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)

One hundred and twelve well-studied patients with a prior diagnosis of juvenile rheumatoid arthritis were differentiated into seven clinically distinct subgroups, including a group in whom recognizable ankylosing spondylitis had developed by time of follow-up. An apparent increased prevalence of HLA-B27 in the entire series (26%) was clearly related to its increased prevalence in only two subgroups: patients whose disease had progressed to overt ankylosing spondylitis (five of five patients) and boys with pauciarticular arthritis whose disease would be consistent with early ankylosing spondylitis (11 of 18 patients). There were no significant associations of B27 with systemic onset JRA, polyarticular JRA, pauciarticular JRA in girls, or JRA with chronic iridocyclitis. The only other significant alterations found were increased prevalences of HLA-A2 and HLA-BW15 in patients with polyarticular disease without identifiable rheumatoid factor. This study emphasizes that the clinical disorders included under the category of juvenile rheumatoid arthritis represent more than a single disease and that this heterogeneity must be considered in interpreting studies such as those of histocompatibility typing.
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PMID:Histocompatibility antigens in childhood-onset arthritis. 127 Nov 90

The importance of HLA-B27 in the pathogenesis of ankylosing spondylitis is uncertain: current evidence favours a role for the B27 molecule itself. The possibility that quantitative differences in HLA-B27 expression may exist between patients with ankylosing spondylitis, family members, and control subjects positive for B27 was examined using appropriate monoclonal antibodies, flow cytometry, and a 'model lymphocyte' coated with a known number of mouse immunoglobulin binding sites. No differences were found between the groups. HLA-A2, examined for comparison, was expressed in greater amounts than HLA-B27, but each contributed only 10-20% of the total class I antigens. Homozygotes expressed twice the amount of antigen expressed by heterozygotes. Synovial lymphocytes expressed more class I antigens than peripheral lymphocytes.
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PMID:Measurement of HLA class I expression in ankylosing spondylitis. 144 27

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

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

The HLA class I molecules identified serologically as HLA-B27 are highly associated with ankylosing spondylitis and related human disorders. All known HLA-B27 amino acid sequences contain a cysteine residue at position 67; no other published HLA class I sequence contains a cysteine within the hypervariable region of the alpha 1 domain, which extends from amino acid residues 63-84. To investigate the role of this cysteine residue in the antigenic structure of HLA-B27, we isolated a genomic clone encoding a molecule of the HLA-B27.1 subtype and performed oligonucleotide-directed mutagenesis to convert the cysteine at position 67 to a tyrosine. When transfected into mouse L cells, both the wild-type and Cys67----Tyr67 mutant B27 genes directed the synthesis and surface expression of molecules reactive with the monomorphic anti-HLA class I antibody W6/32. However, only the L cells transfected with the wild-type B27 gene reacted with the anti-B27 antibody ME1; L cells transfected with the mutant B27 were completely unreactive with this antibody. Experiments with hybrid exons created from the HLA-B27 and HLA-A2 genes yielded results consistent with the mapping of the ME1 epitope to the B27 alpha 1 domain. A second anti-B27 antibody, GS145.2, also showed markedly reduced binding to the Cys67----Tyr67 mutant. These studies document the importance of the unique Cys67 residue in the antigenic structure of HLA-B27.
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PMID:In vitro mutagenesis of HLA-B27. Substitution of an unpaired cysteine residue in the alpha 1 domain causes loss of antibody-defined epitopes. 245 90

One hundred and sixty-nine patients, 82 with acute anterior uveitis (AAU) only, 48 with AAU and ankylosing spondylitis (AS), and 39 with AS only were studied. The HLA antigen A2 was present in 44/82 AAU only, 31/48 AAU + AS, and 23/39 AS only. Where haplotype analysis was possible by virtue of family studies, A2 B27 was present in 7/16 AAU only, 9/15 AAU and AS and 14/29 AS only. These figures do not differ significantly from the expected values of control populations. Alpha-1-antitrypsin (alpha-1-AT) phenotypes were obtained on 30/82 AAU only, 29/48 AAU + AS, and 27/39 AS only patients. The MZ phenotype appeared in 8/86 patients tested; 4/30 with AAU only and 4/29 AAU + AS patients. This is higher than the expected value for control populations. Therefore, MZ alpha-1-AT phenotype but not HLA-A2 appears increased in patients with AAU.
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PMID:Genetic markers for acute anterior uveitis. 660 43

We studied 175 consecutive patients with ankylosing spondylitis (AS) to define the genetic characteristics of those patients who had associated acute anterior uveitis (AAU). The first 131 patients were tested for HLA antigens of the A and B loci, and the remaining 44 patients were typed only for HLA-B27. AAU was significantly more common in B27 positive patients, occurring in 40 of 144 B27 positive (27.7%) and in only 3 of 31 B27 negative patients (9.7%) (p less than 0.05). Among the B27 positive AS patients, AAU occurred in 24 of 68 patients (35%) who also possessed HLA-A2 and in only 5 of 35 patients (14%) who lacked A2 (p less than 0.025). An independent association of AAU with A2 could not be shown. In the absence of evidence of linkage disequilibrium between A2 and B27 in the general population, the data suggest that the presence of A2 in B27 positive AS patients enhances the risk of AAU above that associated with B27 alone, and that other MHC-linked genetic factors, in addition to B27, are associated with susceptibility to AAU in AS patients.
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PMID:Association of HLA-A2 with uveitis in HLA-B27 positive patients with ankylosing spondylitis. 719 16

