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)

Acute anterior uveitis (AAU) and ankylosing spondylitis (AS) are, like reactive arthritis (ReA), strongly associated with HLA-B27. Mucosal infections play a role in the pathogenesis of ReA. To investigate whether these microorganisms are also involved in the pathogenesis of AAU and AS, we examined blood samples from patients with AAU, AS or both, and healthy controls for presence of antibodies against Klebsiella pneumoniae (K 30), Salmonella enteritidis and S. typhimurium, Chlamydia trachomatis, Proteus mirabilis and Borrelia burgdorferi. The IgA, IgG and IgM classes of these antibodies were measured using an enzyme-linked immunosorbent assay. No significant differences were found in the frequency in which these antibodies occurred in HLA-B27 positive patients with AAU or AS and healthy controls. However, IgA antibodies against K. pneumoniae (p < 0.01) and IgA and IgG antibodies against P. mirabilis (p < 0.01 and p < 0.05) were detected more frequently in HLA-B27 negative patients with AAU than in healthy controls. The results of this study are in contrast with various earlier reports in which antibodies against Klebsiella strains were more frequently found in patients with HLA-B27 associated ankylosing spondylitis than in healthy controls.
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PMID:IgA antibodies in HLA-B27 associated acute anterior uveitis and ankylosing spondylitis. 883 4

The discovery that HLA-B27 is linked to ankylosing spondylitis (AS) and HLA-DR1/DR4 to rheumatoid arthritis (RA) has provided new approaches to the study of the possible causation of these diseases. Several theories have been proposed to explain these associations but only one, namely "molecular mimicry", has provided a specific aetiological agent for each of these diseases. Molecular mimicry between HLA-B27 and two molecules in Klebsiella microbes: nitrogenase and pullulanase D has been reported whilst in Proteus microbes, the haemolysin molecule shows sterochemical similarity to HLA-DR1/DR4. Elevated immune responses to Klebsiella microbes have been demonstrated in AS patients from 10 different countries and this wide geographical distribution suggests that the same aetiological agent is probably acting in producing this condition. Furthermore RA patients show similar immune responses to Proteus microbes. Whether AS or RA are caused by these bacteria can only be resolved by tissue typing all rheumatological patients early, in the course of their disease and then assessing their response to antibiotic chemotherapy in longitudinal studies involving double-blind crossover trials. It is possible that in the future, the course of AS or even RA could be modified by adequate antibiotic chemotherapy or even diets which affect the substrates on which these bacteria grow.
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PMID:Molecular mimicry: the geographical distribution of immune responses to Klebsiella in ankylosing spondylitis and its relevance to therapy. 883 5

Specific immunoreactive anti-Klebsiella antibodies are found in patients with ankylosing spondylitis (AS), a significant proportion of whom have occult inflammatory bowel disease. Molecular mimicry between Klebsiella or other bacterial antigens and HLA-B27 has been suggested in the pathogenesis of AS. The specificity of increased immunoreactivity against Klebsiella remains to be assessed against the abundant anaerobic bacterial flora, present either in healthy controls or in patients with ulcerative colitis (UC) and Crohn's disease (CD). Total immunoglobulin (Ig; IgG, IgA, IgM) immunoreactivity was measured by ELISA against Klebsiella pneumoniae, Proteus mirabilis, Escherichia coli and ten anaerobic isolates of the predominant normal bowel flora in 35 patients with active AS, 60 patients with inflammatory bowel disease (30 CD, 30 UC), 60 patients with active rheumatoid arthritis (RA) and 60 healthy controls. Ig immunoreactivity to K. pneumoniae was significantly elevated in AS (P < 0.001), CD (P < 0.001) and UC (P < 0.001) patients compared with RA patients and healthy controls. Furthermore, Ig immunoreactivity to P. mirabilis was significantly elevated only in RA patients, compared with the other inflammatory groups (P < 0.001) and controls (P < 0.001). There was no significant antibody response against E. coli or the ten obligate anaerobes in any of the test groups. The data suggested an increased immune response to Klebsiella in patients with AS, UC, CD and to Proteus in patients with RA. The specificity of these responses in some patients supported a possible role for enteric Klebsiella in the pathogenesis of AS and Proteus in RA. The role of Klebsiella in inflammatory bowel disease requires further study.
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PMID:Antibody responses to gut bacteria in ankylosing spondylitis, rheumatoid arthritis, Crohn's disease and ulcerative colitis. 919 9

