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)

Functional dissection of HLA-B27 subtypes using alloreactive or B27-restricted CTL has shown that the structurally related B*2704 and B*2706 are the most distant subtypes relative to the prototype B*2705. In particular, previous studies have failed to find anti-B*2705 CTL cross-reacting with B*2704 or B*2706. Such failure can be accounted for by the drastic effect on T cell recognition of the change at residue 152 in both subtypes relative to B*2705, as established with site-directed mutants. B*2704 and B*2706 are also related in ethnic distribution, as they are restricted to Orientals, jointly being the predominant HLA-B27 subtypes in this population. As far as it is known, there are no differences relative to B*2705 in their linkage to ankylosing spondylitis. In our study, 5 of 13 examined anti-B*2705 limiting dilution CTL lines from a particular HLA-B27- individual were shown to crossreact with B*2704, B*2706 or both. The monoclonal nature of this cross-reaction was established by cold target competition analysis. This result demonstrates that the apparent differences in T cell antigenicity among anti-B27 subtypes are strongly influenced by the responder individual, as the spectrum of clonal specificities in anti-B27 responses may show significant differences among unrelated responders. Fine specificity differences among the cross-reactive CTL allowed unambiguous functional distinction between B*2704 and B*2706. The molecular basis of such cross-reactivity was examined by correlating CTL reaction patterns with the structure of both subtypes, which differ only by two residues located in the beta-pleated sheet bottom of the peptide binding site, and with site-directed mutants mimicking HLA-B27 subtype polymorphism. The results suggest that: 1) distinct peptides are involved in the allospecific epitopes recognized by the various crossreactive CTL, and 2) B*2704, B*2706, and B*2705 differ in their peptide-presenting specificity, but can present some identical or structurally similar peptides.
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PMID:Peptide-presenting similarities among functionally distant HLA-B27 subtypes revealed by alloreactive T lymphocytes of unusual specificity. 137 Nov 37

The aim of this study was to investigate the contribution of the different B27 subtypes to ankylosing spondylitis (AS) susceptibility. The polymerase chain reaction (PCR) in combination with the sequence-specific oligonucleotide probes (SSOs) was used to analyse the polymorphism in exon 2 and 3 of HLA-B27 in two Asian groups with different genetic HLA structures: Indian (I) and Thai (T) populations. The same number of AS patients (45) and healthy B27 positive donors (n = 17) from both populations were analysed in order to ascertain the B27 subtypes. Three different findings can be concluded from this study: 1) B*2707 has been found to be associated with AS in both populations. This association has not been previously reported in either ethnic group. 2) B*2704 is strongly associated with AS in the Thai patients (91% in AS vs. 47% in C; RR = 11.5; EF = 0.83). In contrast, B*2704 was found with similar frequency in Asian Indians AS patients and controls (41% in AS vs. 41% in C.). 3) B*2706 was found overrepresented in control populations and absent in AS patients (0% in AS vs. 47% in C.; pc < 10(-6)) showing the maximum value of protective fraction (PF = 1). The B*2706 negative association with AS has not been previously described in other ethnic groups and could indicate a protective effect of this subtype on AS susceptibility. The B*2706 allele has two changes relative to B*2704 at residue 114 (His to Asp) and 116 (Asp to Tyr) in the pockets D/E. The importance that these differences can play in the pathogenesis of AS are discussed.
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PMID:HLA-B27 subtypes in Asian patients with ankylosing spondylitis. Evidence for new associations. 776 76

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

Linkage analysis of HLA haplotypes, HLA-B27 subtypes, and a 9.2-kb PvuII B7 restriction fragment length polymorphism (RFLP) (shown previously to be associated with peripheral arthritis in ankylosing spondylitis [AS]) in 115 relatives from 12 multiplex spondyloarthropathy (SNSA) and 2 B27-positive control families showed AS to be linked to HLA-B27 haplotypes. The RFLP segregated with HLA-A3- and HLA-A9-bearing haplotypes (lod score, 10.98; odds in favor of linkage, 9.2 x 10(10):1), although its linkage to AS or other SNSA per se was not seen. The association of HLA-A3/A9 with the RFLP was also seen in 52 AS patients and 92 controls, although no HLA-A, -B, -C, or -DR allele (other than HLA-B27) was significantly increased in frequency. The HLA-B27 subtype seen on all but one of the haplotypes studied was B*2705, the sole exception being HLA-B*2702. Although not ruling out a second HLA-A-linked gene influencing the clinical expression of AS, these data fail to support the role of a second MHC-associated gene in the pathogenesis of AS per se.
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PMID:HLA in ankylosing spondylitis: is HLA-B27 the only MHC gene involved in disease pathogenesis? 791 56

