Furthermore, the mutant protein has been shown to have reduced affinity for glomerular-bound complement, raising the possibility of impaired targeting to complement within the kidney (3).
Its identification suggests a role for the CFHR5 protein in the regulation of complement in the kidney.
The biological role of CFHR5 is unclear, but it is postulated to have a physiologic role in the processing of complement within the kidney.
CFHR5 has been shown to have complement-regulatory function in vitro and to colocalize with complement deposits within the kidney in a variety of glomerular pathologic states.
Although the role of CFHR5 is not yet fully understood, its complement regulatory activity in vitro (4) and co-localization with renal complement deposits in vivo (5) suggest that it may play a role in complement regulation within the kidney.
Thus, it is generally accepted that aHUS is a disease of excessive complement activation in the kidney glomerular and arteriolar cells.
Additionally and in contrast to our previous results, we found a persistent complement activation in the kidney of BD rats treated with prednisolone treatment.
Slow progression, minimal urine proteinuria without active sediment, bilateral small echogenic kidneys on ultrasound examination and negative immunofluorescence for IgG, IgM, and complement-3 in the kidney biopsy are strongly in favor of a tubulo-interstitial disease with a toxic etiology [ 10].
These include vascular disease of the kidney, complement activation on arterioles [ 12, 13], coagulopathy [ 14], venocalyceal fistula [ 15], abnormal ureteral peristalsis [ 16], hypersensitivity [ 12], psychopathology [ 17, 18], intratubular deposition of calcium [ 2, 15, 19, 20] and nephritis [ 16, 17].
The complex role of STAT4 in vivo is illustrated by the observation that STAT4-deficient lupus mice have aggravated nephritis and increased mortality, despite the fact that they have decreased autoantibody levels and complement depositions in the kidneys (27).
