Association of interleukin-8 polymorphism and immunoglobulin G anti-toxin A in patients with Clostridium difficile-associated diarrhea.
OBJECTIVE
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.
Jiang
Zhi-Dong
ZD
Center for Infectious Diseases, 1200 Herman Pressler, Room 739, University of Texas-School of Public Health, Houston, Texas 77030, USA. zhidong.jiang@uth.tmc.edu
Garey
Kevin W
KW
Price
Margaret
M
Graham
Gail
G
Okhuysen
Pablo
P
Dao-Tran
Thanh
T
LaRocco
Mark
M
DuPont
Herbert L
HL
D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D016360:Clostridioides difficile / Q000302:isolation & purification; D004247:DNA / Q000235:genetics*; D003967:Diarrhea / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D004761:Enterocolitis, Pseudomembranous / Q000150:complications / Q000235:genetics / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D005964:Glucosyltransferases; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D012189:Retrospective Studies
D000888:Antibodies, Anti-Idiotypic; D001427:Bacterial Toxins; D004768:Enterotoxins; D007074:Immunoglobulin G; D016209:Interleukin-8; C041348:tcdA protein, Clostridium difficile; D004247:DNA; D005964:Glucosyltransferases