Association of interleukin-8 polymorphism and immunoglobulin G anti-toxin A in patients with Clostridium difficile-associated diarrhea

Clin Gastroenterol Hepatol. 2007 Aug;5(8):964-8. doi: 10.1016/j.cgh.2007.04.018. Epub 2007 Jul 6.

Abstract

Background & aims: Previous studies have shown that failure to produce serum antibodies to C. difficile (CD) toxin A is associated with more severe and recurrent C. difficile-associated diarrhea (CDAD); and that presence of AA genotype in the interleukin (IL)-8 gene promoter -251 position is associated with increased susceptibility to CDAD. This study examined the relationship between serum immunoglobulin G antibodies to CD toxin A and the presence of IL-8 AA genotype in hospitalized patients with CDAD.

Methods: At enrollment, blood for host IL-8 genotype, serum for CD anti-toxin A antibody, and stool for IL-8 by enzyme-linked immunosorbent assay were obtained in CDAD patients and in CD-toxin-negative asymptomatic controls.

Results: Nine of 24 (37.5%) CDAD and 3 of 20 (15%) controls were CD anti-toxin A positive (P = .095). Eleven of 24 (45.8%) CDAD subjects were positive for AA genotype compared with 5 of 20 (25.0%) controls (P = .0019). One of 11 (9.1%) CDAD with AA genotype were positive for anti-toxin A antibodies compared with 8 of 13 (61.5%) non-AA genotype CDAD (P < .0001). Fecal IL-8 concentration for the single antibody-positive CDAD subject with AA genotype was lower than the median level of 822 microg/mL seen in 10 anti-toxin A antibody-negative subjects with CDAD.

Conclusions: This study provided evidence that host susceptibility to C. difficile diarrhea is related both to a defective humoral immune response to CD toxin A and host IL-8 AA genotype.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antibodies, Anti-Idiotypic / immunology*
  • Bacterial Toxins / immunology*
  • Clostridium difficile / isolation & purification
  • DNA / genetics*
  • Diarrhea / etiology
  • Diarrhea / genetics*
  • Diarrhea / immunology
  • Enterocolitis, Pseudomembranous / complications
  • Enterocolitis, Pseudomembranous / genetics
  • Enterocolitis, Pseudomembranous / immunology
  • Enterotoxins / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Follow-Up Studies
  • Glucosyltransferases
  • Humans
  • Immunoglobulin G / immunology*
  • Interleukin-8 / genetics*
  • Interleukin-8 / metabolism
  • Middle Aged
  • Odds Ratio
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Prognosis
  • Retrospective Studies

Substances

  • Antibodies, Anti-Idiotypic
  • Bacterial Toxins
  • Enterotoxins
  • Immunoglobulin G
  • Interleukin-8
  • tcdA protein, Clostridium difficile
  • DNA
  • Glucosyltransferases