Colonic IgA producing cells and macrophages are reduced in recurrent and non-recurrentClostridiumdifficileassociated diarrhoea

Johal, S S; Lambert, Christian; Hammond, Jeremy; James, P D; Borriello, S. P.; Mahida, Yashwant R.

doi:10.1136/jcp.2003.015875

Cited by 55 publications

(34 citation statements)

References 40 publications

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“…28,29) The risk of recurrent disease has been shown to be related to the host immune response. 30,31) In this study, we demonstrated that the starting days of anticancer agents and steroids after CDI therapy were significantly longer in the patients without recurrence than in the patients with recurrence (Table 7). Thus, the recurrence of CDI may be caused by the reactivation of C. difficile with immunosuppressive effects.…”

Section: Discussionmentioning

confidence: 78%

Factors Affecting Treatment and Recurrence of Clostridium difficile Infections

Matsumoto

Kanazawa

Shigemi

et al. 2014

Biological & Pharmaceutical Bulletin

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The antimicrobial agents vancomycin and metronidazole have been used to treat Clostridium difficile infections (CDIs). However, it remains unclear why patients are at risk of treatment failure and recurrence. Therefore, this study retrospectively examined 98 patients with CDIs who were diagnosed based on the detection of toxin-positive C. difficile to determine the risk factors affecting drug treatment responses and the recurrence of CDI. No significant difference was observed in the cure rate or dosage between the vancomycin and metronidazole groups. The 90-d mortality rate and total number of drugs associated with CDIs, including antiinfective agents used within 2 months before the detection of toxin-positive C. difficile, were significantly lower in the treatment success group than in the failure group. The total number of antiinfective agents and gastric acid-suppressive agents used during CDI therapy was also significantly lower in the success group than in the failure group. The period from the completion of CDI therapy to restarting the administration of anticancer agents and steroids was significantly longer in patients without than in patients with recurrence. These results indicate that the total number of drugs associated with CDIs should be minimized to reduce the risk of CDIs, that not only antibiotics but also gastric acid-suppressive agents should be discontinued during CDI therapy to increase therapeutic efficacy, and that the use of anticancer agents and steroids should be delayed as long as possible after patients are cured by CDI therapy to prevent recurrence.

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Section: Discussionmentioning

confidence: 78%

Factors Affecting Treatment and Recurrence of Clostridium difficile Infections

Matsumoto

Kanazawa

Shigemi

et al. 2014

Biological & Pharmaceutical Bulletin

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“…On the other hand, studies using anti-immunoglobulin antibodies showed significant reductions in IgA-producing cells in CDI biopsy specimens (P Ͻ 0.05), with the greatest reduction in samples from patients with pseudomembranous colitis. Johal et al concluded that a selective reduction in mucosal IgAproducing cells and macrophages is associated with colonic disease in C. difficile-infected patients and that a severe reduction in colonic IgA-producing cells may predispose to a recurrence of CDI (16). Many studies have shown that the presence of C. difficile or CDI is associated with decreased levels of bifidobacteria.…”

Section: Discussionmentioning

confidence: 99%

Clostridium difficile Colonization in Early Infancy Is Accompanied by Changes in Intestinal Microbiota Composition

et al. 2011

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Clostridium difficile is a major enteric pathogen responsible for antibiotic-associated diarrhea. Host susceptibility to C. difficile infections results partly from inability of the intestinal microbiota to resist C. difficile colonization. During early infancy, asymptomatic colonization by C. difficile is common and the intestinal microbiota shows low complexity. Thus, we investigated the potential relationship between the microbiota composition and the implantation of C. difficile in infant gut. Fecal samples from 53 infants, ages 0 to 13 months, 27 negative and 26 positive for C. difficile, were studied. Dominant microbiota profiles were assessed by PCR-temporal temperature gradient gel electrophoresis (TTGE). Bacterial signatures of the intestinal microbiota associated with colonization by C. difficile were deciphered using principal component analysis (PCA). Resulting bands of interest in TTGE profiles were excised, sequenced, and analyzed by nucleotide BLAST (NCBI). While global biodiversity was not affected, interclass PCA on instrumental variables highlighted significant differences in dominant bacterial species between C. difficile-colonized and noncolonized infants (P ‫؍‬ 0.017). Four bands were specifically associated with the presence or absence of C. difficile: 16S rRNA gene sequences related to Ruminococcus gnavus and Klebsiella pneumoniae for colonized infants and to Bifidobacterium longum for noncolonized infants. We demonstrated that the presence of C. difficile in the intestinal microbiota of infants was associated with changes in this ecosystem's composition. These results suggest that the composition of the gut microbiota might be crucial in the colonization process, although the chronology of events remains to be determined.

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“…For example, while Kyne et al [32] demonstrated that serum anti-toxin A IgG antibodies correlated with protection against CDI, toxin-neutralizing activity was shown to be present exclusively in the IgA class of antibodies in vivo and in vitro [29][30][31]42] specifically IgA1 [43]. Similarly, Johal et al [44] demonstrated that colonic IgA-producing cells and macrophages were reduced in colonic biopsies of patients with CDI, and these levels were even lower in patients who subsequently relapsed compared to those who had only a single CDI episode. However, analysis of IVIG preparations demonstrated high anti-toxin A IgG antibody levels, but undetectable anti-toxin A IgA antibodies [25].…”

Section: Ivig Mechanism Of Action In C Difficile Infection Treatmentmentioning

confidence: 97%

Intravenous Immunoglobulin for the Treatment of Clostridium difficile Infection: A Review

Abougergi

Kwon

2010

Dig Dis Sci

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Clostridium difficile infection (CDI) has increased sharply in incidence, mortality rate, and burden on the healthcare system over the past decade. Therefore, novel treatment modalities have been developed, including intravenous immunoglobulin (IVIG). The level of immune response to Clostridium difficile colonization is the major determinant of the magnitude and duration of clinical manifestations. This effect is mediated predominantly by serum IgG anti-toxin A antibodies. Based on this finding, anti-toxin A and B antibodies were successfully used in multiple in vitro and in vivo experimental settings to passively immunize hamsters in CDI models. In humans, IVIG was used as the source of those antibodies. Fifteen small, mostly retrospective and non-randomized reports documented IVIG's success in the treatment of protracted, recurrent, or severe CDI. Diarrhea resolution rates were higher in the former patient group, but the recurrence rates were similar. IVIG mechanism of action is neutralization of mainly toxin A through IgG anti-toxin A antibodies. Purified anti-toxin A and B antibodies were successfully used to decrease CDI recurrence rates among patients with no or one previous CDI episodes. In conclusion, the efficacy of IVIG for CDI treatment in animal models has been convincingly demonstrated. However, only few small non-randomized, mostly uncontrolled reports have been published on human subjects. A phase II trial results support the use of purified anti-toxin A and B antibodies to decrease CDI recurrence rates. Therefore, IVIG should currently only be used as adjunct therapy until results from large, randomized controlled trials are available.

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Colonic IgA producing cells and macrophages are reduced in recurrent and non-recurrentClostridiumdifficileassociated diarrhoea

Cited by 55 publications

References 40 publications

Factors Affecting Treatment and Recurrence of <i>Clostridium difficile</i> Infections

Factors Affecting Treatment and Recurrence of <i>Clostridium difficile</i> Infections

Clostridium difficile Colonization in Early Infancy Is Accompanied by Changes in Intestinal Microbiota Composition

Intravenous Immunoglobulin for the Treatment of Clostridium difficile Infection: A Review

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