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)

A component of the cell walls of certain enteric bacteria has been identified that cross-reacts with an HLA-B27-associated cell-surface structure on lymphocytes and other cell types from patients with ankylosing spondylitis. This component, or "modifying factor," from one particular organism, Klebsiella K43-BTS1, has been studied in detail. A purification scheme has been developed using preparative electrofocusing and gel-permeation high performance liquid chromatography techniques and the purified material used in various characterization studies. A previous study demonstrated that the modifying factor has an approximate molecular weight of 30,000 and an isoelectric point of 5.4-5.5. In this study two-dimensional gel electrophoresis experiments demonstrated that the modifying factor is associated with a single protein component of the cell wall of this organism. Pronase and papain destroyed the modifying factor activity whereas trypsin and alpha-chymotrypsin degraded the factor into smaller fragments without destroying its ability to modify B27+ AS- lymphocytes. Neuraminidase did not affect the modifying factor itself but did affect B27+ AS- lymphocytes such that they became unresponsive to modification. Sugar inhibition studies suggested that sugar groups are probably not involved in the function of the modifying factor. The availability of purified modifying factor should permit more detailed chemical analyses as well as functional studies to determine the significance of this molecule to the pathogenesis of ankylosing spondylitis.
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PMID:Biochemical studies on a factor isolated from Klebsiella K43-BTS1 that cross-reacts with cells from HLA-B27 positive patients with ankylosing spondylitis. 353 95

Neutral protease, collagenase and elastase activities were high in synovial fluids from inflammatory arthritic diseases such as gout, active rheumatoid arthritis and ankylosing spondylitis. The activities correlated well with biochemical parameters such as CRP, ESR and total protein. Values were much lower in a non-inflammatory fluid from a patient with osteoarthrosis. Treatment of fluids with trypsin released both collagenase and elastase. The fluids possessed reserve inhibitory action against these enzymes presumably due to plasma antiproteases being present. The collagenase present was found to possess a MW of 32,700 daltons.
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PMID:Neutral protease, collagenase and elastase activities in synovial fluids from arthritic patients. 609 75

It has been shown that HLA-B27 lymphocytes from healthy individuals (B27+ ankylosing spondylitis [AS]-), which are not lysed by an antiserum against Klebsiella K43, can be rendered susceptible to lysis after incubation in the culture filtrate of Klebsiella K43. This finding is compatible with a specific modification by a Klebsiella K43-derived soluble factor of a B27-associated lymphoid cell component. Preliminary characterization of the factor has indicated that it is nondialyzable, but it is heat labile at 56 degrees C for 30 min and has a 35,000-50,000 mol wt. The modifying factor activity of the filtrate is destroyed by neuraminidase but not by trypsin and alpha-chymotrypsin. Furthermore, the ability of the factor to convert B27+AS- lymphocytes can be specifically absorbed by B27+AS- lymphocytes, but not by B27+AS+, B27-AS+, or by B27-AS- lymphocytes, which suggests that B27+AS- cells carry a hypothetical receptor which can specifically bind a Klebsiella K43 antigenic determinant. These results imply that the modification by environmental agents of specific major histocompatibility complex-associated gene products may be an important element in the pathogenesis of the HLA-B27-linked seronegative arthropathies.
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PMID:Characterization of a factor(s) present in Klebsiella culture filtrates that specifically modifies an HLA-B27-associated cell-surface component. 615 68

Moderate titres of antiviral activity were demonstrated in 48-58% of sera obtained from patients suffering from seropositive and seronegative rheumatoid arthritis (RA), psoriatic arthritis, Reiter's syndrome, ankylosing spondylitis, and juvenile rheumatoid arthritis. Sera from blood donors and from patients with various noninflammatory diseases were positive in 16% of cases. The activity was species-specific, mediated by the homologous cells, and destroyed by treatment with trypsin and exposure to pH 2. Antibodies against human IFN-alpha did not neutralise the activity. These characteristics are compatible with those of IFN-gamma or immune interferon. Neither the presence nor the titre of IFN was correlated with disease activity defined by concentration of C-reactive protein, C3 concentration, and erythrocyte sedimentation rate. IFN-gamma was present in 4 of 10 synovial fluids from patients with RA. The titre in one of these was higher than in the corresponding serum, indicating local production in the rheumatoid joint.
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PMID:Immune interferon in serum and synovial fluid in rheumatoid arthritis and related disorders. 641 86