IgM, IgG and IgA class antibodies against three Klebsiella pneumoniae capsular types, Escherichia coli and Proteus mirabilis, as well as total immunoglobulin concentrations, were measured by enzyme immunoassay and radial immunodiffusion technique, respectively, in paired serum and synovial fluid samples from eight patients with ankylosing spondylitis and 10 with rheumatoid arthritis. No clear evidence for intra-articular antibody production against any of the studied microbes was found.
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PMID:IgM, IgG and IgA class enterobacterial antibodies in serum and synovial fluid in patients with ankylosing spondylitis and rheumatoid arthritis. 937 20

It has been well established that many diseases are linked to HLA antigens. Two of the most interesting HLA associations may provide some insight into the pathogenesis of rheumatic inflammatory conditions. In ankylosing spondylitis (AS), 96% of patients possess HLA-B27, whilst the frequency of this marker in the general population is c. 8%. In rheumatoid arthritis (RA), >90% of patients possess either HLA-DR1 or some subtypes of HLA-DR4, whilst the frequency of this marker in the general population is c. 35%. The association between HLA-B27 and reactive arthritis (ReA) has also been well established. Furthermore, it has been shown that ReA is triggered by infection via the gastrointestinal tract due to Yersinia, Salmonella or Campylobacter spp. and in the genitourinary tract due to chlamydia. In a similar way, microbiological and immunological studies have revealed an association between Klebsiella pneumoniae in AS and Proteus mirabilis in RA. This article reviews the possible pathological implications of the associations between HLA-B27, K. pneumoniae and AS, as well as HLA-DR1/DR4, P. mirabilis and RA.
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PMID:HLA molecules, bacteria and autoimmunity. 1075 23

Autoimmune diseases have environmental and genetic components. These are the microbial trigger, the immunity system component and the genetic component. Here we describe these components and how they interact. Known microbial triggers are Streptococcus pyogenes for rheumatic carditis, Proteus mirabilis for rheumatoid arthritis and Klebsiella pneumoniae for ankylosing spondylitis. The immunity system component has been clarified by realisation that no autoimmune disease is caused by loss of suppressor T cells. This leaves Burnet's forbidden clones, clearly seen in Graves' disease, as the immunological defect. With wide scope for clonal diversification by somatic gene mutations, to prevent frequent autoimmunity the immunity system is policed by the histocompatibility system. This dictates the immune response repertoire by deleting complementary clones (H Gene Theory). We show molecular evidence of how specific histocompatibility antigens can predispose to an autoimmune disease by influencing choice of the microbial antigen to which the immunity system reacts. Because of the unlucky random element in the somatic mutations involved in their development, forbidden clones are unlikely to reappear in new immune repertoires developing after immune ablation and autologous bone marrow cell reconstitution, as observed clinically. Isolation of autoantigens and their attachment to cytotoxic moieties could provide specific immunotherapy for autoimmune diseases. Kaplans's discovery that xenografts can be accepted without rejection after immune ablation followed by autologous and xenogeneic bone marrow inoculation, could enable widespread use of pig grafts for humans.
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PMID:Autoimmune diseases: Solution of the environmental, immunological and genetic components with principles for immunotherapy and transplantation. 2008 35

A general consensus supports fundamental roles for both genetic and environmental, mainly microbial, factors in the development of autoimmune diseases. One form of autoimmune rheumatic diseases is confined to a group of nonpyogenic conditions which are usually preceded by or associated with either explicit or occult infections. A previous history of clinical pharyngitis, gastroenteritis/urethritis, or tick-borne skin manifestation can be obtained from patients with rheumatic fever, reactive arthritis, or Lyme disease, respectively, whilst, other rheumatic diseases like rheumatoid arthritis (RA), ankylosing spondylitis (AS), and Crohn's disease (CD) are usually lacking such an association with a noticeable microbial infection. A great amount of data supports the notion that RA is most likely caused by Proteus asymptomatic urinary tract infections, whilst AS and CD are caused by subclinical bowel infections with Klebsiella microbes. Molecular mimicry is the main pathogenetic mechanism that can explain these forms of microbe-disease associations, where the causative microbes can initiate the disease with consequent productions of antibacterial and crossreactive autoantibodies which have a great impact in the propagation and the development of these diseases.
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PMID:Autoimmunity in Rheumatic Diseases Is Induced by Microbial Infections via Crossreactivity or Molecular Mimicry. 2245 61


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