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 'spondyloarthritides' (SpA) comprises ankylosing spondylitis (AS), reactive arthritis, arthritis/spondylitis with inflammatory bowel disease, and arthritis/spondylitis with psoriasis. The main links between these diseases are an association with HLA-B27 and a similar clinical picture. Patients normally present with chronic low back pain or asymmetrical arthritis, predominantly of the lower limbs, and an overlap of these symptoms often occurs. AS is regarded as the most severe subtype. Recent attention has focused on earlier diagnosis of AS among patients with chronic low back, and this is becoming more important as effective therapies for early treatment have become available. AS is a disease of young people, normally starting in the third decade of life. The incidence and prevalence rates of AS, and of SpA as a whole, are strongly dependent and are directly correlated to the prevalence of HLA-B27 in a given population. Incidence rates of 0.5-8.2/100 000 population and prevalence rates of 0.2-1.2% have been described for AS, and about double these figures have been reported for SpA.
Best Pract Res Clin Rheumatol 2006 Jun
PMID:Concepts and epidemiology of spondyloarthritis. 1677 73

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.
Best Pract Res Clin Rheumatol 2006 Jun
PMID:Ankylosing spondylitis and bowel disease. 1677 76

The introduction of symptomatically highly effective anti-tumour necrosis factor alpha therapies for ankylosing spondylitis (AS) has generated interest in the use of imaging to evaluate the potential structure-modifying properties of these agents. Several approaches have been developed to score the plain radiographic abnormalities in AS. Of these, the modified Stoke AS Spinal Score is the most responsive to change, although responsiveness is limited and requires a minimum of 2 years before significant change becomes apparent in patients on standard therapies. Magnetic resonance imaging (MRI) is the most sensitive imaging abnormality, and the advent of fat-suppression imaging allows detection of bone marrow inflammation in the sacroiliac joints as one of the earliest abnormalities in AS. Limited studies have shown that spinal inflammation can be scored reliably using either a system that evaluates the entire spine or a system that limits evaluation to only the most severely affected spinal segments. Both methods also demonstrate excellent responsiveness. The prognostic significance of acute changes on MRI remains unclear. Reliable approaches to the evaluation of chronic changes are yet to be developed. MRI represents a major advance in the diagnostic evaluation of AS.
Best Pract Res Clin Rheumatol 2006 Jun
PMID:Imaging in ankylosing spondylitis. 1677 79

Assessment of disease status and response to therapy in ankylosing spondylitis is a rapidly expanding area of research. The assessment in ankylosing spondylitis international working group has contributed greatly to this development, defining core sets of health domains for use in daily practice and in clinical trials, developing and validating measurement instruments corresponding to these health domains, and developing response and remission criteria for use in clinical trials. This chapter reviews available measures of three major areas of disease impact in ankylosing spondylitis (disease activity, structural damage and functioning), and discusses which measures are relevant for use in clinical practice.
Best Pract Res Clin Rheumatol 2006 Jun
PMID:Assessments in ankylosing spondylitis. 1677 80

