Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0519030 (Klebsiella)
 21,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As part of a larger study undertaken to determine whether the presence of faecal Klebsiella aerogenes was significantly associated with the clinical activity of ankylosing spondylitis, thirteen patients with ankylosing spondylitis and acute non-granulomatous anterior uveitis (ANGAU) were examined. The faeces of eleven of these thirteen patients were found to contain Klebsiella aerogenes. This association shows a statistical significance of P less than 0.01, and suggests that Klebsiella aerogenes may have an aetiological role in the development of anterior uveitis in HLA B27 positive patients. The possible mechanism of this association and its potential clinical significance are discussed.
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PMID:Role of environmental factors in uveitis. 39 4

A search for the presence of Klebsiella-Enterobacter spp. and Yersinia enterocolitica in urine and faeces of 63 patients with ankylosing spondylitis was conducted because these microorganisms have been demonstrated to cross-react immunologically with HL-A B27 positive lymphocytes. The patients were graded into three groups on the basis of disease activity. Klebsiella spp. were found in the faeces of 13 (93%) of the 14 patients with 'active' disease, 10 (48%) of the 21 patients with 'probably active' disease and in one (4%) of the 28 patients with 'inactive' disease. Positive cultures were also obtained in 47 (38%) of 124 controls. It is suggested that the presence of Klebsiella spp. in faecal cultures may be associated with 'active' disease in patients with ankylosing spondylitis.
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PMID:Ankylosing spondylitis: klebsiella and HL-A B27. 91 95

The three-dimensional structure of the HLA class I molecules has highlighted the importance of the "groove" formed by the helices. We used site-directed mutagenesis to construct a series of HLA-B27 mutants with different substitutions at the sites of the conserved amino acid residues of HLA-B27 subtypes, specifically residue 77 which is thought to be critical to the binding site of the molecule, and a residue at the CD8 binding site. We formed an anti-B27 CTL line and derived six anti-B27 clones. Each of the six clones showed a different pattern of reaction, reflecting the diversity of the epitopes recognized. All nine mutants were effective in altering allorecognition by HLA-B27 specific CTL, although positions 45 and 77 caused the most drastic effect. The residue in position 77 is also the last amino acid of the peptide sequence shared with Klebsiella. Our results highlight the importance of certain epitopes in allorecognition that may have important implications for the immunotherapy of autoimmune diseases.
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PMID:Effect of the substitution of critical residues on the allorecognition of HLA-B27. 128 53

Many human diseases are associated with HLA class I, class II and class III antigens. It appears that the class III antigen disease associations can be explained by a direct defect operating at the level of either the class III gene or its gene product. The mechanism underlying class I and class II antigen disease associations is at present unknown. In this review we have considered thirty diseases which have been ranked according to their relative risk as defined by the frequency of a given HLA antigen in patient and control populations. The chronic inflammatory disorder, ankylosing spondylitis and its association with HLA B27 has been used as a model to study the HLA linked diseases. We have suggested that the disease may be caused by the Gram-negative microorganism Klebsiella which has antigenic similarity to HLA B27. It is proposed that some antibodies made against Klebsiella bind to HLA B27, thereby acting as autoantibodies leading to the pathological sequelae of chronic inflammatory arthritis. This is the crosstolerance hypothesis or molecular mimicry model and it has been compared to the receptor model. It is further suggested that the crosstolerance hypothesis can be utilised as a general theory to explain the association of other diseases with the class I and class II antigens, and offer a possible explanation for the polymorphism of HLA.
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PMID:HLA and disease. 128 96

The suggested relationship of Klebsiella species to the pathogenesis of ankylosing spondylitis reflects evidence that there was an increase in fecal Klebsiella carriage in patients with active AS when compared to controls, that B27-positive lymphocytes from AS patients could be distinguished from normal B27-positive lymphocytes by an antiserum, and that a nitrogenase enzyme found in some species of Klebsiella had a sequence of six amino acids identical to a sequence seen in B*2705. It is the authors' view that the superficial similarities between these observations has been the chief factor leading to their support but that on close observation none are attractive either on pragmatic or on intuitive grounds.
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PMID:Ankylosing spondylitis is not caused by Klebsiella. 156 12

The binding of rabbit anti-Klebsiella antibodies to tissue-typed lymphocytes obtained from 30 ankylosing spondylitis (AS) patients and 54 healthy subjects has been measured by an enzyme immunoassay method. HLA B27 positive lymphocytes obtained from either AS patients (t = 3.60; p less than 0.001) or healthy subjects (t = 3.77; p less than 0.001) were found to bind Klebsiella antibodies to a significantly greater extent than non-B27 lymphocytes obtained from healthy controls. Absorption studies demonstrated that HLA B27 positive lymphocytes absorbed out significantly more anti-Klebsiella antibodies than HLA B27-negative lymphocytes (t = 6.76; p less than 0.005). These results are compatible with cross-reactivity or molecular mimicry between HLA B27 and epitopes on some Gram-negative bacteria such as Klebsiella.
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PMID:The use of enzyme immunoassay (EIA) and radiobinding assay to investigate the cross-reactivity of Klebsiella antigens and HLA B27 in ankylosing spondylitis patients and healthy controls. 169 67

