TY - JOUR
T1 - Where next with atypical hemolytic uremic syndrome?
AU - Jokiranta, T. Sakari
AU - Zipfel, Peter F.
AU - Fremeaux-Bacchi, Veronique
AU - Taylor, C. Mark
AU - Goodship, Timothy J H
AU - Noris, Marina
PY - 2007/9
Y1 - 2007/9
N2 - Hemolytic uremic syndrome (HUS) is a systemic disease characterized by damage to endothelial cells, erythrocytes and kidney glomeruli. A "typical" form of HUS follows gastrointestinal infection with enterohemorrhagic E. coli (e.g. O157:H7). Atypical HUS (aHUS) is not associated with gastrointestinal infections but is sporadic or familial in nature. Approximately 50% of aHUS cases are associated with a mutation in one or more genes coding for proteins involved in regulation or activation of the alternative pathway of complement. The link between the disease and the mutations shows the important balance of the alternative pathway between activation and regulation on host cell surfaces. It also demonstrates the power of this pathway in destroying cellular targets in general. In this review we discuss the current knowledge on pathogenesis, classification, diagnostics and management of this disease. We indicate a comprehensive diagnostic approach for aHUS based on the latest knowledge on complement dysregulation to gain both immediate and future patient benefit by assisting in choosing more appropriate therapy for each patient. We also indicate directions in which therapy of aHUS might improve and indicate the need to re-think the terminology and categorisation of the HUS-like diseases so that any advantage in the understanding of complement regulatory problems can be applied to patients accurately.
AB - Hemolytic uremic syndrome (HUS) is a systemic disease characterized by damage to endothelial cells, erythrocytes and kidney glomeruli. A "typical" form of HUS follows gastrointestinal infection with enterohemorrhagic E. coli (e.g. O157:H7). Atypical HUS (aHUS) is not associated with gastrointestinal infections but is sporadic or familial in nature. Approximately 50% of aHUS cases are associated with a mutation in one or more genes coding for proteins involved in regulation or activation of the alternative pathway of complement. The link between the disease and the mutations shows the important balance of the alternative pathway between activation and regulation on host cell surfaces. It also demonstrates the power of this pathway in destroying cellular targets in general. In this review we discuss the current knowledge on pathogenesis, classification, diagnostics and management of this disease. We indicate a comprehensive diagnostic approach for aHUS based on the latest knowledge on complement dysregulation to gain both immediate and future patient benefit by assisting in choosing more appropriate therapy for each patient. We also indicate directions in which therapy of aHUS might improve and indicate the need to re-think the terminology and categorisation of the HUS-like diseases so that any advantage in the understanding of complement regulatory problems can be applied to patients accurately.
KW - Complement
KW - Hemolytic uremic syndrome
KW - Human disease
KW - Innate immunity
KW - Thrombotic microangiopathy
KW - TMA
UR - http://www.scopus.com/inward/record.url?scp=34548358982&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548358982&partnerID=8YFLogxK
U2 - 10.1016/j.molimm.2007.06.003
DO - 10.1016/j.molimm.2007.06.003
M3 - Article
C2 - 17768107
AN - SCOPUS:34548358982
VL - 44
SP - 3889
EP - 3900
JO - Molecular Immunology
JF - Molecular Immunology
SN - 0161-5890
IS - 16
ER -