Abstract
Clostridium difficile infection has emerged as a growing worldwide health problem. The colitis of Clostridium difficile infection results from the synergistic action of C. difficile secreted toxins A and B upon the colon mucosa. A human monoclonal IgG anti-toxin has demonstrated the ability in combination therapy to reduce mortality in C. difficile challenged hamsters. This antibody is currently in a clinical trial for the treatment of human Clostridium difficile infection. More than one group of investigators has considered using polyclonal bovine colostral antibodies to toxins A and B as an oral passive immunization. A significant proportion of the healthy human population possesses polyclonal antibodies to the Clostridium difficile toxins. We have demonstrated that polyclonal IgA derived from the pooled plasma of healthy donors possesses specificity to toxins A and B and can neutralize these toxins in a cell-based assay. This suggests that secretory IgA prepared from such pooled plasma IgA may be able to be used as an oral treatment for Clostridium difficile infection.
Highlights
Clostridium difficile (C. difficile) infection (CDI) is a serious and growing worldwide health problem
We have demonstrated that polyclonal IgA derived from the pooled plasma of healthy donors possesses specificity to toxins A and B and can neutralize these toxins in a cell-based assay
This suggests that secretory IgA prepared from such pooled plasma IgA may be able to be used as an oral treatment for Clostridium difficile infection
Summary
Clostridium difficile (C. difficile) infection (CDI) is a serious and growing worldwide health problem. The advantages of oral immunotherapy with IgA are that the antibodies are delivered to the intestines where the CdtA and CdtB are active, and that treatment is more accomplished in outpatients. We believe that such an anti-C. difficile toxin antibody administration in combination with antibiotic treatment will decrease morbidity and death in patients at increased risk. Dimeric IgA is present in plasma [15,16,17] This is important because we propose that IgA derived from the plasma of healthy donors contains IgA with specificity to the C. difficile toxins A and B
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