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 mechanism by which HLA-B27 confers genetic susceptibility to the seronegative spondyloarthropathies ankylosing spondylitis, Reiter's syndrome, and reactive arthritis, is not well understood. The current concept of an extraarticular bacterial infection functioning as the triggering event in a genetically susceptible host suggests the possibility of direct microbial-MHC interaction. We have addressed the role of HLA-B27 in microbial-host cell interaction by examining invasion by putatively arthritogenic gram-negative bacteria. Target cells used were murine L cells transfected with HLA-B27, HLA-A3, HLA-A2, HLA B44, HLA B18, or pSV2neo vector alone. Relative to the pSV2neo control and the HLA-A3 transfectant, HLA-B27-transfected cells demonstrated a consistent decrease in invasion for each of the following pathogens: Salmonella typhimurium (45 +/- 2% decrease), Shigella sonnei (53 +/- 13% decrease), Shigella flexneri (45 +/- 5% decrease), and enteroinvasive Escherichia coli (57 +/- 8% decrease). This decrease was specific for the HLA B27-transfected L cells and was not observed in the other B allele transfectants. The decreased invasion in the HLA-B27 transfectants is not the result of either altered endogenous mouse class I expression as a result of human class I transfection or increased intracellular bacterial killing within the B27 transfectants. There was an inverse relationship between the amount of surface expression of HLA-B27, as measured by FACS, and the degree of invasion. Blocking of surface B27 Ag with anti-B27 mAb augmented bacterial invasion in the B27 transfectants. These studies demonstrate a novel bacterial-B27 interaction that may have relevance to the pathogenesis of B27-related arthritis.
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PMID:HLA-B27 expression modulates gram-negative bacterial invasion into transfected L cells. 158 45

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

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

We investigated IgG, IgA and IgM class specific antibodies to five bacterial (Klebsiella pneumoniae, Escherichia coli, Salmonella enteritidis, Salmonella typhimurium and Shigella flexneri) lipopolysaccharides (LPS) by enzyme-linked immunosorbent assay in 144 Japanese patients with ankylosing spondylitis (AS). AS patients had significantly elevated IgA antibodies to K. pneumoniae LPS, Salmonella enteritidis LPS and Salmonella typhimurium LPS; however, there was no correlation between antibody level to LPS and acute-phase reactants, erythrocyte sedimentation rate and serum C-reactive protein.
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PMID:Antibodies against bacterial lipopolysaccharides in Japanese patients with ankylosing spondylitis. 915 47

Major developments have taken place to further our understanding of the relationship between genetics and the environment in the pathogenesis of rheumatic disorders. The association between HLA markers and human disease is becoming clearer. For instance, HLA-DRW4 frequently occurs in patients with rheumatoid disease, and penicillamine and gold toxicity are seen most often in patients with HLA-DRW2 or DRW3. Antisera to B alloantigens help define the genetic differences between systemic lupus erythematosus and rheumatoid arthritis. As yet, the most dramatic link is that between HLA-B27 and primary ankylosing spondylitis. This same antigen is related, to varying degrees, with other members of the seronegative spondylarthritides and there is strong evidence that this association is related to HLA-B27, itself, rather than an associated disease gene. Nevertheless, some data refute a single gene theory. We are just beginning to learn more about interactions between different genes on the sixth chromosome and genes on other chromosomes.The sex ratio of the spondylarthritides is now better defined. Sacroiliitis may have a comparable sex distribution although females have more peripheral joint disease and males have greater spinal involvement. Unfortunately, the explanation for these differences remains elusive.The specific infective agents related to the development of rheumatic disorders are becoming clarified. Chlamydia, Salmonella, Yersinia and Shigella flexneri types 1b and 2a are arthritogenic, while Shigella sonnei appears not to cause disease. Although the Reiter syndrome is now considered a chronic disease, the reason for remissions and relapses remains unclear.
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PMID:The relationship between genetics and environment in the pathogenesis of rheumatic diseases. 1874 70