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

The suggested relationship between Borrelia burgdorferi and seronegative spondyloarthropathies has been studied in 125 patients with ankylosing spondylitis (AS). IgG antibodies to Borrelia burgdorferi were present in 11 of 125 patients (8.8%) and in 25 of 125 controls (20%). No patient had clinical Lyme borreliosis. HLA-B27 status was known for 82 patients with AS. There was no difference between B27+ and B27 patients. This study provides no evidence that Borrelia burgdorferi is associated with AS.
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PMID:Is there any evidence for an association between ankylosing spondylitis and Borrelia burgdorferi infection? 159 80

Following a study reporting a fourfold increase in the occurrence of chronic otitis media in patients with ankylosing spondylitis, this prospective study examines this association with respect to severity, duration of disease, and acute phase in ankylosing spondylitis. Forty two consecutive patients with classical ankylosing spondylitis seen at the rheumatology clinic of a teaching hospital where the features of ankylosing spondylitis were recorded had an otological examination by an otolaryngologist. The occurrence of chronic otitis media (all categories) was 12/42 (29%). The acute phase serum markers (C reactive protein and IgG) were increased in patients with active or inactive chronic otitis media. Extra-articular manifestations were significantly more common in the chronic otitis media group than in those with no history of chronic otitis media. The results of this study suggest that chronic otitis media may be another extra-articular manifestation of ankylosing spondylitis. Alternative explanations, however, include similar aetiological factors for the two conditions or a previously unrecognised increased occurrence of HLA-B27 in patients with chronic otitis media.
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PMID:Chronic otitis media: a new extra-articular manifestation in ankylosing spondylitis? 161 33

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 phagocyte oxydative metabolism function was measured using chemiluminescence in microamounts of whole blood in 15 ankylosing spondylitis (AS) patients (10 were B27 positive), and in 17 controls. It was obtained from cells at rest, and following stimulation (latex, zymosan, fMLP), with luminol and lucigenin as amplifiers. The maximal light intensity was significantly higher (P less than 0.01) in AS compared to the controls in resting cells as well as in those after stimulation. There was no difference between HLA-B27 positive or negative AS patients. The increase in oxidative metabolism of the phagocyte system in AS was more evident in the luminol dependent assay, suggesting an activation of the myeloperoxydase system.
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PMID:The phagocyte oxidative metabolism function in ankylosing spondylitis. 166 42

We describe a rapid method of HLA class I typing using the polymerase chain reaction and oligonucleotide hybridisation that eliminates the requirements for viable lymphocytes and allows subtypes to be defined. We have used this to demonstrate that the predominant subtype of HLA-B27 in the Gambia, West Africa, is HLA-B*2703, which is very rare or absent in other racial groups. This subtype differs from the common Caucasian HLA-B27 subtypes in its recognition by cytotoxic T cells. We propose that HLA*B-2703, unlike other HLA-B27 subtypes, may not be associated with ankylosing spondylitis, thus accounting in part for the rarity of this condition in black populations.
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PMID:HLA class I typing by PCR: HLA-B27 and an African B27 subtype. 170 74

Although ankylosing spondylitis (AS) is known to be strongly associated with the class I major histocompatibility complex antigen HLA-B27, B27 is probably not the only genetic factor involved in the pathogenesis of AS. Because of the involvement of tumor necrosis factor (TNF) in cartilage damage and the localization of the TNF genes in the proximity of the HLA-B locus, we investigated the association between AS and TNF alleles. The frequencies of the restriction fragment length polymorphisms linked to the TNF genes were determined in 73 AS patients and 81 controls. No differences were observed between AS patients and controls with respect to the frequencies of the TNF restriction fragment length polymorphisms.
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PMID:Restriction fragment length polymorphism of the tumor necrosis factor region in patients with ankylosing spondylitis. 167 16

To further examine the role of the HLA-B27 antigen in the pathogenesis of disorders such as anterior uveitis and ankylosing spondylitis, we have measured the level of enhancement of this antigen on peripheral blood lymphocytes and compared it with that of the class I HLA antigens HLA-A2 and HLA-B7 following interferon treatment. We found that the level of enhancement of HLA-B7 was greater than that of HLA-A2 or -B7 following treatment by alpha or gamma interferon (p less than 0.002). Similarly, the level of enhancement of HLA-B7 was greater than that of HLA-A2 (p less than 0.002) (Mann Whitney U-test). A differential enhancement of HLA-B27 by lymphokines may be important in the pathogenesis of HLA-B27-related disorders.
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PMID:Differential enhancement of HLA-B27 by interferon. 168 84

HLA-B27 is strongly associated with susceptibility to ankylosing spondylitis and other spondyloarthropathies. Structural analysis of this antigen has revealed the existence of multiple variants, or subtypes, in human populations. The structural microheterogeneity of these subtypes deeply affects allospecific T cell recognition and most of it occurs at an spatial cluster within the peptide binding groove of the molecule. Many polymorphic residues whose combination is unique to HLA-B27 but is conserved among subtypes are clustered in a spatially separated site of the groove from that where most subtype polymorphism occurs. Site-directed mutagenesis and DNA-mediated gene transfer has been used to show that the positions that are polymorphic among subtypes are highly relevant for modulating T cell recognition, so that immunologically silent changes do not occur. These studies have also revealed an extremely high clonotypic diversity in the alloreactive response against HLA-B27. The structural basis for this diversity has been examined by sequencing the clonotypic T cell receptors. The analysis shows a certain bias in V beta gene segment usage, as well as other recurrent structural motives, among T cell receptor beta chains from HLA-B27-specific cytotoxic T cell clones.
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PMID:Structure and immune recognition of HLA-B27 antigens: implications for disease association. 170 18

Identification of several autoantibodies in serum samples from patients with ankylosing spondylitis or suspected ankylosing spondylitis is reported. Five antibodies associated with ankylosing spondylitis were identified by applying cytoimmunofluorescence and immunoblotting techniques to antigen pools from insect tissue. At least one of these antibodies was found in 82% of serum samples from patients with ankylosing spondylitis. A 36 kD drosophila antigen, which showed the most common and most dominant reaction, was further purified and isolated. Thirty two (34%) of the serum samples from 95 patients with definite ankylosing spondylitis and 12 (28%) of the serum samples from 43 patients with suspected ankylosing spondylitis reacted with this antigen. Antibodies purified from the 36 kD antigen reacted specifically with a 69 kD antigen present in separations of total protein preparations from human lymphocytes and HeLa cells. The 36 kD antibody was not found in 29 patients with rheumatoid arthritis nor in 38 apparently healthy controls. The prevalence of the 36 kD antibody was comparable in HLA-B27 positive and negative patients. In addition, the same immunoreaction was found in patients with so called 'seronegative' spondylarthropathies, particularly of the ankylosing spondylitis-type, suggesting that this antibody is specific for ankylosing spondylitis or other 'seronegative' spondylarthropathies with the typical clinical and radiological changes of ankylosing spondylitis.
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PMID:Ankylosing spondylitis: an autoimmune disease? 177 92


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