The main objectives of medical therapy in ankylosing spondylitis (AS) are to relieve pain, stiffness and fatigue and to prevent structural damage. The Assessment in Ankylosing Spondylitis Working Group has proposed different domains with specific instruments to assess the efficacy of therapeutic agents classified as symptom-modifying and disease-controlling antirheumatic drugs. Non-steroidal antiinflammatory drugs (NSAIDs) are still the first-line treatment in the management of AS, and they are effective in controlling symptoms such as pain and stiffness and maintaining mobility in many patients. A recent randomized trial suggested that the progression of radiological damage occurs less on continuous use of celecoxib compared with on-demand use. If such findings were confirmed by other studies, the therapeutic value of NSAIDs in AS may extend beyond symptom control. However, for each individual patient, the expected advantages of treatment with NSAIDs should be weighted against any possible gastrointestinal and cardiovascular disadvantages. Disease-modifying antirheumatic drugs (DMARDs) are widely used for second-line therapy in AS, but the evidence for their efficacy is poor. The term 'DMARD' has been borrowed from rheumatoid arthritis, and none of the DMARDs have been shown to prevent or significantly decrease the rate of progression of structural damage which is required to be qualified as a disease-controlling antirheumatic drug for AS. Sulphasalazine is the most extensively studied DMARD and studies suggest some degree of clinical benefit confined to peripheral joint involvement, but no evidence of benefit in axial disease. Methotrexate, which is the gold standard DMARD in rheumatoid arthritis, does not seem to have a substantial therapeutic effect in AS on axial or peripheral joint involvement. Leflunomide appears to exert little beneficial effect, if any, even on peripheral joint involvement. There is also good evidence that local therapy with corticosteroids is effective and may be used in selected patients. Oral corticosteroids may be somewhat effective in relieving the symptoms of AS, but this has not been formally studied. Small studies have reported favourable results with intravenous methylprednisolone pulse therapy, but the effect is temporary. Pamidronate and thalidomide have been used in some preliminary trials but need further studies to assess their potential role in treating AS patients resistant or intolerant to other forms of treatment. Treatment with tumour necrosis factor blockers is not discussed in this review.
Best Pract Res Clin Rheumatol 2006 Jun
PMID:Ankylosing spondylitis and symptom-modifying vs disease-modifying therapy. 1677 81

More than three decades after the discovery of HLA-B27 as a major genetic clue to the origins of ankylosing spondylitis, much has been learned about pathogenesis. However, the role of this major histocompatibility complex class I allele remains undefined. Studies from animal models have demonstrated that HLA-B27 overexpression can cause inflammatory disease with spondyloarthritis features, and together with investigations of patient-derived material, both innate adaptive and immune responses have been implicated. The gastrointestinal immune response to pathogens and even normal flora, with subclinical or overt inflammation, may play a role as an environmental component of these diseases. Although there has been a large conceptual emphasis on mechanisms involving autoreactive T-cell recognition of HLA-B27 complexes displaying arthritogenic peptides, and more recently non-canonical recognition of abnormal forms of HLA-B27 free of beta(2)m (heavy-chain dimers or monomers), it remains unclear whether immunological recognition plays a role in pathogenesis. The recognition that the HLA-B27 heavy chain misfolds during assembly, and causes endoplasmic reticulum 'stress', has led to the observation that this activates the unfolded protein response. This has opened additional areas of investigation into the response of immune system cells to protein misfolding, and suggested novel alternative concepts that may explain the role of HLA-B27 in pathogenesis. This chapter will discuss available data and current concepts regarding the pathogenesis of ankylosing spondylitis.
Best Pract Res Clin Rheumatol 2006 Jun
PMID:Pathogenesis of ankylosing spondylitis: current concepts. 1677 83

The association of HLA-B27 with ankylosing spondylitis accounts for nearly 40% of the total disease risk. However, fewer than 5% of B27-positive individuals in the general population become affected. Genomewide scans suggest that other major histocompatibility complex genes further heighten this risk, although linkage disequilibrium with HLA-B27 has confounded their precise identification. Over 31 variants of HLA-B27 have been identified to date, which have evolved from the original B27 allele (B*2705) along three geographic lines. HLA-B*2705 and B*2702 are the primary subtypes in Caucasians with spondylitis, and B*2704 and B*2707 are the primary subtypes in Asians. HLA-B*2706 and B*2709 are not disease associated. There are four theories of how HLA-27 causes spondyloarthritis: (1) HLA-B27 presents a bacterially derived 'arthritogenic peptide' (not yet identified); (2) misfolding or homodimerization of HLA-B27 heavy chains results in a pro-inflammatory response; (3) HLA-B27-positive individuals have deficient intracellular killing of arthritogenic organisms; and (4) HLA-B27 itself, due to sequence homology with bacterial proteins, becomes autoantigenic.
Best Pract Res Clin Rheumatol 2006 Jun
PMID:Major histocompatibility genes and ankylosing spondylitis. 1677 85

