Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01889 (ankylosing spondylitis)
5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Some microorganisms which are pathogenic in humans share amino acid sequences with human proteins (molecular mimicry). It has been suggested that molecular mimicry might be a reason for autoimmunity as a result of immunological cross reactivity. A homologous sequence of six amino acids has been found in both Klebsiella pneumoniae nitrogenase and the HLA-B27.5 molecule. In addition, (auto)antibodies to a synthetic peptide that contained the HLA-B27.5/klebsiella mimicking epitope have been detected in serum samples from HLA-B27 positive patients with ankylosing spondylitis and Reiter's syndrome. Confirmation of these data is important, because ankylosing spondylitis and Reiter's syndrome have so far been assumed to be 'seronegative' rheumatic diseases. It was, however, not possible to confirm the presence of autoantibodies against the mimicking peptide in serum samples from patients with ankylosing spondylitis and Reiter's syndrome. Serum samples from 81 patients with ankylosing spondylitis, 38 patients with Reiter's syndrome, and 81 healthy blood donors were tested against the 'mimicking peptide' in an enzyme linked immunosorbent assay (ELISA). Some of the serum samples from patients showed high but non-specific binding to the mimicking peptide. A highly significant correlation between binding to plastic coated with the mimicking peptide, to plastic coated with an irrelevant peptide, and even to non-coated plastic was observed. The nature of the serum component(s) in these patient serum samples (and some control serum samples) responsible for the high non-specific binding to plastic remains unclear. It was also shown that antibodies to the HLA-B27 peptide (containing the mimicking epitope) induced in rabbits do not cross react with the klebsiella peptide and vice versa.
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PMID:Absence of autoantibodies to peptides shared by HLA-B27.5 and Klebsiella pneumoniae nitrogenase in serum samples from HLA-B27 positive patients with ankylosing spondylitis and Reiter's syndrome. 161 64

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

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

Fifty-six patients with ankylosing spondylitis and 87 healthy controls were screened for Klebsiella strains in their stools using a new highly sensitive culture medium. The presence of Klebsiella strains in the patient group was compared with activity of the disease. In a dynamic study changes in Klebsiella quantity over a period of 3 months were compared with changes in disease activity over the same period. The patient and control group showed similar percentages of Klebsiella carriage. In the patient group no temporal relation could be found between activity of the disease and the presence of Klebsiella in the intestinal tract.
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PMID:No conclusive evidence of an epidemiological relation between Klebsiella and ankylosing spondylitis. 185 8

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

Antibodies to Salmonellae, Yersiniae, Campylobacter jejuni, Borrelia burgdorferi, Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis and Chlamydia trachomatis were measured by ELISA in the sera of 99 patients with ankylosing spondylitis. Increased prevalence of IgA and IgG class antibodies against K. pneumoniae and of IgA class against E. coli was observed in ankylosing spondylitis. No clear correlation between the disease activity and occurrence of antibodies was revealed. The results are in line with the previously published findings suggesting that K. pneumoniae may have a role in the aetiopathogenesis of ankylosing spondylitis.
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PMID:Bacterial antibodies in ankylosing spondylitis. 204 28

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

We previously reported elevated serum antibody levels to a peptide representing the HLA-B27 polymorphic region (B27 peptide) in HLA-B27(+) ankylosing spondylitis (AS) patients. A plasmid (pHS-2) isolated from arthritogenic Shigella flexneri strains had been shown to encode an amino acid sequence homologous to HLA-B27. Rabbit antibody to this sequence (pHS-2 peptide) strongly cross-reacted with B27 peptide and, to a much lesser extent, with Klebsiella nitrogenase peptide. Serum antibody levels to pHS-2 peptide were studied in 160 spondylarthropathy patients. 12 of 115 (10.4%) AS patients, 2 of 45 (4.4%) patients with Reiter's syndrome or reactive arthritis as well as 6 of 147 (4.1%) normal controls were shown to have elevated anti-pHS-2 peptide antibodies. Antibody levels to B27 and pHS-2 peptides were significantly correlated in 134 HLA-B27(+) patients (r = 0.333, P less than 0.001). 13 of 15 affinity-purified anti-B27 peptide antibodies from patients strongly cross-reacted with pHS-2 peptide, whereas only 3 weakly cross-reacted to nitrogenase peptide. Leucine appeared to be a critical residue for this cross-reaction. AS patients' anti-B27 peptide antibodies reacted with HLA-B27 transfected L cells. These results may suggest that pHS-2 peptide more efficiently "mimics" B27 peptide than does nitrogenase peptide. Involvement of pHS-2 in pathogenesis of spondylarthropathy through molecular mimicry mechanisms requires further study.
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PMID:Autoantibodies to the HLA-B27 sequence cross-react with the hypothetical peptide from the arthritis-associated Shigella plasmid. 221 8

Geczy found that rabbit sera raised against Klebsiella strain K43 cross-reacted with the cells from HLA-B27 positive patients with ankylosing spondylitis (AS). Other laboratories failed to reproduce these results. After a series of unsuccessful attempts, however, we managed to prepare one selective antiserum, using E. coli, isolated from a Dutch Bechterew patient, in offspring of rabbits Geczy sent us. Ever since we obtained irreproducible results only. This paper reports about the many attempts we have made to produce a discriminating antiserum for use in a combined vital stain and dye-exclusion assay.
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PMID:Trial and error in producing ankylosing-spondylitis-selective antisera according to Andrew Geczy. 225 90


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