Five HLA-B27 subtypes, B*2701, B*2703, B*2704, B*2705, and B*2706, were tested for direct binding with twenty-six synthetic nonapeptides carrying the primary anchor residue motifs (combination of amino residues at positions 2 and 9) relevant to B*2705. The peptide sequences were derived from human HSP89 alpha, P53 and MBP. The alpha chains were immunospecifically isolated from LH (B*2701), CH (B*2703), WE1 (B*2704), BTB (B*2705), and LIE (B*2706) cells and their peptide binding was measured by the HLA class I alpha chain refolding assay. The data obtained indicated that the B27 subtypes tested can bind a common set of peptides carrying several different anchor residue motifs. The motifs, R-K and R-R, reported for B*2705 and a new motif H-R were accepted by B*2703, B*2704, and B*2706, but not by B*2701. However, other motifs, including known B*2702 and/or B*2705 motifs, R-H, R-L, R-A, and R-F, and a new motif found here, R-G, were apparently accepted by all B27 subtypes tested. The observed cross-peptide binding in the B27 subgroup is compatible with the so-called arthritogenic peptide hypothesis in the pathogenesis of ankylosing spondylitis.
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PMID:The peptide binding specificity of HLA-B27 subtypes. 803 27

It was the purpose of this study to better define the frequency of HLA-B27 subtypes and HLA class II alleles among indigenous populations from the eastern tip of the Chukotka Peninsula of Siberia, Russia, which have higher frequencies of HLA-B27 (40%) and spondyloarthropathies (2%) than Caucasian populations and test the hypothesis that these populations are more closely related to Orientals. Siberian Eskimos and Chukchi residing in four coastal villages on the Chukotka Peninsula inhabited by Siberian Eskimos and Chukchi people were examined using oligotyping of the polymerase-chain reaction-amplified second and third exons of the HLA-B27 gene. HLA-class II alleles (DRB1, DQA1 and DQB1) were similarly determined. Of 88 HLA-B27 positive individuals from these villages, all had HLA-B*2705, including the four patients with Reiter's syndrome and the five ankylosing spondylitis, except one Eskimo control who had HLA-B*2702. None had HLA-B*2704, a frequent subtype in Orientals. HLA-class II typing in 70 Siberian Eskimos and 71 Siberian coastal Chukchi revealed HLA-DRB1*0401, DRB1*0802, *0901 and *1402 to account for nearly all the DRB1 alleles found in this population, similar to what has been described in Eskimos in Alaska, but different from Chinese or native Americans in the U.S. The overwhelming majority of the individuals examined had HLA-DQB1*0301, similar to what has been observed in Native Americans. The Siberian Eskimos differed from the coastal Chukchi only in the occurrence of HLA-DRB1*0701, DQA1*0201, DQB1*0201 alleles, which occurred only in the former group. These data suggest that the Chukotka population is genetically more closely related to Caucasians and native Americans and less to other Oriental populations.
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PMID:HLA class II and HLA-B27 oligotyping in two Siberian native population groups. 883 47

