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)

The association of certain autoimmune diseases with HLA molecules is being refined through the use of sequence-specific oligonucleotide probes and amino acid sequencing, together with continuing elucidation of the functional features of HLA molecules derived from the milestone description by Bjorkman of the HLA molecular structure. The association of insulin-dependent diabetes mellitus and HLA began with weak associations of Class I antigens (B8 and B15) and progressed to Class II antigens (DR3 and DR4), then to subtypes of DR4 (Dw4, 10, and 14), and now to DQ molecules including the absence of aspartic acid at position 57 of the DQ beta chain and the presence of arginine at position 52 of the DQ alpha chain. In rheumatoid arthritis (RA) the HLA antigen association remains with certain Class II molecules of the DR series (DR4 and DR1) that share amino acid sequences with a restricted number of other DR antigens seen in RA, as well as a segment of the gp 110 protein of the Epstein-Barr virus. Although ankylosing spondylitis has a strong association with the Class I antigen B27, that association is not explained by any of the B27 subtypes defined by monoclonal antibodies, by the eight variable amino acids in B27 subtypes, or by the two unique amino acids on B27. The remarkable antibody cross-reactivity among lymphocytes bearing B27, a synthetic peptide sequence (63-84) of B27, and the 188-193 sequence of K. pneumoniae nitrogenase has provided strong support for molecular mimicry being an important mechanism in the association of HLA molecules with disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HLA molecules in autoimmune diseases. 163 34

A possible association between ankylosing spondylitis (AS) and multiple sclerosis (MS) has been suggested in whites. The authors describe the first report of the coexistence of AS and MS in a black patient. The clinical diagnosis of MS was further substantiated by the results of magnetic resonance imaging of the brain. The diagnosis of AS met the Rome as well as the New York criteria. The patient possessed HLA-B27; his complete HLA phenotype was Aw66, B27, Cw2, DR3, and DR5.
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PMID:Unusual occurrence of ankylosing spondylitis and multiple sclerosis in a black patient. 260 79

A patient is described who had insulin-dependent diabetes mellitus for 2 years, prior to developing rheumatoid arthritis and then subsequently ankylosing spondylitis and dermatomyositis. Diagnostic criteria for all diseases are fulfilled. HLA typing revealed the presence of HLA A2, A9, B8, B27, DR3 and DR4 antigens. The concomitant coexistence of diabetes mellitus, rheumatoid arthritis, ankylosing spondylitis and dermatomyositis appears to have occurred in an individual genetically susceptible to these diseases.
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PMID:Coexistence of rheumatoid arthritis, ankylosing spondylitis and dermatomyositis in a patient with diabetes mellitus and the associated linked HLA antigens. 336 34

We report six patients with coeliac disease in whom arthritis was prominent at diagnosis and who improved with dietary therapy. Joint pain preceded diagnosis by up to three years in five patients and 15 years in one patient. Joints most commonly involved were lumbar spine, hips, and knees (four cases). In three cases there were no bowel symptoms. All were seronegative. X-rays were abnormal in two cases. HLA-type A1, B8, DR3 was present in five and B27 in two patients. Circulating immune complexes showed no consistent pattern before or after treatment. Coeliac disease was diagnosed in all patients by jejunal biopsy, and joint symptoms in all responded to a gluten-free diet. Gluten challenge (for up to three weeks) failed to provoke arthritis in three patients tested. In a separate study of 160 treated coeliac patients attending regular follow up no arthritis attributable to coeliac disease and no ankylosing spondylitis was identified, though in a control group of 100 patients with Crohn's disease the expected incidence of seronegative polyarthritis (23%) and ankylosing spondylitis (5%) was found (p less than 0.01). Arthritis appears to be a rare manifestation of coeliac disease. This relationship may provide important clues to the role of gastrointestinal antigens in rheumatic diseases.
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PMID:Arthritis and coeliac disease. 387 79

