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)

Patient HLA-B27 typing is widely performed as an aid to the diagnosis of several diseases, particularly ankylosing spondylitis. Typing by flow cytometry, using monoclonal antibodies, has been shown to be a potentially useful alternative to classical serology on account of its speed, simplicity and economy. However, we required a flow cytometry typing procedure that would accurately differentiate HLA-B27 (Bw4) from B2708 (Bw6) and not be confounded by other HLA-B7/B27 cross-reactive group antigens. Accordingly, we evaluated the simultaneous use of two monoclonal antibody preparations, ABC-m3-FITC (anti-B27 + weak B7)/BB7.1-PE (anti-B7) and FD705-FITC (anti-B27), by testing a highly selected panel of 62 reference lymphocytes containing examples of all HLA-B7/B27 cross-reactive group antigens, including: HLA-B42, B47, B48, B73, B703, B2702, B2705 and B2708. In addition, 268 whole blood samples from routine patient requests for B27-associated disease typing were tested in parallel with HLA-B typing using the standard complement-dependent microlymphocytoxicity test. The detailed specificity of the three monoclonal antibodies was established and the products of HLA-B*2702, B*2705 and B*2708 were found to be readily differentiated from each other and all other HLA-B7/B27 cross-reactive HLA-B antigens.
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PMID:Routine HLA-B27 typing by flow cytometry: differentiation of the products of HLA-B*2702, B*2705 and B*2708. 958 42

The HLA-B*27 group of alleles has been extensively studied due to the association of particular B*27 alleles with ankylosing spondylitis (AS). We describe here an HLA-B*27 allele (B*2712) encoding an antigen that lacks reactivity with B27 monoclonal antibodies (moabs) and alloantisera but reacts with some B40/B60 moabs and alloantisera and expresses the Bw6 public epitope. This allele was discovered by the segregation of an HLA-B allele undetectable by PCR-SSP within a Caucasian family from the British population referred for routine bone marrow transplant HLA typing and found in the haplotype A*29; B*2712; Cw*1203; DRB1*13; DQB1*0603. Serological typing showed a lack of reactivity with four B27 moabs and four alloantisera but positive reactivity with moabs and alloantisera specific for B40/B60 and Bw6 public epitopes. Subsequent sequencing showed the closest homology was with B*2708 with three mismatches in exon 2 at positions 204, 209 and 210. The intron 2 sequence was identical with other B*27 lineage alleles including a 2 base pair deletion at positions 95 and 96. The relationship between HLA-B*2712 and reported B60 associations with susceptibility to AS remains to be determined.
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PMID:Functional characterization and exon 2-intron 2-exon 3 gene sequence of HLA-B*2712 as found in a British family. 994 44

Previously, we reported a triplet repeat polymorphism in the transmembrane region within the MICA gene closely linked to HLA-B in a limited number of B27-positive Caucasian patients with ankylosing spondylitis (AS) (N = 48). In this study, we enrolled much more patients including some negative for B27, 162 AS subjects consisting of 140 B27-positive, and 22 B27-negative patients. The microsatellite allele consisting of 4 repetitions of (GCT/AGC) (A4 allele) was present at a significantly higher phenotype frequency in the patient group than in the ethnically matched control group (Pc < 0.000001). However, the frequency of the A4 allele was not significantly higher in the B27-positive and B27-negative patient groups, as compared to the B27-positive and B27-negative control groups, respectively. The higher phenotype frequency of the A4 allele in the patient group was supposed to be due to a strong linkage disequilibrium between the MICA and HLA-B genes. Thus, the possibility that the MICA gene is involved in the pathogenesis of AS can be excluded, supporting the hypothesis of a primary association of AS with HLA-B27.
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PMID:Triplet repeat polymorphism in the MICA gene in HLA-B27 positive and negative caucasian patients with ankylosing spondylitis. 995 31

