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 term seronegative spondylarthropathies is used for an entity of rheumatic syndromes of peripheral joints and the spine (ankylosing spondylitis, reactive arthritis, Reiter's syndrome, arthritis in psoriasis and in inflammatory bowel disease) which are strongly associated with the MHC class I molecule HLA-B27. However, the mechanisms whereby HLA-B27 confers disease susceptibility have so far remained unknown. There is strong evidence that gut inflammation and infection with gram-negative bacteria play a role in the induction of B27-associated disease. HLA-B27, like other MHC class I molecules, physiologically binds antigenic peptides in its binding groove and presents them to CD8+ T lymphocytes. Consequently, if the disease association with HLA-B27 arises from its role as a T-cell restriction element, synovial fluid CD8+ rather than CD4+ T cells should play a prominent pathogenetic role and should be detectable within the affected joints. In this paper, recent studies on bacteria-specific cytotoxic T cells and on peptide binding to HLA-B27 are reviewed. Particular emphasis is laid on the role of HLA-B27 restricted synovial CD8+ T cells with specificity for bacterial antigens or autoantigens. These cytotoxic T cells could provide a missing link in the pathogenesis of the spondylarthropathies and could now serve as tools to identify the critical antigenic epitopes of bacterial and self peptides which are involved in disease induction.
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PMID:Bacteria-specific cytotoxic CD8+ T cells: a missing link in the pathogenesis of the HLA-B27-associated spondylarthropathies. 753 15

During the past year, concepts of spondyloarthropathy and associated gut abnormalities have been further confirmed. In addition, the evolution of spondyloarthropathy to ankylosing spondylitis seems to be determined by the underlying gut inflammation. Other factors present early in spondyloarthropathy that affect the long-term prognosis of the disease have been determined. HLA-B27 has an impact on the severity of spondyloarthropathy. Its presence is also highly associated with uveitis. Paradoxically, HLA-B27+ uveitis is usually benign, with a good prognosis. A subgroup of patients can, however, have severe posterior uveitis; immunosuppressive drugs have been used to treat this disorder.
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PMID:Enteropathic arthritis, Whipple's disease, juvenile spondyloarthropathy, uveitis, and SAPHO syndrome. 754 5

Enteropathic arthritides, uveitis, and Whipple's disease all belong to the category of spondyloarthropathies. The exact mechanism of relationships among joint, tendon, and axial involvement in the spondyloarthropathies, and gut and eye involvement, is unsolved. Different hypotheses have been proposed to explain the role of enterogenic bacteria in interfering with the HLA system and causing inflammatory reactions in these organs. The microorganism responsible for Whipple's disease (Tropheryma whippelii) has been identified by sequencing the largest part of a bacterial 16S ribosomal RNA, followed by polymerase chain reaction amplification. Late-onset pauciarticular juvenile chronic arthritis should be included in the category of the spondyloarthropathies. New cases of ankylosing spondylitis associated with diffuse idiopathic skeletal hyperostosis have been reported.
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PMID:Enteropathic arthritis, uveitis, Whipple's disease, and miscellaneous spondyloarthropathies. 768 29

Gastrointestinal inflammation or infection can be associated with various forms of arthritis, such as, acute reactive arthritis triggered by enteritis due to gram-negative bacteria or ankylosing spondylitis and peripheral arthritis in relation to Crohn's disease and ulcerative colitis. Using colonoscopy, we have found a high prevalence of clinically silent inflammatory lesions in 38 patients (24 males and 14 females) affected by undifferentiated spondyloarthropathies (SpA). Microscopic inflammatory lesions were present in all the patients. Three patterns of nonspecific chronic inflammatory alterations were observed. No difference was noted between patients taking or not taking nonsteroidal anti-inflammatory drugs. Direct immunofluorescence demonstrated the presence of IgG, IgA, IgM, C3, C4 and fibrinogen in 75% of the specimens examined. The finding of chronic inflammatory gut lesions hypothesizes that a local activation of the immune system depending on the persistence of intestinal microbial antigens or toxins, due to impaired elimination or increased exposition, may have a part in the pathogenesis of SpA.
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PMID:Clinically silent inflammatory gut lesions in undifferentiated spondyloarthropathies. 769 56