There is strong evidence from twin and family studies indicating that a substantial proportion of the heritability of susceptibility to ankylosing spondylitis (AS) and its clinical manifestations is encoded by non-major-histocompatibility-complex genes. Efforts to identify these genes have included genomewide linkage studies and candidate gene association studies. One region, the interleukin (IL)-1 gene complex on chromosome 2, has been repeatedly associated with AS in both Caucasians and Asians. It is likely that more than one gene in this complex is involved in AS, with the strongest evidence to date implicating IL-1A. Identifying the genes underlying other linkage regions has been difficult due to the lack of obvious candidates and the low power of most studies to date to identify genes of the small to moderate magnitude that are likely to be involved. The field is moving towards genomewide association analysis, involving much larger datasets of unrelated cases and controls. Early successes using this approach in other diseases indicates that it is likely to identify genes in common diseases like AS, but there remains the risk that the common-variant, common-disease hypothesis will not hold true in AS. Nonetheless, it is appropriate for the field to be cautiously optimistic that the next few years will bring great advances in our understanding of the genetics of this condition.
Best Pract Res Clin Rheumatol 2006 Jun
PMID:Non-major-histocompatibility-complex genetics of ankylosing spondylitis. 1677 86

Worldwide, over 400,000 patients have been treated with tumour necrosis factor (TNF)-alpha antagonists for indications that include rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis and ankylosing spondylitis. Since their approval, concerns regarding safety have been raised. There is a risk of re-activation of granulomatous diseases, especially tuberculosis, and measures should be taken for detection and treatment of latent tuberculosis infections. Preliminary data suggest that anti-TNF therapy may be safe in chronic hepatitis C. However, TNF-alpha antagonists have resulted in re-activation of chronic hepatitis B if not given concurrently with antiviral therapy. Solid tumours do not appear to be increased with anti-TNF therapy. Variable rates of increased lymphoma risk have been described with anti-TNF therapy compared with the general population, although no increased risk was found compared with a rheumatoid arthritis population. Large phase II and III trials with TNF-alpha antagonists in advanced heart failure have shown trends towards a worse prognosis, and should therefore be avoided in this population. Both etanercept and infliximab are associated with the formation of autoantibodies, and these autoantibodies are rarely associated with any specific clinical syndrome. Rare cases of aplastic anaemia, pancytopenia, vasculitis and demyelination have been described with anti-TNF therapy. This chapter will discuss the safety profile and adverse events of the three commercially available TNF-alpha antagonists: etanercept, infliximab and adalimumab. The data presented in this review have been collected from published data, individual case reports or series, package inserts, the Food and Drug Administration postmarketing adverse events surveillance system, and abstracts from the American College of Rheumatology and European Congress of Rheumatology meetings for 2005.
Best Pract Res Clin Rheumatol 2006 Aug
PMID:Problems encountered during anti-tumour necrosis factor therapy. 1697 37

Tumour necrosis factor alpha (TNF-alpha) plays a crucial role in host defence against bacterial infections. Summarizing the results, the findings of immunological and clinical research suggest a higher infection risk in rheumatoid arthritis and ankylosing spondylitis patients receiving anti-TNF treatment. This is especially true for granulomatous infections in patients treated with the monoclonal TNF-alpha antibodies infliximab or adalimumab. Furthermore, patients treated with TNF inhibitors have a higher susceptibility to infections because of their higher active and more severe disease. Therefore, patients receiving anti-TNF treatment should be closely monitored for serious infections. A rapid and sufficient treatment of infections that are not mild and transient is recommended. There are atypical signs and symptoms as well as atypical pathogen that should be considered. Patients should be educated about how to avoid infectious complications.
Best Pract Res Clin Rheumatol 2006 Dec
PMID:Infection and musculoskeletal conditions: Bacterial and opportunistic infections during anti-TNF therapy. 1712 3


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