam.com) as capture and primary antibodies, respectively. The standard curve was generated using recombinant CFHR5 (R&D Systems, www.rndsystems.com).