Complement regulatory genes and hemolytic uremic syndromes

被引:124
作者
Kavanagh, David [1 ]
Richards, Anna [1 ]
Atkinson, John [1 ]
机构
[1] Washington Univ, Sch Med, Dept Med, Div Rheumatol, St Louis, MO 63130 USA
来源
ANNUAL REVIEW OF MEDICINE | 2008年 / 59卷
关键词
factor H (FH); membrane cofactor protein (MCP; CD46); factor I (FI); factor B (FB); complement C3 (C3); transplantation;
D O I
10.1146/annurev.med.59.060106.185110
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Hemolytic uremic syndrome is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. It is one of a group of conditions termed the thrombotic microangiopathics, which are characterized by prominent endothelial cell injury. It may be diarrheal-associated or atypical (aHUS). Evidence for a pathogenic role of the alternative pathway of complement was first suggested in 1974. Mutations in the complement regulatory proteins factor H, membrane cofactor protein (CD46), and factor I predispose to aHUS development. Mutations of the activating components factor B and complement C3 have also been reported. Penetrance is similar to 50%, suggesting other genetic and environmental modifiers are needed for disease expression. Identification of mutations is important owing to differences in mortality, renal survival, and outcome of renal transplantation. Current treatment is plasma infusion/exchange, but complement inhibitor therapy provides hope for the future.
引用
收藏
页码:293 / 309
页数:17
相关论文
共 73 条
[41]   Screening for complement system abnormalities in patients with atypical hemolytic uremic syndrome [J].
Kavanagh, David ;
Richards, Anna ;
Fremeaux-Bacchi, Veronique ;
Noris, Marina ;
Goodship, Timothy ;
Remuzzi, Giuseppe ;
Atkinson, John P. .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2007, 2 (03) :591-596
[42]   Atypical haemolytic uraemic syndrome [J].
Kavanagh, David ;
Goodship, Timothy H. J. ;
Richards, Anna .
BRITISH MEDICAL BULLETIN, 2006, 77-78 :5-22
[43]  
KIM Y, 1977, J LAB CLIN MED, V89, P845
[44]   Modeling how CD46 deficiency predisposes to atypical hemolytic uremic syndrome [J].
Liszewski, M. Kathryn ;
Leung, Marilyn K. ;
Schraml, Barbara ;
Goodship, Timothy H. J. ;
Atkinson, John P. .
MOLECULAR IMMUNOLOGY, 2007, 44 (07) :1559-1568
[45]   Genomic disorders: Molecular mechanisms for rearrangements and conveyed phenotypes [J].
Lupski, JR ;
Stankiewicz, P .
PLOS GENETICS, 2005, 1 (06) :627-633
[46]   Complement factor H: sequence analysis of 221 kb of human genomic DNA containing the entire fH, fHR-1 and fHR-3 genes [J].
Male, DA ;
Ormsby, RJ ;
Ranganathan, S ;
Giannakis, E ;
Gordon, DL .
MOLECULAR IMMUNOLOGY, 2000, 37 (1-2) :41-52
[47]   Human factor H-related protein 5 has cofactor activity, inhibits C3 convertase activity, binds heparin and C-reactive protein, and associates with lipoprotein [J].
McRae, JL ;
Duthy, TG ;
Griggs, KM ;
Ormsby, RJ ;
Cowan, PJ ;
Cromer, BA ;
McKinstry, WJ ;
Parker, MW ;
Murphy, BF ;
Gordon, DL .
JOURNAL OF IMMUNOLOGY, 2005, 174 (10) :6250-6256
[48]   Mechanisms of disease - Thrombotic microangiopathies [J].
Moake, JL .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 347 (08) :589-600
[49]  
MONTEFERRANTE G, 2007, MOL IMMUNOL, V44, P1074
[50]   Shigatoxin triggers thrombotic thrombocytopenic purpura in genetically susceptible ADAMTS13-deficient mice [J].
Motto, DG ;
Chauhan, AK ;
Zhu, GJ ;
Homeister, J ;
Lamb, CB ;
Desch, KC ;
Zhang, WR ;
Tsai, HM ;
Wagner, DD ;
Ginsburg, D .
JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (10) :2752-2761