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)

Approximately one third of all patients with Crohn's disease and ulcerative colitis suffer from extra-intestinal manifestations of their inflammatory bowel disease. Most commonly those symptoms occur simultaneously with the CED symptoms; they can, however, either precede them or appear later on in the course of the disease. The most frequent extra-intestinal symptoms are arthralgias of peripheral joints and spine, which are usually bland and self-limiting, while ankylosing spondylitis and erosive arthritides are rare. Skin lesion and eye affections can also parallel the bowel condition, but occasionally they precede intestinal manifestations and can be a first diagnostic clue. In addition, different extra-intestinal symptoms tend to simultaneously co-occur more frequently in some patients with CED, while others are not affected at all. Immunogenetic parameters play a role for the manifestations of the pathologic immune response both in the gut and in the musculo-skeletal systems, as indicated by associations with MHC class I alleles. Enteropathic microorganisms are also thought to be involved in the pathogenetic mechanisms.
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PMID:[Extra-intestinal Manifestations of chronic inflammatory Bowel diseases]. 1193 Mar

Spondyloarthropathies are a cluster of interrelated and overlapping chronic inflammatory rheumatic diseases that primarily include ankylosing spondylitis, reactive arthritis, and the arthritis associated with psoriasis and inflammatory bowel diseases. The primary pathologic sites are the entheses (the sites of bony insertion of ligaments and tendons); the axial skeleton, including the sacroiliac joints; the limb joints; and some nonarticular structures, such as the gut, skin, eye, and aortic valve. Although spondyloarthropathies are not associated with rheumatoid factor, they show a strong association with HLA-B27; however, this association varies markedly among various spondyloarthropathies and among ethnic groups. The most widely used classification criterion, from the European Spondyloarthropathy Study Group, encompasses the currently recognized wider disease spectrum, with a sensitivity and specificity that generally exceed 85%. Spondyloarthropathies occur in genetically predisposed persons and are triggered by environmental factors, but the cellular and molecular mechanisms of inflammation are not yet fully understood. Chlamydial and many enterobacterial infections can trigger reactive arthritis, but an infectious trigger for ankylosing spondylitis has not yet been established. HLA-B27 itself is involved in enhancing genetic susceptibility, but the underlying molecular basis is still unknown; additional genes include the putative susceptibility genes for Crohn disease, ulcerative colitis, and psoriasis. A specific susceptibility gene for Crohn disease, NOD2, is located on chromosome 16q12, and one of the candidate genes for psoriasis, PSORS1, has been mapped to a 60-kb fragment on chromosome 6p, which is telomeric to the HLA-C locus. This paper reviews the efficacy of anti-tumor necrosis factor-alpha therapy and other therapeutic advances.
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PMID:Update on spondyloarthropathies. 1206 64

Clinical studies indicate an important role for bowel inflammation in ankylosing spondylitis and other spondyloarthropathies whereby two different aspects have to be considered. First, the gut inflammation is clinically and histologically closely related to Crohn's disease. Recent data on subclinical immune alterations confirm this relationship and suggest that spondyloarthropathy is a unique human model for studying early Crohn's disease. Second, bowel and peripheral joint inflammation are clinically, histologically and pathogenetically linked. The most important clinical implication of these observations is that targeted therapies for Crohn's disease could also be effective for intestinal as well as extra-intestinal disease manifestations in spondyloarthropathy, as evidenced by the recent studies on TNF-alpha blockade. Unravelling the gut-synovium axis in spondyloarthopathy could also contribute to the identification of new therapeutic targets. Finally, assessment of subclinical gut inflammation by histology, serology and genetics could contribute to the stratification of individual patients in subgroups with an optimal response to specific therapeutic interventions.
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PMID:Ankylosing spondylitis and bowel disease. 1240 26

Spondyloarthropathies (SpA) are a group of related disorders with common clinical and genetic characteristics. The prototype disease in this group is ankylosing spondylitis; other entities include reactive arthritis, psoriatic arthritis, and arthritis in patients with inflammatory bowel disease. Over recent years, there has been a special interest in the relation between spondylitis/synovitis and gut inflammation in patients with SpA. Two thirds of patients with undifferentiated SpA show histologic signs of gut inflammation, and a fraction of these patients go on to develop clinically overt Crohn's disease. In this review, the authors will focus on 1) the growing evidence that has been provided that gut inflammation in SpA is immunologically related to Crohn's disease, based on the molecular characterization of the inflammation (lymphocyte homing markers and ligands, T cell cytokines, macrophage markers, and serology); and 2) on the therapeutic implications resulting from this concept. The recent introduction and positioning of anti-tumor necrosis factor-alpha therapy in patients with ankylosing spondylitis and other types of SpA is, in large part, based on this concept.
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PMID:Gut inflammation and spondyloarthropathies. 1242 69