Within the last 7 years, HLA and disease studies have made it clear that most of the diseases previously known to be HLA-A- or B-associated do in fact show stronger associations with HLA-D/DR antigens. This observation strengthens the assumption that Ir and/or Is determinants are responsible for these associations in agreement with the fact that many of these diseases are characterized by autoimmune phenomena. However, some diseases, ankylosing spondylitis in particular, still show stronger associations with HLA-ABC than with DR antigens. Among the conditions which have been shown to be HLA-associated more recently, four deserves special mention: (i) maternal immunization against the Zwa antigen because this is a good candidate for an antigen-specific Ir gene action; (ii) IgA deficiency in blood donors because this is a non-antigen-specific immunodeficiency; (iii) idiopathic hemochromatosis and (iv) congenital adrenal hyperplasia due to 21-OH deficiency because immune mechanisms are unlikely to be involved. HLA studies and new genetic methodology have significantly advanced our knowledge about the inheritance of some diseases. Thus, HLA-B27 or a B27-associated HLA factor confers a dominant susceptibility to ankylosing spondylitis. HLA plays a definite and strong role in the susceptibility to IDDM, but simple genetic models (dominant, recessive, and intermediate) have been made unlikely on the basis of HLA results; the hypothesis that there are two different susceptibility genes within the HLA system still remains viable, but the demonstration of clinical heterogeneity and/or (better) of different pathogenetic pathways for DR3- and DR4-associated IDDM is required to substantiate it.
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PMID:HLA and disease 1982--a survey. 633 68

Patients with ankylosing spondylitis, psoriatic arthritis, and psoriasis alone were typed for HLA A, B, Cw, and DR antigens, and the antigen frequencies were compared with those in a normal control population and in patients with rheumatoid arthritis. Patients with psoriasis had a significantly raised frequency of Cw6. Those with arthritis in addition to their psoriasis also had raised frequencies of B27 and DR7. Patients with ankylosing spondylitis were characterised by the expected high frequency of HLA B27. Again, those with peripheral arthritis had a higher B27 and DR7 frequency than those without. DR3 is associated with the development of erosions in psoriatic arthritis.
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PMID:Histocompatibility antigens in psoriasis, psoriatic arthropathy, and ankylosing spondylitis. 657 72

TNF-like ligand 1A (TL1A), which binds its cognate receptor DR3 and the decoy receptor DcR3, is an identified member of the TNF superfamily. TL1A exerts pleiotropic effects on cell proliferation, activation, and differentiation of immune cells, including helper T cells and regulatory T cells. TL1A and its two receptors expression is increased in both serum and inflamed tissues in autoimmune diseases such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Polymorphisms of the TNFSF15 gene that encodes TL1A are associated with the pathogenesis of irritable bowel syndrome, leprosy, and autoimmune diseases, including IBD, AS, and primary biliary cirrhosis (PBC). In mice, blocking of TL1A-DR3 interaction by either antagonistic antibodies or deletion of the DR3 gene attenuates the severity of multiple autoimmune diseases, whereas sustained TL1A expression on T cells or dendritic cells induces IL-13-dependent small intestinal inflammation. This suggests that modulation of TL1A-DR3 interaction may be a potential therapeutic target in several autoimmune diseases, including IBD, RA, AS, and PBC.
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PMID:The role of TL1A and DR3 in autoimmune and inflammatory diseases. 2445 14

Objectives. Genome wide association studies identified TNFSF member TNF-like protein 1A (TL1A, TNFSF15) as a potential modulator of ankylosing spondylitis (AS). TL1A is the only confirmed TNFSF ligand of death receptor 3 (DR3, TNFRSF25); however, its role in disease pathology is not characterised. We evaluated DR3's role in controlling osteoblast- (OB-) dependent bone formation in vitro and in vivo. Methods. Osteoprogenitor cells and OB were cultured from male DR3-deficient (DR3(ko)) and wild-type (DR3(wt)) DBA/1 mice. DR3 and RANKL expression were tested by flow cytometry. Alkaline phosphatase and mineralization were quantified. Osteopontin, osteoprotegerin, and pro MMP-9 were measured by ELISA. A fluorescent probe (BoneTag) was used to measure in vivo mineralization in 10-month-old mice. Results. DR3 was expressed on osteoprogenitors and OB from DR3(wt) mice. Alkaline phosphatase, osteopontin, and mineral apposition were significantly elevated in DR3(wt) cultures. Levels of RANKL were comparable whilst osteoprotegerin was significantly increased in DR3(wt) cultures. In vivo incorporation of BoneTag was significantly lower in the thoracic vertebrae of 10-month-old DR3(ko) mice. Conclusions. These data identify new roles for DR3 in regulating OB-dependent bone mineral apposition. They potentially begin to explain the atypical pattern of new bone formation observed in the axial skeleton of grouped, aging DBA/1 mice.
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PMID:Death Receptor 3 (TNFRSF25) Increases Mineral Apposition by Osteoblasts and Region Specific New Bone Formation in the Axial Skeleton of Male DBA/1 Mice. 2606 8