IgM, IgG and IgA class serum antibodies against the whole Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis bacteria, as well as against K. pneumoniae and E. coli lipopolysaccharides (LPSs) were studied earlier in the sera of 98 patients with ankylosing spondylitis (AS) and in 102 healthy blood donors by enzyme immunoassay. In this study the patients were divided into groups according to the clinical picture, i.e. presence or absence of iritis and enthesitis. The previous major finding of increased IgA class antibody levels against the whole K. pneumoniae bacteria in AS patients when compared to the healthy controls was not specifically associated with any single patient group in the present study. However, the patients with iritis had higher levels of IgA class antibodies to LPS of K. pneumoniae and E. coli when compared to the patients without iritis. In addition, the patients without enthesitis had higher level of IgG class antibodies against whole K. pneumoniae bacteria compared to the patients with enthesitis. The increased IgA class antibody levels against K. pneumoniae and E. coli LPS in AS patients with iritis may reflect an inflammatory process in the gut area. Furthermore, there were certain other differences in the immunological parameters between the AS patients with and without iritis or enthesitis and the possibility that they reflect different mechanisms involved in the disease processes cannot be excluded.
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PMID:Antibodies to Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis in the sera of ankylosing spondylitis patients with/without iritis and enthesitis. 778 69

IgA antibodies against Klebsiella pneumoniae were measured by immunofluorescence in 84 Catalan patients with ankylosing spondylitis (AS), 41 patients with non-inflammatory arthropathies (NIA) and 22 patients with rheumatoid arthritis (RA). Patients with AS showed higher levels of anti-klebsiella IgA antibodies (IgA-Kp) than NIA and RA patients (4.7 +/- 1.6 U vs 3.7 +/- 1.5 U and 3.1 +/- 1.4 U respectively, p = 0.001). In AS patients a significant correlation between IgA-Kp and levels of C-reactive protein was observed. Although no clear correlation was found between IgA anti-klebsiella and total serum IgA levels, a significant correlation between IgA anti-klebsiella and serum levels of secretory IgA was detected (r: 0.43, p = 0.003). In conclusion, some patients with AS disclosed raised levels of Klebsiella antibodies in sera and this is related to an increase of secretory IgA level. Analysis about the relationship between response to klebsiella and the presence of gut inflammation in AS patients could be of interest.
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PMID:Serum IgA anti-Klebsiella antibodies in ankylosing spondylitis patients from Catalonia. 801 81

In ankylosing spondylitis and reactive arthritis, an interplay of microbe and major histocompatibility complex initiates a sequence of events resulting in chronic inflammation. With the use of molecular probes as direct evidence and immune response patterns as indirect evidence, a strong case has been made for a central role of local microbial antigen in reactive arthritis. Cofactors such as gender, persistent gut inflammation, and antibiotic treatment may contribute to this process. Studies of transgenic rats and of familial spondylitis implicate B27 itself as the critical host variable. The results of recent studies point to intimate B27-bacteria interrelationships. HLA-B27 and proteins from enteric bacteria are structurally related, in a manner that may affect T cell response to enteric pathogens. B27 also may directly affect host-microbe interactions by modulating the invasive potential of these bacteria into target cells. Studies are in progress to apply the predictions of these in vitro systems to the in vivo situations of these diseases. The insights of research in the spondyloarthropathies may find broad applications in the rheumatic diseases.
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PMID:Etiopathogenesis of ankylosing spondylitis and reactive arthritis. 806 7

