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)

HLA/Bf haplotypes were examined in a large three-generation Newfoundland family with a high incidence of Graves' disease. In that family Graves' disease was inherited in association with the haplotype HLA Aw24, Bw39 in some instances and with HLA B8-containing haplotypes in other instances. As all seven members of the family who suffered from Graves' disease were homozygous for the Bf S allele, the study for Bf was uninformative. However, the examination of other HLA/Bf haplotypes disclosed some interesting associations. One-hundred-and-five out of 168 HLA-A, -B, -Bf haplotypes were Bf S. Although numerically deviant, no unusual HLA B/Bf associations were observed. Bf F entered the family only once. A new finding is the association between HLA B27 and Bf S1; the haplotype entered the family once and was passed on to eight family members over three generations. Bf S1 was previously reported in association with HLA B12 or W21. None of these family members had ankylosing spondylitis. The Bf allele F1 entered the family three times, always in association with HLA B18.
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PMID:HLA/Bf haplotypes in a Newfoundland family. 58 Dec 40

In studies of antigenic peptide presentation, we have found a healthy volunteer whose lymphoblastoid cells were unable to present three different virus-derived epitopes to cytotoxic T lymphocytes (CTL) despite expressing the correct restricting HLA-B27 molecules on the cell surface. B cell lines were established from other members of the donor's family, including individuals suffering from ankylosing spondylitis and related diseases, and were tested for their ability to function as target cells in the same assay. None of the eight B cell lines that expressed HLA-B27 presented a known peptide epitope to CTL. However, cells from a family member that expressed HLA-B8 could present an epitope peptide restricted by that molecule. The B27 molecule in this family proved to be the B2702 subtype on isoelectric focusing gels, appearing in exactly the same position as B2702 from other cell lines that did present the peptide. To exclude mutations resulting in noncharged amino acid substitutions, cDNA coding for B2702 was cloned from the proband's cell line and sequenced. No coding changes were found. The cloned cDNA was transfected into HLA-A- and B-negative HMy/C1R cells, and the B2702 molecules generated in this environment rendered these cells, after incubation with peptide, susceptible to lysis by peptide-specific CTL. These data are compatible with the presence of a factor(s), possibly HLA linked, interfering with antigen presentation by otherwise normal B2702 molecules in this family.
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PMID:Genetic modulation of antigen presentation by HLA-B27 molecules. 137 Jun 80

The strongest reported association between a class I HLA allele and disease is that of HLA-B27 with ankylosing spondylitis (AS). However, it has not been shown whether B27 is the gene that predisposes to the development of AS or if it is merely linked with the disease-susceptibility locus. Furthermore, if B27 itself is the disease-susceptibility gene, there may be epistatic loci that also contribute to the development of AS or modify its clinical manifestation. A class I HLA 9.2-kb Pvu II restriction fragment was recently identified, which, when present in a B27-positive individual, further increased the relative risk for developing AS (from 119 to 297). This study was therefore designed to confirm the association between AS and this restriction fragment length polymorphism (RFLP) and to map the location of this fragment in the genome. The data presented here suggest that the class I HLA 9.2-kb Pvu II RFLP represents a Pvu II polymorphism at the 5' end of the HLA-A locus that is tightly linked with both HLA-A3 and A9 alleles. However, there is no association between this RFLP and AS in a population of patients living in Baltimore.
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PMID:Characterization of the class I HLA 9.2-kb PVU II restriction fragment length polymorphism. Linkage to HLA-A and lack of disease association. 256 35

We examined the distribution of non-B27 alleles of the HLA-B locus among B27+ patients with ankylosing spondylitis (AS), to detect any additional HLA-B locus allele(s) that may act in conjunction with B27 to increase susceptibility to AS. HLA-Bw60 (or B40 when the Bw60,61 split of B40 was not typed for) was shown to be increased among B27+ AS patients in each of 5 independent data sets. This increase was statistically significant in 4 of the 5 data sets studied, and the overall significance was P less than 0.00001. Susceptibility to AS in B27+ individuals was further increased by a factor of approximately 3 when Bw60 was also present. The distribution of HLA-A alleles on the B27-bearing haplotypes in AS patients was not significantly different from that in normal controls. On the other hand, the distribution of HLA-A alleles on Bw60-bearing haplotypes was significantly different from the distribution of A alleles on Bw60 haplotypes in the general population (P less than 0.0005). Bw60 was not increased in B27- patients with AS. A dominant mode of inheritance generally fits AS; however, our sib pair analysis indicates that the B27,Bw60 disease subgroup follows a more recessive mode of inheritance.
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PMID:HLA-Bw60 increases susceptibility to ankylosing spondylitis in HLA-B27+ patients. 199 28

Isoelectric focusing gel electrophoresis was used to look for variant HLA molecules in five patients with HLA-B27 negative ankylosing spondylitis (AS). The isoelectric points of the HLA-A and B antigens from these patients and HLA paired controls were identical. This implies that the HLA-A and B antigens from the patients with AS and the controls are similar. Gene conversion of a nucleotide sequence from a B27 positive gene is thus unlikely to be the explanation for the existence of AS in patients who are HLA-B27 negative by alloantisera typing.
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PMID:Ankylosing spondylitis without B27: no evidence for gene conversion. 326 96

In a consecutive case study 231 patients with Crohn's disease were investigated for ankylosing spondylitis (AS) and HLA-A, B, C, DR antigen association. Eighteen patients (7.8%) had definite AS according to the New York criteria; 13 (72%) were HLA-B27 positive. The phenotype B27,B44 was seen in 8 patients (44%) compared to only 3 (1%) of 300 controls (p less than 10(-7), and 1 (0.5%) of 213 patients with Crohn's disease without AS (p less than 10(-7). We conclude that patients with the phenotype B27,B44 are highly at risk (relative risk = 68.8) for the common manifestation of Crohn's disease and AS.
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PMID:HLA antigens in ankylosing spondylitis associated with Crohn's disease. Increased frequency of the HLA phenotype B27,B44. 326 50

