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)

Among the numerous autoimmune diseases associated with various HLA alleles, the one with the highest relative risk so far reported has been ankylosing spondylitis with HLA-B27. To examine this relationship more directly, we have cloned the gene encoding the HLA-B27 antigen and determined its complete DNA sequence. Comparison of the HLA-B27 sequence with that of the allelic HLA-B27 shows a high level of homology. Mutations are distributed evenly between exons and introns. Exon 1 and intron 1 are the most divergent ones, and the degree of divergence distinctly declines towards the 3' end. The HLA-B57 gene when transfected into murine L cells is expressed on the cell surface and reacts with a panel of monoclonal antibodies directed against monomorphic and polymorphic determinants associated with HLA-B27 antigen. The isolation of this gene allows for the first time a search for structural features which make the HLA-B27 antigen a high risk genetic factor for a group of rheumatoid disorders, in particular ankylosing spondylitis.
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PMID:Organization, sequence and expression of the HLA-B27 gene: a molecular approach to analyze HLA and disease associations. 391 16

Using a two hit theory of x-irradiation damage to DNA in ankylosing spondylitis treated patients (in a course of 10 treatments), I have found that a dose squared theory can approximately yield results which are in agreement with observation. The first hit inactivates premutational repair, while the second hit causes a mutation in an operator region which controls cell division. And average value of the immunological efficiency is used for the removal of incipient tumor cells.
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PMID:X-radiation carcinogenesis in humans. 399 97

The effect of heat-aggregated human gamma globulin (aggFII) on the induction of in vitro lymphocyte transformation, measured by the uptake of tritiated thymidine into newly synthesized DNA, was studied with peripheral blood lymphocytes derived from 12 patients with rheumatoid arthritis (RA), six with ankylosing spondylitis (AS), two with systemic lupus erythematosus (SLE), and seven normal subjects. It was found that 200 mug aggFII induced significant transformation of the lymphocytes of eight patients with RA, five with AS, one with SLE, and one normal subject. Neither deaggregated FII nor heat-aggregated human serum albumin induced significant transformation of the lymphocytes of any subject tested. A source of complement appeared necessary to support aggFII-induced blastogenesis, since enhanced transformation occurred only in the presence of fresh plasma. Heat-inactivated plasma and fetal calf serum (FCS), and FCS devoid of hemolytic complement, failed to support enhanced blastogenesis in the presence of aggFII. Since substrates similar to those employed in these studies are present in vivo in the rheumatoid joint, it is suggested that aggFII may enhance intra-articular lymphocyte transformation in subjects with RA.
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PMID:Enhancement of human lymphocyte transformation by aggregated human gamma globulin. 413 Nov 62

The purpose of the study was to estimate the relative frequency of the known HLA-B27 subtypes among HLA-B27 positive Chukot natives. Using oligotyping of the polymerase chain reaction amplified second and third exons of the HLA-B27 gene in 86 DNA samples from HLA-27 positive individuals were success-fully typed. All had HLA-B*2705, including nine patients with ankylosing spondylitis and Reiter's syndrome, except for one Eskimo who had HLA-B*2702. None had HLA-B*2704, a frequent subtype in Orientals. Considering the HLA-B27 subtypes, the Chukot population groups are genetically more closely related to Caucasians than to Orientals.
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PMID:[DNA typing of allelic variants of HLA-B27: HLA-B*2705 is the predominant allele of the aboriginal population of the Chukot peninsula (Eskimos and Chukchi)]. 789 30

Genetic analysis of complex diseases is undergoing a paradigm shift as the DNA technology and computational resources for analysis become more precise. In this review we compare the old paradigm for genetic disease analysis with the new, more powerful and efficient methods, which rely on the application of genetically linked markers. To illustrate the utility of the new approach, we apply it in the study of ankylosing spondylitis.
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PMID:Major gene analysis for diseases and disorders of complex etiology. 853 1

The term spondyloarthropathy (SpA) describes and defines a group of related inflammatory joint disease that share characteristic clinical features and a unique association with the major histocompatibility complex class I molecule HLA-B27. Five subgroups can be differentiated: ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated SpA. The sacroiliac joints are centrally involved in the SpA, most clearly and pathognomonic in ankylosing spondylitis, in which most patients are affected early in the disease. Overcoming some of the diagnostic difficulties of early sacroiliitis, dynamic magnetic resonance imaging was shown to visualize both acute and chronic changes in the sacroiliac joints. The inflammation in the sacroiliac joints in patients with SpA was recently examined in more detail; using immunohistology and in situ hybridrization, T cells, macrophages, and various cytokines were found in infiltrates. Biopsy specimens were obtained under guided computed tomography, and in the same study, intra-articular corticosteroid treatment was successfully undertaken. Further investigation of such biopsy specimens showed the absence of DNA of reactive arthritis-associated bacteria. The pathogenesis of the SpA and the reason for the tropism for the sacroiliac joints is still obscure. The nature of the relation of the genetic background of SpA to initially triggering bacterial infections remains to be established. In chronic disease, autoimmune mechanisms might be more important.
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PMID:The sacroiliac joint in the spondyloarthropathies. 886 78

