Matthew Pickering1, H Terence Cook. 1. Centre for Complement & Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Abstract
PURPOSE OF REVIEW: There is an intimate association between complement dysregulation and glomerular pathology. Here we summarise the recent progress. RECENT FINDINGS: C3 glomerulopathy has been introduced as a term that encompasses glomerular pathology characterised by isolated C3 deposition. The prototypic example of C3 glomerulopathy is dense deposit disease (DDD). Characterisation of a mutant C3 molecule in familial DDD has reinforced the concept that this condition results from systemic C3 dysregulation. Complement factor H-related 5 (CFHR5) nephropathy is the most recently described C3 glomerulopathy. Its characterisation supports a biological role for CFHR5 on complement regulation within the kidney. Atypical haemolytic uraemic syndrome (aHUS) is strongly associated with genetic defects in complement regulation. Animal model data indicate that the critical step in the development of renal thrombotic microangiopathy in this syndrome is activation of complement C5. Importantly, there are now many reports of the successful use of a monoclonal anti-C5 antibody therapy (eculizumab) in this syndrome and clinical trials are in progress. Intriguingly, animal model data have demonstrated a critical role for C5 activation in pauci-immune glomerulonephritis. SUMMARY: C5 inhibition appears to be effective therapy for aHUS. An important unresolved question is the role of C5 inhibition in C3 glomerulopathies.
PURPOSE OF REVIEW: There is an intimate association between complement dysregulation and glomerular pathology. Here we summarise the recent progress. RECENT FINDINGS:C3 glomerulopathy has been introduced as a term that encompasses glomerular pathology characterised by isolated C3 deposition. The prototypic example of C3 glomerulopathy is dense deposit disease (DDD). Characterisation of a mutant C3 molecule in familial DDD has reinforced the concept that this condition results from systemic C3 dysregulation. Complement factor H-related 5 (CFHR5) nephropathy is the most recently described C3 glomerulopathy. Its characterisation supports a biological role for CFHR5 on complement regulation within the kidney. Atypical haemolytic uraemic syndrome (aHUS) is strongly associated with genetic defects in complement regulation. Animal model data indicate that the critical step in the development of renal thrombotic microangiopathy in this syndrome is activation of complement C5. Importantly, there are now many reports of the successful use of a monoclonal anti-C5 antibody therapy (eculizumab) in this syndrome and clinical trials are in progress. Intriguingly, animal model data have demonstrated a critical role for C5 activation in pauci-immune glomerulonephritis. SUMMARY: C5 inhibition appears to be effective therapy for aHUS. An important unresolved question is the role of C5 inhibition in C3 glomerulopathies.
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