In addition to HLA-B27, other genetic factors are thought to be involved in the pathogenesis of ankylosing spondylitis (AS). Because of the location of the TNF gene in the vicinity of the HLA-B locus, and the prominent role in inflammation of its product, we investigated the association between AS and two G to A transition polymorphisms located at position -238 and -376 in the promoter region of the TNF gene. The distribution of the TNF alleles was determined in 86 HLA-B27+ AS patients and 163 healthy controls. From the 86 AS patients, 33 suffered from acute anterior uveitis (AAU). No significant difference for the TNF-376 polymorphism in AS and healthy controls was observed. The frequency of the TNF-238A allele in HLA-B27+ AS patients was significantly decreased compared to random controls (p = 0.021). However, the frequency of the TNF-238A allele in HLA-B27+ AS patients was not significantly different from that observed in HLA-B27+ healthy individuals (p = 0.6). Assessment of association showed that the TNF-238G allele is in linkage disequilibrium with the HLA-B27 allele (delta = 0.053; P = 0.008). Therefore, we conclude that the association between TNF-238G and AS is secondary to the HLA-B27 gene and that TNF-238 and-TNF-376 alleles are not likely to be involved in the susceptibility to AS.
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PMID:Polymorphism within the tumor necrosis factor alpha (TNF) promoter region in patients with ankylosing spondylitis. 1002 81

We report a case of a 40-year-old male with psoriatic arthritis associated with ankylosing spondylitis. At the age of 34, the patient suffered pain in his hips, knees, ankles, neck and low back 3 years after the onset of psoriasis vulgaris. The hip pain gradually became severe despite the medical treatment and physical therapy. On admission, the skin lesion of diffuse erythematous plaques with scales was observed on the trunk and extremities. Motion of the spine was markedly limited. We also noted limitation of motion in the bilateral hips and remarkable gait disturbance. In laboratory findings, rheumatoid factor and HLA-B 27 antigen were negative. Radiographs of the cervical spine showed typical bamboo spine as seen in ankylosing spondylitis. Obliteration of the sacroiliac joints and joint space narrowing in the hips with reactive sclerosis were revealed on the pelvic film. Bilateral cementless total hip arthroplasty with adductor tenotomy resulted in complete pain relief and a marked improvement in gait function 18 months after surgery. The appropriate reconstructive surgery was extremely helpful to increase daily activities of the patient in this case.
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PMID:[A case of psoriatic arthritis associated with ankylosing spondylitis treated with bilateral total hip arthroplasty]. 1004 23

The objective of this study was to investigate TNF promoter region polymorphisms for association with susceptibility to ankylosing spondylitis (AS). The TNF -238 and -308 polymorphisms were genotyped in 306 English AS cases and 204 ethnically matched healthy B27-positive controls, and 96 southern German AS cases, 58 B27-positive and 251 B27-negative ethnically matched controls. Additionally, the TNF -376 polymorphism was genotyped in the southern German cases and controls. In the southern German AS patients a significant reduction in TNF -308.2 alleles was seen, compared with B27 positive controls (odds ratio 0.4, P = 0.03, 95% confidence interval 0.2-0.9), but no difference in allele frequencies was observed at TNF -238. Significant association between AS and both TNF -238 and TNF -308 was excluded in the English cases. These results confirm previous observations in the southern German population of association between TNF promoter region polymorphisms and AS, but the lack of association in the English population suggests that these polymorphisms themselves are unlikely to be directly involved. More likely, a second, non-HLA-B, MHC locus is involved in susceptibility to AS in these two populations.
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PMID:Interethnic studies of TNF polymorphisms confirm the likely presence of a second MHC susceptibility locus in ankylosing spondylitis. 1119 71

In this study the immunogenetic relationships among 141 unrelated HLA-B27+ patients with ankylosing spondylitis (AS) and 792 members of their families were studied. Two control groups, with at least one B27+ parent were used (families undergoing transplantation program and triplet families undergoing paternity testing). All subjects were typed for HLA-A and -B antigens by microlyphocytotoxity test (MLCT) on local typing trays. The frequency of HLA-A and -B alleles was equal in the all tested groups. The segregation of all tested genes was regular regarding to the total number of positive and negative siblings, while regarding to the sex of sibs was irregular for HLA-B27 and -B5 gene. The statistical significance (p < 0.05) was found when ratio between B27+ and B27- sons in AS group was compared with the same ration in control families. In AS group was detected statistical significant (p < 0.01) high number of B5+ than B5- daughters and statistical significant (p < 0.05) less number of B5+ sons. HLA-B21 was shown to be decreased among B27+ AS patients. A synergistic effect between additional HLA-B alleles and B27 was not observed. The distribution of B27 haplotypes in AS and control families was similar except for haplotype HLA-A10, B27 which was significant (p < 0.001) less present in AS families.
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PMID:[Immunogenetic study of the HLA system in families of patients with ankylosing spondylitis]. 1155 4