Peripheral involvement of the joints, including pauciarticular, asymmetrical, transitory and migrating synovitis and enthesiopathy, is observed in 10-20% of affected inflammatory bowel disease patients. Recurrence is common and frequently coincides with a flare-up of intestinal disease. The true prevalence of axial involvement is less well established. Sacroiliitis is a hallmark of spondylitis, but is under-reported due to its insidious onset and sometimes asymptomatic nature. Radiographic evidence of sacroiliitis is present in about 20-25% of patients. Ankylosing spondylitis, as defined by the Rome criteria, is present in 3-10% of inflammatory bowel disease patients, and is thought to have a different genetic predisposition in these patients compared with 'classic' ankylosing spondylitis: whereas the human leucocyte antigen B27 phenotype is present in 90% of patients with 'classic' ankylosing spondylitis, the prevalence decreases to only 30% in patients with ankylosing spondylitis secondary to Crohn's disease. Polymorphisms involving CARD15 appear to be a possible genetic trigger: 78% of patients with Crohn's disease and symptomatic or asymptomatic sacroiliitis carry at least one mutation, compared with only 48% of control Crohn's disease patients. Moreover, in other forms of spondyloarthropathy, a similar association has been reported: 42% of patients with spondyloarthropathy and associated asymptomatic chronic gut inflammation, who are considered likely to develop Crohn's disease and ankylosing spondylitis, are carriers of at least one CARD15 mutation, compared with only 7% of patients with normal histology. In addition to genetic markers, clinical features support the relationship between gut and joint pathophysiology. In cases of spondyloarthropathy, a very rapid, substantial and sustained improvement in symptoms has been reported following treatment with infliximab, suggesting an essential role for tumour necrosis factor-alpha in spondyloarthropathy, similar to that observed in Crohn's disease.
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PMID:Review article: joint involvement in inflammatory bowel disease. 1535 92

A great deal of progress has occurred in the past few years in elucidating the causes and designing new treatments for ankylosing spondylitis and other types of spondyloarthritis. In addition to the human leukocyte antigen (HLA)-B27 and other major histocompatibility complex (MHC) genes, chromosomal regions and genes elsewhere in the genome are being implicated both in disease susceptibility and severity. The various ways HLA-B27 may function in causing spondyloarthritis now are better understood to encompass not only antigen presentation but also other mechanisms, possibly all being operative in pathogenesis (misfolding of the HLA-B27 molecule, impaired intracellular killing of bacteria, and HLA-B27 itself serving as an autoantigen). Specific enteric and sexually acquired infections can trigger reactive arthritis, though no specific microbe has been identified in other forms of spondyloarthritis. Intestinal inflammation with impairment of the gut:blood barrier may be operative in driving ankylosing spondylitis and enteropathic arthritis. A number of treatments have been tried in spondyloarthritis, including older agents such as methotrexate and sulfasalazine but also newer drugs such as pamindronate. The recent introduction of tumor necrosis factor (TNF) blockers in the treatment of spondyloarthritis has offered the most hope in not only relieving symptoms and signs of both peripheral arthritis and enthesitis but also spinal disease, which often has been refractory to other agents. Their high cost and considerable side effect profile, however, have necessitated the establishment of guidelines for their use in these diseases in order to target the patient in whom they are likely to have the most benefit.
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PMID:Spondyloarthritis: update on pathogenesis and management. 1592 88

Between 5 and 10% of cases of ankylosing spondylitis (AS) are associated with inflammatory bowel disease (IBD), either Crohn's disease or ulcerative colitis. A much larger percentage of AS patients have subclinical gut inflammation manifested either by endoscopic findings or by histology. The association with HLA-B27 is less strong in IBD-associated AS than in idiopathic AS, and there is evidence for an association between gut inflammation in AS with the Crohn's-disease-related CARD15 mutations. Despite the different genetics, the immunopathology suggests common inflammatory pathways in gut and joint inflammation in AS, and in gut inflammation in AS and IBD. Although this observation is of interest to unravel the pathophysiology of the disease, systematic screening of AS patients by ileocolonoscopy is not indicated in the absence of gut symptomatology as only a small proportion of AS patients with subclinical gut inflammation will develop overt IBD over time. Treatment of AS associated with IBD with non-steroidal anti-inflammatory drugs (NSAIDs) is problematic because of concerns of potential re-activation of IBD by NSAIDs. Major advances have been made in recent years with the establishment of anti-tumour necrosis factor (TNF) therapy in AS, the other spondyloarthritides and IBD. Anti-TNF agents are of particular relevance to AS patients with concomitant IBD who are at risk of exacerbation of the underlying bowel disease when treated with NSAIDs. In IBD, infliximab, unlike etanercept, is effective in treating clinical symptoms, inducing and maintaining remission, and mucosal healing. Adalimumab appears to be effective in treating both AS and IBD; however, official approval is pending. Currently, infliximab is the drug of choice for the treatment of patients with active AS associated with IBD.
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PMID:Ankylosing spondylitis and bowel disease. 1677 76

