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)

Various aspects of pathogenesis, or more broadly, aetiopathogenesis, in the field of B27 related disorders are considered. The main conclusions can be expressed as follows: Genetic factors are involved in the causation of the spondarthritides, although there is still controversy within individual disorders concerning the precise mode of inheritance. For instance, in some conditions evidence appears stronger for a Mendelian mechanism, in others for a multifactorial process. The mode of the HLA-B27-receptor interaction is not yet fully established, but there is strong support for the one gene cross-tolerance theory, in ankylosing spondylitis at least. It is likely that environmental factors 'collaborate' with genetic factors in causing spondarthritic disease. The factors in the environment have yet to be proved, but there is some evidence that micro-organisms such as Klebsiella and Yersinia are involved (e.g. ankylosing spondylitis, Reiter's disease, reactive arthritis). Of noninfective environmental factors, trauma could play a part, as suggested by the mode of onset and pattern of development of some examples of ankylosing spondylitis and psoriatic arthritis.
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PMID:Pathogenetic mechanisms in B27 associated diseases. 641 60

Total serum immunoglobulins and class specific serum antibodies to Klebsiella pneumoniae, Salmonella typhimurium, Yersinia enterocolitica and Pseudomonas aeruginosa were measured in 107 patients with ankylosing spondylitis (AS) and 110 healthy tissue typed controls by enzyme linked immunosorbent assay (ELISA). The specificity of this technique was confirmed by the use of specific bacterial murine antisera and by cross-absorption of human sera by specific bacteria. Total serum IgA in AS patients correlated with both erythrocyte sedimentation rate (ESR) (P less than 0.001) and C-reactive protein (P less than 0.05) and was significantly elevated compared to healthy individuals (P less than 0.001). A significant elevation of IgA antibodies to K. pneumoniae was detected in the serum of AS patients with active disease when compared to healthy controls (P less than 0.01). These studies support the involvement of an enterobacterial micro-organism in the pathogenesis of AS and further relate to the role of HLA-B27 in this disease.
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PMID:HLA-B27 and the immune response to enterobacterial antigens in ankylosing spondylitis. 660 43

Yersinia enterocolitica is suspected of involvement in the aetiology of reactive arthritis and ankylosing spondylitis. Its two major outer membrane proteins are important targets for IgA and other protein A reactive immunoglobulins in the sera of some patients with these diseases.
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PMID:Antibodies against cell envelope antigens of Yersinia enterocolitica in reactive arthritis and ankylosing spondylitis. 665 95

Sera from rabbits immunized with HLA-B27 lymphocytes showed increased activity against klebsiellal enterobacter antigens using immunodiffusion, bacterial agglutination (P less than 0.025), haemagglutination (P less than 0.001) and radiobinding assays (P less than 0.001). Immunoprecipitin lines were also produced by these antilymphocyte sera against extracts from Yersinia enterocolitica and Shigella sonnci microorganisms. Rabbit anti-klebsiella sera had lymphocytotoxic activity against HLA-B27 lymphocytes obtained from patients with ankylosing spondylitis (P less than 0.001). These results suggest partial cross-reactivity between some antigens found in several Gram-negative microorganisms and HLA-B27 lymphocytes.
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PMID:Ankylosing spondylitis, HLA-B27 and Klebsiella. I. Cross-reactivity studies with rabbit antisera. 676 56

Yersinia enterocolitica biotype I were isolated from faeces of 16% of 56 consecutive patients with diarrhoea or gastrointestinal symptoms and 2.8% of 109 healthy controls (p less than 0.01). Similar Yersinia biotypes were isolated from 4% of samples from 86 rheumatoid arthritis patients and 4.5% of samples from 140 ankylosing spondylitis patients examined regularly over an 8-month period. These results suggest that Yersinia enterocolitica biotype I are regular but infrequent inhabitants of the human gastrointestinal tract in south-east England. The increased isolation rate of these microorganisms from patients with enteric disease and from patients with exacerbations of HLA B27-related arthritic and ocular inflammatory disease justifies further investigations.
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PMID:Yersinia enterocolitica biotype I. Diarrhoea and episodes of HLA B27 related ocular and rheumatic inflammatory disease in South-East England. 698 42

Although the strong association of HLA-B27 with ankylosing spondylitis (AS) is well documented, the significance of this association is largely unknown. It has recently been reported that Klebsiella pneumoniae was present in the faeces of patients with AS more frequently than in healthy individuals, and that there appeared to be some cross-reactivity between HLA-B27 and Klebsiella. We have therefore attempted to gain an insight into the possible role of Klebsiella in the pathogenesis of AS. The results presented here indicate that HLA-B27 positive individuals with AS have a significantly lower in vitro lymphocyte responsiveness to Klebsiella antigens, as compared with B27 positive and B27 negative healthy controls. By contrast, B27 positive patients with AS as well as B27 positive and negative controls respond equally well to phytohaemagglutinin, Staphylococcus, Streptococcus, Yersinia and Shigella. To investigate a possible cross-reactivity between Klebsiella and HLA-B27, antisera were raised in rabbits against various isolates of Klebsiella. An antiserum to one isolate (427) of Klebsiella lysed the lymphocytes of B27 positive AS patients but not of B27 positive or B27 negative controls. These observations strongly suggest that some Klebsiella antigens cross-react with a gene product closely associated with HLA-B27 or possibly with a modified B27 antigen in patients with AS.
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PMID:The role of Klebsiella in the pathogenesis of ankylosing spondylitis. II Evidence for a specific B27-associated marker on the lymphocytes of patients with ankylosing spondylitis. 738 24