Ileocolonoscopy with biopsy of the colon and terminal ileum was performed prospectively on 12 patients under age 16 with late onset juvenile chronic arthritis (JCA). Inflammatory gut lesions were seen in 9 of these 12 patients; 4 were of the acute type, 5 of the chronic type. Chronic gut inflammation was related to axial inflammatory complaints, inflammatory serum variables, thrombocytosis and sacroiliac radiological abnormalities. A 2nd ileocolonoscopy was performed on 5 of the 12 patients, and a 3rd ileocolonoscopy on 2 of these with persistent synovitis. Gut inflammation and joint inflammation were related; moreover, all 5 patients had chronic inflammatory lesions by the time of the last investigation, one presented with Crohn's disease. The 12 patients were reviewed 3 to 9 years after the first ileocolonoscopy. Four patients were in remission, including the 3 patients with initial normal gut histology. Five patients had developed ankylosing spondylitis (AS), a 6th patient possible AS. Axial inflammatory complaints, a family history of spondyloarthropathies, HLA-B27 positivity, early sacroiliac and peripheral joints radiographic changes, persistence of inflammatory serum variables, thrombocytosis and chronic inflammatory lesions on gut biopsy, are predictive factors in juveniles for evolution to AS. Late onset pauciarticular JCA represents a form of spondyloarthropathy similar to adolescent forms. Persistent gut inflammation could play a role in the pathogenesis of the disease and persistent synovitis.
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PMID:Gut inflammation in children with late onset pauciarticular juvenile chronic arthritis and evolution to adult spondyloarthropathy--a prospective study. 816 17

Ileocolonoscopy was performed on 357 patients meeting the European Spondylarthropathy Study Group criteria for spondyloarthropathy. HLA loci A, B and C were determined in all patients; HLA-B27 was detected in 196 and was absent in the 161 remaining patients. A number of clinical, laboratory and radiological variables were determined before ileocolonoscopy and compared between the HLA-B27+ and HLA-B27- patients. The HLA-B27+ patients were mainly men, with significantly more family members with spondyloarthropathies. Clinical evidence of tendinitis and uveitis was more frequently found in these patients. Like several authors, we found that these patients were more severely affected since they presented more severe radiological involvement of the sacroiliac joints. Syndesmophytes, bamboo spine and erosive joint lesions were more frequent in this group, the hip involvement being of the concentric type. In HLA-B27+ patients ankylosing spondylitis was more prevalent, while in the B27- patients enterogenic, urogenital or undifferentiated spondyloarthropathy was diagnosed. The HLA-B27- patients experienced more episodes of diarrhea, and Crohn-like inflammatory gut lesions were more frequently seen on ileocolonoscopy. In this group a number of patients probably had a form of subclinical Crohn's disease of which the locomotor symptoms were the only clinical expression.
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PMID:A prospective study of patients with spondyloarthropathy with special reference to HLA-B27 and to gut histology. 823 18

Gut inflammation plays a crucial role in the pathogenesis of spondylarthropathies (SpA) since ileocolonoscopic studies have demonstrated the presence of gut inflammation in different forms of this concept: in ankylosing spondylitis (AS) (60%), in enterogenic (90%) and urogenital reactive arthritis (20%), in undifferentiated SpA (65%), in the pauciarticular and axial forms of psoriatic arthritis (16%), in late onset pauciarticular juvenile chronic arthritis (80%) and in acute anterior uveitis (66%). The strong relationship between gut and joint inflammation was demonstrated by performing a second ileocolonoscopy: remission of the joint inflammation was always connected with a disappearance of gut inflammation, whereas persistence of locomotor inflammation was mostly associated with the persistence of gut inflammation. During further evolution 20% of the non-ankylosing spondylitis SpA patients can develop AS. About 6% of the total group SpA patients, in whom inflammatory bowel disease (IBD) was excluded, developed Crohn's disease 5 to 9 years later. All these patients initially presented with gut inflammation, which indicates that this finding has prognostic value. The high prevalence of evolution to IBD in SpA patients confirms the thesis that both disease entities bear common pathogenic mechanisms, and confirms the place of IBD in the concept of SPA. Sulphasalazine (SASP), a successful drug in the treatment of IBD, has demonstrated its effectiveness in the treatment of SpA. The beneficial effect of the drug in this disease entity could be due to its anti-inflammatory effect on the gut wall, by normalizing its permeability and by preventing the entrance of antigens through the defective gut wall. However, SASP could not prevent the evolution to IBD.
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PMID:Course of gut inflammation in spondylarthropathies and therapeutic consequences. 867 45


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