The nucleotide-binding domain, leucine-rich repeat containing family (NLR) network has provided pivotal genetic and molecular insights into diseases that were hitherto regarded as autoimmune. The NLR-related disorders include rare monogenic autoinflammatory diseases collectively termed cryopyrin-associated periodic syndromes, Crohn's disease which is a common polygenic disease and also an association at the mechanistic level with gout and pseudogout. Unlike the classical autoimmune diseases where disease immunopathogenesis is played out primarily in the primary and secondary lymphoid organs, the immunopathogenesis of the NLR-related disorders is played out in the tissues where inflammation arises. As the genetic mutations or molecular cascades associated with the NLR-related disorders have a widespread cellular distribution, it has been somewhat enigmatic why these disorders attack certain territories, but not others. This implies that tissue-specific factors in the target organs themselves contribute to disease expression. Such examples include the high abundance of NOD2 expressing cells in the part of the gut most typically afflicted by Crohn's disease and the preferential deposition of crystals in the joints to where inflammation localises in gout and pseudogout. The NLR network is associated principally with increases in TNF or IL-1 production, both of which are key players in innate immunity. Therefore, the NLR network identifies at the genetic and molecular level a robust paradigm for innate immune activation against self. This tissue-specific-factor-associated inflammation is the diametric opposite of classical autoimmunity. Of note, the MHC class-I-associated diseases including psoriasis (HLA-Cw6) and ankylosing spondylitis (HLA-B27) show striking clinical overlaps with Crohn's disease and also some rare monogenic diseases. Thus, the NLR innate immune pathway allows the full spectrum of inflammation against self to be viewed along an immunological disease continuum with autoantibody-associated disease at one end, innate immune diseases at the other and MHC class-1-related disorders as an intermediate.
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PMID:The NLR network and the immunological disease continuum of adaptive and innate immune-mediated inflammation against self. 1780 42

The aim of this cross-sectional study was to evaluate the frequency of intestinal inflammation and its association with disease activity, functional status and quality of life in patients with ankylosing spondylitis (AS). A total of 25 patients with AS had undergone ileocolonoscopy and concomitant histological study. Clinical and demographical parameters, BASDAI, BASFI, and SF-36 scores were compared between patients with and without macroscopic gut inflammation (MGI). Colonoscopic study revealed MGI in 9 patients and macroscopically normal gut mucosa in 16 patients. On histological examination, of 25 patients 20 had gut inflammation, mostly in ileum. BASDAI score was higher (P < 0.05), SF-36 pain and physical scores, and chest expansion measurement were lower (P = 0.00, P = 0.01, P = 0.01), duration of morning stiffness was longer (P = 0.01) in patients with MGI. Serum C-reactive protein, erytrocyte sedimentation rate levels were similar between groups (P > 0.05). There is high prevalence of histological gut inflammation in AS patients. More active disease should suggest gut inflammation in AS patients.
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PMID:Association of macroscopic gut inflammation with disease activity, functional status and quality of life in ankylosing spondylitis. 1903 Aug 65

Subclinical gut inflammation has been described in up to two-thirds of patients with spondyloarthropathies (SpA). Arthritis represents an extra-intestinal manifestation of several gastrointestinal diseases, including inflammatory bowel disease (IBD), Whipple's disease, Behcet's disease, celiac disease, intestinal bypass surgery, parasitic infections of the gut and pseudomembranous colitis. Moreover about two-thirds of nonsteroidal anti-inflammatory drug users demonstrate intestinal inflammation. Arthritis may manifest as a peripheral or axial arthritis. The spondyloarthropathy family consists of the following entities: ankylosing spondylitis, undifferentiated spondyloarthritis, reactive arthritis, psoriatic arthritis, spondyloarthritis associated with IBD, juvenile onset spondyloarthritis. This topic reviews the major gastrointestinal manifestations that can occur in patients with SpA and in nonsteroidal anti-inflammatory drugs users.
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PMID:Gastrointestinal lesions associated with spondyloarthropathies. 1946 92


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