Ankylosing spondylitis and reactive arthritis are seronegative spondyloarthropathies, which are strongly associated with HLA-B27. Despite intensive investigation, the basis for this association is not clear. However, in recent years one favored hypothesis to explain this linkage has been that of molecular mimicry, i.e., sharing of linear or conformational epitopes common to microbial antigens and host structures. During the past few years several examples of molecular mimicry between HLA-B27 and microbial antigens have been described. Heat shock proteins, among others, have been considered as target candidates for autoimmune phenomena, because of the high degree of homology between bacterial and mammalian species. Reactive arthritis triggered by Yersinia or Salmonella provides a unique model for studying the pathogenetic mechanisms underlying human inflammatory joint diseases in general, because the arthritogenic microbes are known and well-characterized. We have described two bacterial proteins that share amino acid homology with HLA-B27, namely YadA (Yersinia adhesin) and OmpH, outer surface proteins of Yersinia and Salmonella, respectively. Notably, the area of identity of these amino acid sequences is located in the same place on the HLA-B27 molecule as a hexapeptide identical between Klebsiella nitrogenase and HLA-B27, and a pentapeptide shared by a Shigella flexneri protein and HLA-B27. We have investigated immune responses to a panel of synthetic peptides based on the HLA-B27-homologous portions of pathogen-specific antigens in patients with reactive arthritis and ankylosing spondylitis. One third of the patients have antibodies to the synthetic peptides. However, instead of recognizing the HLA-B27-homologous portion, the antibodies are directed against the flanking sequences of the synthetic peptides. The concept of the role of molecular mimicry between HLA-B27 and microbial antigens in the pathogenesis of spondyloarthropathies is discussed, with a conclusion that no convincing evidence for its significance exists at the present.
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PMID:Molecular mimicry: any role in the pathogenesis of spondyloarthropathies? 750 16

A Yersinia pseudotuberculosis serotype III outbreak in 1982 was characterized by a high frequency of post-infectious complications. Ten years later 16 out of the 19 patients originally included in the outbreak were reached for a follow up evaluation. Altogether nine patients suffered from chronic joint symptoms. Four of them were HLA B27-positive. Two of these had ankylosing spondylitis; one with severe erosive polyarthritis and secondary amyloidosis which led to uremia requiring haemodialysis and eventually to death, the other with ankylosis of the lumbar spine and sacroiliitis. None of the patients any longer had detectable anti-Yersinia antibodies. The long-term prognosis of Yersinia-triggered reactive arthritis is discussed.
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PMID:Ten-year follow up study of patients from a Yersinia pseudotuberculosis III outbreak. 755 60

Acute anterior uveitis (AAU) or iritis is an inflammatory disorder of the anterior structures of the eye that may be associated with a number of disease entities. A significant proportion of patients will have no evidence of an underlying disorder and are labeled as idiopathic. Within this group approximately 50% will possess the human leukocyte antigen, HLA-B27, and some will have an associated spondyloarthropathy such as ankylosing spondylitis or Reiter's syndrome. Nevertheless, a number of HLA-B27-positive patients have no apparent underlying rheumatic disorder. The potential interplay of HLA-B27 and certain infective agents in the pathogenesis of AAU is discussed with particular reference to Yersinia species. Presentation of a uveitogenic peptide, similar to the arthritogenic peptide model in spondyloarthropathies, may be a mechanism involved in the development of AAU. Experimental models in animals have increased our understanding of the roles of retinal proteins and bacterial peptides, as well as T cells and cytokines, in the pathogenesis of uveitis. As in animal models of arthritis, certain retinal peptides (in conjunction with adjuvant therapy) can induce uveitis in animals. The treatment of isolated AAU usually involves topical medication and the prognosis is good. Occasional cases, especially those associated with systemic disorders, may require the addition of systemic corticosteroids or other immunosuppressive medications.
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PMID:Acute anterior uveitis: clinical and experimental aspects. 766 47

The aim of the present study was to elucidate the connection between yersiniosis and chronic inflammation. During the period 1974-83, Yersinia enterocolitica infection was diagnosed in 458 hospitalized patients by antibody response, or isolation. The patients were followed for 4-14 years (1987); 160 were readmitted with chronic disease. Fifty-three patients had persistent joint complaints, 18 developed ankylosing spondylitis, 14 rheumatoid arthritis, and 17 iridocyclitis. Thirty-eight patients suffered from chronic abdominal pain, and another 28 from chronic diarrhoea. Two who underwent proctocolectomy microscopically had ulcerative colitis. Eleven patients developed neurological disease; others developed conditions such as chronic nephritis, thyroid disease, insulin-dependent diabetes, etc. Chronic hepatitis, found in 22 patients, was significantly correlated with positive test for antinuclear antibody and rheumatoid factor, and with death. Several patients developed chronic multiorgan disease, probably with chronic hepatitis as pivot. Regarding the whole material, the difference between observed and expected cumulative survival rates remained significant for 8 years (0.9189 < 0.9456; p < 0.025), indicating a substantial impact on long-term survival exerted by chronic yersiniosis.
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PMID:Yersinia enterocolitica: an inducer of chronic inflammation. 796 May 1


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