The aim of the study was to investigate the role of HLA-B27 subtypes in development of ankylosing spondylitis and other seronegative spondylarthropathies. Using oligotyping techniques we studied native DNA of 219 HLA-B27 positive natives: 88 Chukotka residents and 131 Mordovians (Russian Ugro-Finnish population). Only subtypes HLA-B*2705 and B*2702 were revealed. A dominant subtype of HLA-B27 among the natives was HLA-B*2705: 99% among residents of Chukotka and 86% among Mordovians. It was established that among spondylarthropathic patients the frequency of B*2705 does not differ from its incidence in the studied populations. The data support the suggestion that several B27 subtypes and common genetic determinant of B27 gene may be involved in pathogenesis of spondylarthropathy.
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PMID:[Spondyloarthropathies and HLA-B27 subtypes in the populations of the Russian North]. 923 54

Although a number of reports have now described an association between polymorphism of the LMP2 gene and disease phenotype in HLA-B27 positive individuals with ankylosing spondylitis (AS), some describe associations with acute anterior uveitis, others with juvenile onset disease, and one report provides no association. A recent study describes yet a further association with disease severity in patients with juvenile rheumatoid arthritis. We therefore hypothesized that the discrepant findings in adult disease may be a reflection of an underlying association with disease severity. Our study population consisted of 100 HLA-B27 positive Caucasians with AS of ten or more years duration. Clinical assessment of disease severity was based on a metrology index scoring five measurements, the modified health assessment questionnaire for the spondyloarthropathies, and a disease activity index consisting of a visual analog scale to score the amount of pain, stiffness and fatigue. LMP2 genotypes were assigned following polymerase chain reaction amplification from genomic DNA and restriction enzyme digestion with CfoI. Despite confirmation of a significantly higher prevalence of the LMP2 BB genotype in AAU positive (66.0%) versus AAU negative (45.2%) patients (P < 0.05), we observed no association between LMP2 genotypes and any of the indices of disease severity. Furthermore, although a significant association was noted between the presence of peripheral synovitis and the functional index score (P < 0.05), a history of AAU was not associated with more severe disease. Our data is thus internally consistent in demonstrating no association between LMP2 genotypes and either disease severity or peripheral arthritis, and supports the notion that polymorphism of LMP2 primarily influences the development of AAU and not some other phenotype of AS.
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PMID:Polymorphism of the LMP2 gene and disease phenotype in ankylosing spondylitis: no association with disease severity. 934 40

For evaluation of specificity and sensitivity of flowcytometric determination of HLA-B27 antigen, we determined the HLA-B27 on lymphocytes using HLA-B27 monoclonal antibody by flow cytometer. Data were compared to those by conventional Terasaki microlymphocytoxicity test and DNA genotyping Polymerase Chain Reaction (PCR) method. One hundred and ninety four patients with various forms of arthritis were included in this study. Forty one of them were HLA-B27 positive, confirmed by three methods concomitantly with complete accordance. None of serological B27 negative, B7 CREG positive cells were found to be flowcytometric fluorescence positive. Furthermore, there was no significant difference of B27 intensity between different B27 DNA subtypes, nor was there any difference between primary ankylosing spondylitis (AS) and other secondary spondylitis patients as measured by mean channel of fluorescence. It is suggested that flowcytometric measurement of HLA-B27 antigen is a rapid and reliable method for HLA-B27 determination.
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PMID:Two color analysis of HLA-B27 antigen by flow cytometer--a comparative study by conventional microlymphocytotoxicity, DNA genotyping polymerase chain reaction and flow cytometric measurement. 940 59

We report the complete coding sequence of a new HLA-B27 subtype, B*2712, which was found in a Caucasian Spanish family within the chromosome A2-Cw2-B*2712-DR15-DQ6. B*2712 was first detected as a segregating B blank Bw6-associated antigen. Extensive serologic analysis demonstrated that this new B27 subtype was not recognised by any of the B27-monospecific antibodies, giving positive reactions only with some monoclonal reagents against B40 or B27,40. Sequencing analysis showed a high similarity with B*2708, only differing in three clustered amino acid residues at positions 69 to 71 located in the alpha helix of the alpha1 domain. Residues 69 and 71 point towards the T-cell receptor, while amino acid 70 points to the antigen binding site. Loss of the conserved structure of pocket B as well as the differentiated pocket F configuration suggests that B*2712 does not confer ankylosing spondylitis susceptibility. Misleading serologic definition supports the usefulness of DNA-typing methods to complement HLA class I typing.
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PMID:Complete coding sequence of HLA-B*2712: a serologic B27-negative antigen associated to Bw6. 958 13


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