Two new examples of amino acid homology between HLA B27 and microbes triggering HLA B27-associated diseases are described. An outer membrane protein YadA (Yersinia adhesin, previously called Yop1) of Yersinia enterocolitica and Y. pseudotuberculosis shares a linear tetrapeptide with HLA B27. A cationic outer membrane protein OmpH of Salmonella typhimurium shares homology with five amino acids of HLA B27 in a non-linear fashion. The four amino acids of YadA are also notably included in the hexapeptide identical between Klebsiella pneumoniae nitrogenase and HLA B27, and three of them occur in the pentapeptide shared by a Shigella flexneri protein and HLA B27. Antibodies against synthetic peptides including HLA B27 homologues sequences of YadA and OmpH were observed in one-third of the patients with HLA B27 associated diseases. Antibodies were directed against a flanking sequence next to the amino acid sequences shared by arthritis-triggering microbes and HLA B27. The area of identity in each example of this molecular mimicry (Yersinia, Salmonella, Shigella and Klebsiella) is located in the same place on the HLA B27 molecule: between amino acids 70 to 78 in the variable region of alpha 1-helix. This area of HLA B27 molecule includes sites predicted to be important for binding processed antigens.
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PMID:Molecular mimickry between HLA B27 and Yersinia, Salmonella, Shigella and Klebsiella within the same region of HLA alpha 1-helix. 174 48

One hundred and fourteen patients with acute anterior uveitis were studied for the presence of the HLA-B27 tissue type, the prevalence of spondylitis and arthritis and the occurrence of gastro-intestinal and urogenital infections or diarrhoeal illness in the history. Eighty-seven (76%) were B27+ and 27 (24%) B27-. Forty-two (48%) of the B27+ group had ankylosing spondylitis (AS); 13 (30%) of them were females. Sacroilitis (SI) with no spinal involvement was present in 21 patients (24%), 13 (61%) males and 8 (38%) females. Peripheral arthritis occurred in 6 patients. Thus, 68 (78%) of the HLA-B27+ positive patients had inflammatory spinal and/or joint disease, compared with 1 (4%) of the HLA-B27- group (p less than 0.001). The AS diagnosis was unknown previous to our examination in 31% of the males and 54% of the females, and SI was undiscovered in 61% of the males and 62% of the females. The occurrence of acute enteric infections was significantly increased in the B27+ AAU group, compared with the B27- patients and the patients reported exacerbation of AAU in connection with episodes of diarrhoea. An increased occurrence of urogenital infections was shown only in co-comparison with the males of the B-27+ AAU group. Thirty-three out of 47 AAU patients assayed by enzyme immuno-assay (EIA) for the quantification of IgM, IgA and IgG antibodies against Klebsiella pneumoniae, E coli, and Proteus mirabilis had significantly raised antibody titres against one or more of the antibodies studied, as compared to 62 healthy controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute anterior uveitis, arthritides and enteric antigens. 180 94

Ankylosing spondylitis is one of the oldest diseases in humans; however, it is still one of the most fascinating and mysterious in human pathology. The unusual combination of both fundamental pathological processes: inflammation and ossification (which are mostly independent in respect to time and place) is unique. Until 1973, ankylosing spondylitis did not attract much immunological research. After the detection of an association between HLA B27 and the disease, clinical and immunological research was stimulated. It was supposed that HLA B27 may be a pathogenic factor. Meanwhile, it has become well known that HLA B27 itself is not required for development of the disease; however, discovery of immunological cross-reactivity between HLA B27 and some Klebsiella antigens inspired pathogenic considerations. It is discussed that the structural similarities between enteric bacteria and HLA B27 induce autoantibodies, or that HLA B27 plays a role in antigen recognition. Possibly, HLA B27 may also act as a receptor for infectious agents and their products. Fascinating, but controversely discussed is the hypothesis that bacterial products modify the B27 molecule and, in this way, trigger the disease. All present theories about pathogenesis of ankylosing spondylitis are unsatisfactory, because many important questions cannot be answered. There are no explanations for the unusual affinity of possible pathogenic immune reactions to the spine and other organs, the induction of ossification, the merging of cartilage, or the development of sacroilitis. Especially, we do not know the important bridge (if one exists) between inflammation and ossification. The typical ossification of the spine is of dramatic consequence for the patient in respect to function and mobility.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[New pathogenetic aspects of ankylosing spondylitis]. 187 44

74 overlapping peptides of varying lengths from Klebsiella pneumoniae nitrogenase reductase (residues 181-199) and from the HLA B27.1 molecule (residues 65-85) were synthesized and tested by ELISA against sera from HLA B27+ ankylosing spondylitis (AS) patients, and sera from HLA B27+ and HLA B27- healthy first-degree relatives. Antibody activity in AS sera to Klebsiella peptides of four to eight amino acids was maximal with the peptide NSRQTDR. Activity to HLA B27 peptides was maximal with the peptide KAKAQTDR (named epitope I). These peptides overlap with, but are proximal to the NH2 terminus from QTDRED, which is homologous in HLA B27.1 and K. pneumoniae nitrogenase reductase. A second weaker reactive site was noted in the HLA B27.1 peptides, proximal to the COOH terminus from the homologous sequence, namely peptide REDLRTLL (named epitope II). Little activity was seen against peptides that included the entire homologous sequence. Sera from 50 AS patients showed higher total Ig activity against peptides KAKAQTDR (p less than 0.001) and NSRQTDR (p less than 0.02) than did sera from 22 B27+ and 22 B27- healthy controls. These data indicate that AS patient sera contain antibodies that bind to K. pneumoniae nitrogenase peptides and HLA B27.1 peptides, and that there are at least two epitopes on HLA B27.1 in the alpha 1 domain, at the MHC groove region, that are autoantigenic in AS patients. Epitope I may be a site for crossreactivity between HLA B27 and Klebsiella.
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PMID:Antibody activity in ankylosing spondylitis sera to two sites on HLA B27.1 at the MHC groove region (within sequence 65-85), and to a Klebsiella pneumoniae nitrogenase reductase peptide (within sequence 181-199). 218 31


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