Immunoglobulin G directed against toxins A and B of Clostridium difficile in the general population and patients with antibiotic-associated diarrhea

Bacon, Alfred E.; Fekety, F. Robert

doi:10.1016/0732-8893(94)90021-3

Cited by 60 publications

(27 citation statements)

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“…Toxinreactive IgG and IgA can be detected in the intestine and serum and have the potential to block toxin binding to epithelial receptors and promote toxin clearance from the intestine (71). The presence of antibodies that are reactive to C. difficile TcdA has been positively correlated with asymptomatic carriage of C. difficile (32), although there are conflicting reports regarding whether naturally occurring antitoxin antibodies and intravenous immunoglobulin therapy (IVIG) affect the disease course (32,69,70,(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83). Questions thus remain as to the extent to which antibody levels may confer protection against CDI.…”

Section: Risk Factors For Developing CDImentioning

confidence: 99%

“…Natural anti-C. difficile TcdA and TcdB antibodies in the general population have been proposed to be protective factors against disease development (69,70). Toxinreactive IgG and IgA can be detected in the intestine and serum and have the potential to block toxin binding to epithelial receptors and promote toxin clearance from the intestine (71).…”

Section: Risk Factors For Developing CDImentioning

confidence: 99%

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Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

et al. 2017

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SUMMARY Beneficial microorganisms hold promise for the treatment of numerous gastrointestinal diseases. The transfer of whole microbiota via fecal transplantation has already been shown to ameliorate the severity of diseases such as Clostridium difficile infection, inflammatory bowel disease, and others. However, the exact mechanisms of fecal microbiota transplant efficacy and the particular strains conferring this benefit are still unclear. Rationally designed combinations of microbial preparations may enable more efficient and effective treatment approaches tailored to particular diseases. Here we use an infectious disease, C. difficile infection, and an inflammatory disorder, the inflammatory bowel disease ulcerative colitis, as examples to facilitate the discussion of how microbial therapy might be rationally designed for specific gastrointestinal diseases. Fecal microbiota transplantation has already shown some efficacy in the treatment of both these disorders; detailed comparisons of studies evaluating commensal and probiotic organisms in the context of these disparate gastrointestinal diseases may shed light on potential protective mechanisms and elucidate how future microbial therapies can be tailored to particular diseases.

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Section: Risk Factors For Developing CDImentioning

confidence: 99%

Section: Risk Factors For Developing CDImentioning

confidence: 99%

Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

et al. 2017

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“…It has been shown that many such donors express high anti-toxin A and anti-toxin B antibody serum titers. 38,39 In addition, high levels of anti-toxin A and anti-toxin B antibodies were present in the IVIG preparations and the recipients after infusion. [15][16][17]22 Although constituting only a small fraction of the total IVIG administered, these antitoxin antibodies are believed to neutralize toxin A and B and help the host recover from the disease.…”

Section: Discussionmentioning

confidence: 97%

Intravenous immunoglobulin for the treatment of severe Clostridium difficile colitis: An observational study and review of the literature

Abougergi

Broor

Cui

et al. 2010

Journal of Hospital Medicine

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“…Johnson et al measured anti-TcdA IgA and IgG in CDI patients and controls and found higher titers in convalescent CDI cases than healthy controls, but no correlation with clinical outcome, even when the ability of the antibodies to neutralize cytotoxicity was measured [24]. Similarly, Bacon and Fekety found antiTcdA/B IgG in 24% of healthy control blood samples, although titer by ELISA did not correlate with neutralizing activity, which was measured at up to 1:50 serum dilution [25]. This stands in contrast to an earlier study that found anti-TcdA or TcdB in over 64% of healthy blood donors, with high titres correlating with neutralization [26].…”

Section: Anti-c Difficile Antibodies In Primary Versus Recurring CDImentioning

confidence: 99%

Adaptive immune response to Clostridium difficile infection: A perspective for prevention and therapy

Rees

Steiner

2018

Eur J Immunol

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Clostridium difficile infection (CDI) is one of the most important nosocomial illnesses and a major cause of morbidity and mortality. While initial treatment of CDI is usually successful, unprovoked relapses remain an important and frustrating problem. This review examines the literature describing the natural immune response to CDI, and to what extent it can explain the propensity for relapses. In particular, we discuss studies on antibody and, to a lesser extent, B cell and T cell responses in CDI. Despite years of study, there remains incomplete understanding of the natural antibody response to the major pathogenic toxins, TcdA and TcdB, and other bacterial antigens, in CDI. Recent literature suggests that a specific subset of neutralizing antibodies that target the putative carbohydrate-binding domains of TcdB and possibly TcdA have the greatest protective ability. This is further supported by recent successful clinical trials of a humanized monoclonal antibody to the major toxin TcdB. A better understanding of how and why the most protective adaptive immune response develops may lead to improved vaccine and therapeutic targets for recurrent CDI. Keywords:Clostridium difficile r Immunotherapy r TcdA r TcdB r Vaccination IntroductionClostridium difficile is a gram positive, spore-forming anaerobic bacillus that colonizes the large intestine. While asymptomatic colonization is common, Clostridium difficile infection (CDI) typically develops after opportunistic growth that occurs when antibiotic treatment diminishes the host commensal microbiota [1,2]. CDI incidence and mortality have increased dramatically in the United States, Canada, and Europe in the last 20 years [3][4][5]. More than 450 000 cases of CDI occur every year in the United States, resulting in around 29 000 deaths and costs of up to $4.8 billion dollars [5].CDI is characterized by predominantly neutrophilic inflammation within the colonic mucosa and lumen [1,6]. In patients, this causes symptoms ranging from mild diarrhea to more severe or life threatening complications, such as pseudomembranous coliCorrespondence: Dr. Theodore S. Steiner e-mail: tsteiner@mail.ubc.ca tis, toxic megacolon and death [7]. These symptoms stem from two major C. difficile toxins, TcdA and TcdB, encoded by the genes tcdA and tcdB residing in the pathogenicity locus [8][9][10]. These two large glucosyltransferases, weighing 308 and 270 kDa respectively, are believed to bind most commonly via the C-terminal, carbohydrate-binding combined repetitive oligopeptide (CROP) domain to target gut epithelial cells. Once bound, the toxins enter the cell through receptor-mediated endocytosis and autodigest using a protease domain, liberating a glucosyltransferase domain that inactivates Rho GTPases within target cells, ultimately leading to rounding and apoptosis of the target cells [11,12].The most common treatment for CDI is antibiotic therapy. Typically, vancomycin, fidaxomicin, or metronidazole is effective for most patients. However, recurring CDI is an issue for approximatel...

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Immunoglobulin G directed against toxins A and B of Clostridium difficile in the general population and patients with antibiotic-associated diarrhea

Cited by 60 publications

References 8 publications

Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies

Intravenous immunoglobulin for the treatment of severe Clostridium difficile colitis: An observational study and review of the literature

Adaptive immune response to Clostridium difficile infection: A perspective for prevention and therapy

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