Although the association between human histocompatibility leukocyte antigen (HLA) B27 and ankylosing spondylitis is the prototype of HLA-disease association, the mechanism underlying these associations has not been determined. We have investigated the possibility that the B27 molecules from patients with ankylosing spondylitis are different from those of normals, and only the "different" molecules predispose the individual to disease. Biosynthetically radiolabeled HLA-B27 molecules from patients with ankylosing spondylitis and normal individuals were compared by two-dimensional gel electrophoresis and tryptic peptide mapping with high pressure liquid chromatography. Extensive charge heterogeneity in the 45,000-dalton heavy chain was detected when B27 molecules were analyzed by two-dimensional gel electrophoresis; the charge heterogeneity was reduced, but not eliminated, when the B27 molecules were treated with neuraminidase to remove sialic acid residues before analysis. No structural difference in the B27 molecules from an ankylosing spondylitis patient and a normal individual were detected by two-dimensional gel electrophoresis. Analysis of [(3)H]leucine-labeled and [(3)H]arginine-labeled tryptic peptides and chymotryptic peptides of the trypsin insoluble material by reverse-phase high pressure liquid chromatography revealed identity of the B27 molecules from ankylosing spondylitis patients and normal individuals. These studies indicate that development of akylosing spondylitis in only some B27 positive individuals is not attributable to those individuals possessing variant B27 molecules.
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PMID:Structural identity of human histocompatibility leukocyte antigen-B27 molecules from patients with ankylosing spondylitis and normal individuals. 705 55

Refolding of the heavy chain of the Class I HLA molecule, HLA-B27, in the absence of beta(2)m, yields soluble high molecular weight (HMW) oligomers reminiscent of the oligomeric forms of beta(2)m-free heavy chains (FHCs) of class I HLA antigens observed on cell surfaces. Here we examine the structural characteristics of HMW B27 in respect of features potentially relevant to autoimmunity, such as: (a) retention of native-like structure, since this could facilitate non-canonical interactions with T-cell receptors even in the absence of bound beta(2)m and peptide, or (b) presence of non-native structure, since this could yield novel (non-self) antigenic conformational epitopes that could elicit immune attack. We report that HMW B27 is characterized by high secondary structural content, structural stability, stability to proteolysis by trypsin, and structural features that are both partly native-like, and partly non-native-like, as assessed through the binding of conformationally-distinguishing and cross-reacting scFv antibodies specifically selected against HMW B27. We also present cell ELISA data with conformation-specific scFv antibodies that distinguish between lymphocytes from individuals who are healthy and B27 positive, and those who are B27 positive but suffering from ankylosing spondylitis.
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PMID:Refolding of HLA-B27 heavy chains in the absence of beta2m yields stable high molecular weight (HMW) protein forms displaying native-like as well as non-native-like conformational features: implications for autoimmune disease. 1803 53

Objective To investigate the changes of protein phosphorylation in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and its potential regulatory role in AS. Methods PBMCs were obtained from 20 cases of AS without treatment, 15 cases of AS with drug treatment, and 20 matched healthy controls. Protein extraction, trypsin digestion, phosphorylated peptide enrichment and mass spectrometric analyses were performed. AS-related phosphorylated proteins were screened by bioinformatics analysis, and the changes of expression levels of these proteins after treatment were analyzed. Results A total of 1561 significantly differential phosphorylated peptides were detected, of which 756 peptides from 472 proteins were up-regulated, and 805 from 363 proteins were down-regulated. GO enrichment analysis showed that the proteins with altered phosphorylation were mainly involved in biological processes such as neutrophil activation and platelet aggregation. The enrichment analysis of KEGG pathway showed infection, platelet activation, T cell receptors and B cell receptor signaling pathways might be closely related to AS. Conclusion This study systematically depicted the change of protein phosphorylation in PBMCs of AS patients, providing important information to understand the pathogenesis and disease progression mechanism of AS.
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PMID:[Phosphoproteomic analysis of peripheral blood mononuclear cells of ankylosing spondylitis patients]. 3269 57