B*2704 and B*2706 are closely related HLA-B27 subtypes of which the former but not the latter is associated to ankylosing spondylitis. Their peptide specificity relative to other disease-associated subtypes was analyzed by testing binding of self-peptides naturally presented by B*2705 or B*2702, and synthetic analogs, to B*2704, B*2706, and site-specific mutants mimicking their changes. Peptides with basic, aliphatic or aromatic C-terminal residues bound to B*2705 with similar affinity. In B*2704 C-terminal aliphatic/ aromatic residues were preferred. B*2706 discriminated drastically between polar and nonpolar C-terminal residues, showing strong preference for Leu and Phe, and less than B*2704 for basic and Tyr residues. Loss of single acidic charges (D > S77, D > Y116) increased preference for C-terminal Leu and Phe, but allowed efficient binding of peptides with basic residues or Tyr. Their gain (V > E152, H > D114) maintained wide C-terminal specificity, but severely impaired binding, presumably by disrupting interactions with internal peptide residues. This was compensated by Y116 in the double D114Y116 mutant. The specificity of B*2704 and B*2706 was explained only partially by the separate effects of single mutations, indicating that novel properties arise from concomitant changes at various positions. For instance, specificity of B*2706 for nonpolar C-terminal residues required simultaneous removal of Asp77 and Asp116. B*2706 differed from B*2705, B*2702, and B*2704 in its lower suitability for C-terminal Tyr, suggesting that this feature might be relevant for HLA-B27 association to spondyloarthropathy.
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PMID:Binding of peptides naturally presented by HLA-B27 to the differentially disease-associated B*2704 and B*2706 subtypes, and to mutants mimicking their polymorphism. 898 33

A possible mechanism for the pathogenesis of HLA-B27-associated spondyloarthropathies is that peptides from arthritogenic bacteria with homology to endogenous self-peptides presented by HLA-B27, including those derived from HLA-B27 itself, could elicit an autoimmune T-cell response upon infection. We report here that an undecamer corresponding to the polymorphic region of HLA-B27 spanning residues 169-179 is presented in vivo by the B*2701, B*2704 and B*2706 subtypes, but was not detected in the B*2703-bound peptide pool. This peptide binds to B*2705 in vitro with sufficient affinity to allow its natural presentation by this subtype, but it binds with low affinity to B*2703. In spite of homology of this peptide to proteins from arthritogenic bacteria, its binding specificity does not correlate with current evidence concerning association of HLA-B27 subtypes to ankylosing spondylitis, suggesting that presentation of this peptide is not the critical feature that determines linkage of HLA-B27 to this disease.
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PMID:HLA-B27 presents a peptide from a polymorphic region of its own molecule with homology to proteins from arthritogenic bacteria. 902 61

HLA-B27 is strongly associated with ankylosing spondylitis (AS) but the role of the HLA molecule itself is still unclear. In this study on Singapore Chinese, we have subtyped 50 B27 positive AS patients and 45 B27 positive normals and found that the B*2706 allele has a significant negative association with disease (p = 0.047). Together with recent data indicating the existence of AS "protective" B27 alleles, our data shows that the HLA molecule itself plays a crucial role in disease development.
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PMID:Possible protective role of HLA-B*2706 for ankylosing spondylitis. 902 69

HLA-B27 is strongly associated to ankylosing spondylitis (AS) and represents a family of eleven B27 alleles (B*2701-11). Our aim was to analyze the distribution of B27 subtypes by PCR/SSOP and genomic sequencing in a large group of populations (n = 17). 711 B27-positive samples from Caucasoid, Asian, African, Amerindian and Polynesian populations were selected to ascertain transracial gene mapping of the B27 subtypes. 476 of these were AS patients, chosen to investigate the contribution of B27 alleles to AS susceptibility. Some significant new findings have arisen from this study: 1) B*2705 was the predominant subtype in circumpolar and subarctic areas. B*2702 was found to be practically restricted to Caucasian populations, showing a higher frequency in Middle-East (Jews) and North Africa (Arabs/Berbers) groups. 2) B*2703 appears associated with AS in Western Africans. This is of remarkable interest since it was suggested that B*2703 would be negatively disease-associated. 3) Although B*2706 appears negatively associated with AS in Thais, we identified two patients from northern China carrying it. This may be a reflection of a disease heterogeneity and could indicate that more than one pathogenic agent can be involved in AS. B*2709 has been recently described as negatively associated with AS in Sardinians. The molecular changes His114Asp (B*2706) and Asp116His (B*2709) could modify the genetic susceptibility to AS.
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PMID:HLA-B27 polymorphism and worldwide susceptibility to ankylosing spondylitis. 906 66


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