Characterization of the humoral immune response to Klebsiella species in inflammatory bowel disease and ankylosing spondylitis

Abstract

This study was carried out to characterize the antibody class response by ELISA to seven Klebsiella pneumoniae serotypes (K2, K3, K17, K21, K26, K36, K50) in five different groups, 40 HLA-B27-positive ankylosing spondylitis (AS) patients, 46 patients with Crohn's disease (CD), 38 patients with ulcerative colitis (UC), 50 patients with active anti-endomysial antibody-positive coeliac disease and 40 healthy controls, using whole bacteria and capsular polysaccharide. IgG antibody levels were significantly elevated in AS patients to K17, K36, K50; IgA to K2, K3, K21, K26, K36 and K50; and IgM to serotype K21 when compared to normal controls. Furthermore, IgG antibody levels were significantly elevated in CD patients to K2, K17, K21, K26, K36 and K50; IgA to K2, K3, K21, K26, K36 and K50; and IgM to K2, K3, K17, K21 and K50. Increased IgG antibody levels in the UC group were limited only to K17, K36 and K50. No antibody class was increased to any of the K. pneumoniae serotypes in the coeliac disease group. The immune responses in AS patients also involve Klebsiella bacteria having capsular serotypes other than K26, K36 and K50. The similarity in the immune responses between CD and AS groups suggests that many AS patients may have occult bowel inflammation.

Differences between Tissue-Associated Intestinal Microfloras of Patients with Crohn's Disease and Ulcerative Colitis

“…We also detected 43 Klebsiella pneumoniae 16S clones in only two CD patients and none of the other groups (P Ͻ 0.0001). Since antibody levels against K. pneumoniae were shown previously to be increased in CD patients (26,27), this finding may warrant a larger study using Klebsiella-specific primers or probes. Sulfate-reducing ␦-Proteobacteria were rare and encountered only in the CD group.…”

Inflammatory bowel disease and spondylarthropathy

“…Initial hypotheses that were put forth to account for an intestinal-spondylitic association in HLA-B27-positive patients with AS related to the demonstration of a shared amino acid stretch between B27 and a Klebsiella nitrogenase enzyme (68) or between certain subtypes of collagen and some other bacteria (69). The presence of Klebsiella pneumoniae in stool and increased serum antibody levels are evident in a proportion of patients with active disease (70,71). The "specificity" of these findings is suggested by the absence of an immunologic response to some other gram-negative bacteria (72).…”

Allele-dependent Similarity between Viral and Self-peptide Presentation by HLA-B27 Subtypes

“…Molecular mimicry (6 -9), i.e. similarity in overall shape as well as charge distribution for an interaction surface (9), has been invoked as an explanation for the association of HLA-B27 and spondyloarthropathies (10 -12), but its existence has yet to be proven (13,14). A principal difficulty is related to the fact that a host-derived epitope is expected to share antigenic but not necessarily also extensive sequence homology with a foreign antigen (15).…”