The histocompatibility antigens were determined in 170 normal Chinese by a modified micro-lymphocytotoxicity test of Terasaki using 26 typing sera obtained from Behring Laboratories and Stanford University, and the data were compared with those obtained from 36 systemic lupus erythematosus, 30 rheumatoid arthritis, 17 ankylosing spondylitis as well as 45 leprosy patients. In normal individuals HLA-A2,A11 and A9 were dominant in locus A, the frequency were 42.35%, 41.76% and 32.35% respectively. HLA-Bw17, B13 and B5 were dominant in locus B, the frequency were 55.29%, 19.41% and 14.70% respectively. In systemic lupus erythematosus, the frequency of B8, Bw38 and A3 were slightly higher than normal (relative risk > 2); the frequency of Bw21 and B7 were little lower (risk of Bw21 < 0.5, frequency of B7 > 5% in normals but none in patients). In rheumatoid arthritis, the frequency of A28 and A10 (Aw25+26) were slightly lower than normal (risk < 0.5). In ankylosing spondylitis, the frequency of B27 was extremely high (risk = 44.92), Aw24 was also rather high (risk > 2); the frequency of B5, Bw35 and A10 (Aw25+26) was low (risk < 0.5), Bw15 and Bw21 > 5% in normals but none in patients. In leprosy, the frequency of B18 was relatively high (risk > 2); A3, Aw30+31+32, B27 and Bw35 were somewhat low (risk < 0.5). Because of the small sample size, however, the differences were not significant by Chi square analysis except the high frequency of B27 in ankylosing spondylitis (corrected P < 0.001).
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PMID:[Tissue typing of blood lymphocytes in normal Chinese and diseases (author's transl)]. 744 26

The expression of serologic HLA-B27 epitopes on leukocytes of patients with reactive arthritis or ankylosing spondylitis has been shown to be modified in the course of the disease. The purpose of this work was to study whether phagocytosis of arthritis-triggering microbes in vitro alters the expression of HLA-B27 molecules on human antigen-presenting cells and to characterize the underlying mechanisms. Human monocytes and HLA-B27- or HLA-A2-transfected human U-937 cells were exposed to Yersinia enterocolitica serotype O:3. The expression of different epitopes of HLA-B27 was monitored by using immunofluorescence, and their synthesis was determined by quantitative immunoprecipitation. Our results show that phagocytosis of Y. enterocolitica serotype O:3 changed the expression of serological HLA-B27 epitopes. This was due to the reduced synthesis of HLA-B27 molecules. The expression of especially the epitopes which depend on the presence of peptides in the antigen-binding groove was changed. The expression of the ME1 epitope, which has been shown to be important for T-cell recognition in patients with reactive arthritis, was decreased. Down-regulation of epitopes important for the T-cell recognition may impair the elimination of arthritis-triggering microbes and lead to persistent infection. In addition, Y. enterocolitica serotype O:3 seemed to alter the repertoire of peptides presented by the HLA-B27 molecules on human monocytes. This may have a role in the pathogenesis of reactive arthritis via an autoimmune mechanism.
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PMID:Yersinia enterocolitica serotype O:3 alters the expression of serologic HLA-B27 epitopes on human monocytes. 916 32

Juvenile arthritis (JA) is a term that covers a number of different disease entities, of which only three present with significant Human Leukocyte Antigen (HLA) associations. (1) Pauciarticular JA with late onset and a strong male proponderance is associated with HLA-B27 and represents the group of juvenile spondyloarthropathies related to adult ankylosing spondylitis. (2) Early onset pauciarticular JA with a preponderance of females and a frequent occurance of chronic iridocyclitis and the frequent presence of anti-nuclear antibodies is associated with alleles from three different regions of the HLA system: HLA-A2, which shows a very strong correlation with early age of onset; DR8, DR11 and DR12 as well as DQA1*0401, *0501, *0601 and finally DPB1*0201. These alleles show no linkage disequilibrium in the control population. (3) Rheumatoid factor positive polyarticular JA is associated, as is adult rheumatoid arthritis, with DR4. Concerning the possible mechanisms of the immunopathogenesis, it is speculated that the normal function of HLA molecules, namely the presentation of antigenic peptides, plays a major role. Data collected on HLA associations in early onset pauciarticular JA have been interpreted as indicating that alleles of the DQA1 locus (*0401, *0501, *0601) are probably responsible for presenting the hypothetical arthritogenic peptides. It is speculated that the pathogenic process includes the presentation of HLA-A2 or HLA-DPB1*0201 derived peptides presented by DQ molecules. It is clearly stated that typing for HLA alleles has very little or no importance for clinical diagnosis and prognosis.
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PMID:Juvenile arthritis: genetic update. 989 94


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