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

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 and-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 mu g/mL seen in 10 anti-toxin A antibody-negative subjects with CDAD. Conclusions: This study provided evidence that host susceptibly to C. difficile diarrhea is related both to a defective humoral immune response to CD toxin A and host IL-8 AA genotype.