Spondyloarthropathies represent complex genetic diseases whose development is influenced by environmental factors. Estimates suggest that three to nine loci may be responsible for the majority of the genetic susceptibility to ankylosing spondylitis. The only susceptibility locus identified to date in multiple populations is HLA-B, where several HLA-B27 alleles (subtypes) are strongly associated with disease. Recent evidence implicates cytochrome P450 2D6 as a second locus, although its influence on overall risk appears small. Despite considerable efforts to define how HLA-B27 contributes to disease, its role remains enigmatic. Increasing evidence suggests it has effects that are unrelated to its physiologic function. The basis for this is unknown but may be a consequence of the unusual tendency of this allele to misfold.
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PMID:Predisposing factors in the spondyloarthropathies: new insights into the role of HLA-B27. 1156 72

Molecular mimicry is discussed as a possible mechanism that may contribute to the development of autoimmune diseases. It could also be involved in the differential association of the human major histocompatibility subtypes HLA-B(*)2705 and HLA-B(*)2709 with ankylosing spondylitis. These two subtypes differ only in residue 116 of the heavy chain (Asp in B(*)2705 and His in B(*)2709), but the reason for the differential disease association is not understood. Using x-ray crystallography, we show here that the viral peptide pLMP2 (RRRWRRLTV, derived from latent membrane protein 2 (residues 236-244) of Epstein-Barr virus) is presented by the B(*)2705 and B(*)2709 molecules in two drastically deviating conformations. Extensive structural similarity between pLMP2 and the self-peptide pVIPR (RRKWRRWHL, derived from vasoactive intestinal peptide type 1 receptor (residues 400-408)) is observed only when the peptides are presented by B(*)2705 because of a salt bridge between Arg(5) of both peptides and the subtype-specific heavy chain residue Asp(116). Combined with functional studies using pLMP2/pVIPR-cross-reactive cytotoxic T cell lines and clones, together with target cells presenting these peptides or a modified peptide analogue, our results reveal that a pathogen-derived peptide can exhibit major histocompatibility complex class I subtype-dependent, drastically distinct binding modes. Furthermore, the results demonstrate that molecular mimicry between pLMP2 and pVIPR in the HLA-B27 context is an allele-dependent property.
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PMID:Allele-dependent similarity between viral and self-peptide presentation by HLA-B27 subtypes. 1553 60

Major histocompatibility complex (MHC) class I chain-related A (MICA) molecules deliver activating signals through the NKG2D receptor expressed on the surface of natural killer (NK), CD8alphabeta and gammadelta T cells, and the MICA gene is polymorphic. The recently described MICA amino acid substitution at position 129 (MICA-129) seems to affect its binding to NKG2D. We investigated whether this dimorphism (MICA-129met [methionine] and MICA-129val [valine]) is associated with susceptibility to ankylosing spondylitis (AS) in a cohort of Algerian patients stratified according to their HLAB27 status and the age of onset of the disease. DNA from 129 patients and 76 healthy individuals were analyzed to determine the HLA-B generic type as well as MICA-129 polymorphism. Statistical analysis revealed: (1) a weaker association between AS and HLA-B27 in Algerians than in that reported for European patients (63% versus 80-90%), suggesting a possible influence of other genetic/environmental determinants in the studied population and (2) an association between MICA-129 met/met genotype and juvenile AS (p = 0.02) independent of HLA-B27 status. These data suggest a potential role for a functionally relevant MICA gene polymorphism in autoimmune/inflammatory disease susceptibility.
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PMID:Early-onset ankylosing spondylitis is associated with a functional MICA polymorphism. 1638 47


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