Antigen HLA-B27 is a high-risk genetic factor with respect to a group of rheumatoid disorders, especially ankylosing spondylitis. A cDNA library was constructed from an autozygous B-cell line expressing HLA-B27, HLA-Cw1, and the previously cloned HLA-A2 antigen. Clones detected with an HLA probe were isolated and sorted into homology groups by differential hybridization and restriction maps. Nucleotide sequencing allowed the unambiguous assignment of cDNAs to HLA-A, -B, and -C loci. The HLA-B27 mRNA has the structural features and the codon variability typical of an HLA class I transcript but it specifies two uncommon amino acid replacements: a cysteine in position 67 and a serine in position 131. The latter substitution may have functional consequences, because it occurs in a conserved region and at a position invariably occupied by a species-specific arginine in humans and lysine in mice. The availability of the complete sequence of HLA-B27 and of the partial sequence of HLA-Cw1 allows the recognition of locus-specific sequence markers, particularly, but not exclusively, in the transmembrane and cytoplasmic domains.
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PMID:Complete sequence of HLA-B27 cDNA identified through the characterization of structural markers unique to the HLA-A, -B, and -C allelic series. 348 86

Ninety percent of individuals with ankylosing spondylitis (AS) express HLA-B27. To determine if HLA-B27 coding sequences from normal vs AS individuals show differences that might relate to the etiology of the disease, the gene coding for this allele was cloned from three different partial genomic libraries. These libraries were made with DNA from three different cell lines expressing HLA-B27: MRWC (HLA-B27, 14), obtained from an AS patient; KCA (HLA-B27, w44), obtained from a known normal individual; and MVL (HLA-B27, 27), a homozygous consanguineous cell line of unknown origin. To increase the number of clones coding for the HLA-B locus, partial libraries were made using a complete Eco RI digestion of genomic DNA in the lambda vector 607. The libraries were screened with two probes; one probe hybridizes to all HLA-A, B, C class I genes, and the other to a small subpopulation of class I genes, including the B locus. DNA from clones hybridizing with both probes was transfected into murine L cells. Cell surface expression of HLA-B27 on murine L cells was detected with a polymorphic monoclonal antibody (ME1) specific for HLA-B27, 7, 22. DNA from those clones positive for HLA-B27 by transfection was subcloned into the Xba I site of M13mp18 and the DNA sequence for exons 2 through 4 (encoding domains alpha 1, alpha 2, and alpha 3) was determined by the dideoxy technique by using synthetic oligonucleotide primers or the M13 primer. The resulting sequences show no difference between HLA-B27 alpha 1, alpha 2, alpha 3 domains from a known AS patient and a known normal individual.
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PMID:Absence of polymorphism between HLA-B27 genomic exon sequences isolated from normal donors and ankylosing spondylitis patients. 348 55

The prevalence of HLA-A, B, C and DR antigens was determined and compared in 94 patients with reactive arthritis, 54 patients with ankylosing spondylitis (AS), 37 patients with inflammatory bowel disease (IBD) and in 1,010 apparently normal blood donors. The 185 patients all underwent ileocolonoscopy with biopsy of ileum, ileocecal valve and cecum. HLA-B27 was found elevated in the groups with reactive arthritis (48%, chi 2 = 82, p less than 0.0005) and the AS groups (78%, chi 2 = 157, p less than 0.0005), compared to healthy controls. HLA-Bw62 was significantly raised in the patients with reactive arthritis (34%, chi 2 = 73, p less than 0.0005) (particularly the HLA-B27 negatives (48%, chi 2 = 90, p less than 0.0005) and in the HLA-B27 negative patients with AS (25%, chi 2 = 5.5, p less than 0.02). This did not apply to the other patients with AS (4.7% NS). HLA-Bw62 could be associated with a specific clinical picture of asymmetrical pauciarticular arthritis, accompanied by enthesopathies and sacroiliitis classified as idiopathic reactive arthritis, especially when the disease is of enterogenic origin. The frequency of HLA-Bw62 was very high in patients with reactive arthritis and in patients with AS with active chronic (n = 39, 23%, chi 2 = 13, p less than 0.0005) and Crohn-like lesions (n = 14, 50%, chi 2 = 35, p less than 0.0005) on gut biopsy, normal in patients with acute lesions (n = 35, 11%, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HLA antigens in seronegative spondylarthropathies. Reactive arthritis and arthritis in ankylosing spondylitis: relation to gut inflammation. 349 33

Fifty one patients with ankylosing spondylitis (AS) were typed for HLA-A, B, C, DR, and DQ antigens. The antigen frequencies were compared with those of a normal population and with a B27 positive control group. All but one of the patients with AS were HLA-B27 positive. A positive linkage disequilibrium between Cw1, Cw2, DR1, and the B27 antigen was observed. Patients with AS showed a significant increase in DQw2 antigen compared with the B27 positive control group. No differences in antigenic frequencies were observed in patients having peripheral arthritis and patients with only axial involvement. Seven out of nine patients (78%) with an erosive peripheral arthritis were DR7 positive, suggesting that DR7 or genes closely linked could be related with a more aggressive peripheral joint involvement in patients with AS.
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PMID:HLA class II antigens (DR, DQ loci) and peripheral arthritis in ankylosing spondylitis. 366 36


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