Document Detail


Antibody therapy in the management of shiga toxin-induced hemolytic uremic syndrome.
MedLine Citation:
PMID:  15489355     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hemolytic uremic syndrome (HUS) is a disease that can lead to acute renal failure and often to other serious sequelae, including death. The majority of cases are attributed to infections with Escherichia coli, serotype O157:H7 strains in particular, which cause bloody diarrhea and liberate one or two toxins known as Shiga toxins 1 and 2. These toxins are thought to directly be responsible for the manifestations of HUS. Currently, supportive nonspecific treatment is the only available option for the management of individuals presenting with HUS. The benefit of antimicrobial therapy remains uncertain because of several reports which claim that such intervention can in fact exacerbate the syndrome. There have been only a few specific therapies directed against neutralizing the activities of these toxins, but none so far has been shown to be effective. This article reviews the literature on the mechanism of action of these toxins and the clinical manifestations and current management and treatment of HUS. The major focus of the article, however, is the development and rationale for using neutralizing human antibodies to combat this toxin-induced disease. Several groups are currently pursuing this approach with either humanized, chimeric, or human antitoxin antibodies produced in transgenic mice. They are at different phases of development, ranging from preclinical evaluation to human clinical trials. The information available from preclinical studies indicates that neutralizing specific antibodies directed against the A subunit of the toxin can be highly protective. Such antibodies, even when administered well after exposure to bacterial infection and onset of diarrhea, can prevent the occurrence of systemic complications.
Authors:
Saul Tzipori; Abhineet Sheoran; Donna Akiyoshi; Arthur Donohue-Rolfe; Howard Trachtman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  Clinical microbiology reviews     Volume:  17     ISSN:  0893-8512     ISO Abbreviation:  Clin. Microbiol. Rev.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-10-18     Completed Date:  2005-01-10     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  8807282     Medline TA:  Clin Microbiol Rev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  926-41, table of contents     Citation Subset:  IM    
Affiliation:
Division of Infectious Diseases, Tufts University School of Veterinary Medicine, 200 Westborough Rd., North Grafton, MA 01536, USA. Saul.tzipori@tufts.edu.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Bacterial / administration & dosage*,  immunology,  therapeutic use
Antibodies, Monoclonal / immunology,  therapeutic use*
Antibody Specificity
Disease Models, Animal
Hemolytic-Uremic Syndrome / chemically induced,  immunology,  therapy*
Humans
Immunization, Passive* / methods
Shiga Toxin 2 / immunology*,  toxicity
Shigella dysenteriae / chemistry,  immunology*
Grant Support
ID/Acronym/Agency:
DK52147/DK/NIDDK NIH HHS; R01 AI41326/AI/NIAID NIH HHS; R01 DK52115/DK/NIDDK NIH HHS; R01 DK58993/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Bacterial; 0/Antibodies, Monoclonal; 0/Shiga Toxin 2
Comments/Corrections

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