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)

In addition to HLA-B27, other genetic factors are thought to be involved in the pathogenesis of ankylosing spondylitis (AS). Because of the localization, in the proximity of the HLA-B locus, and the biological activities of TNF-alpha, we investigated the association between AS and a single base polymorphism located at position -308 of the TNF-alpha gene. An allele-specific polymerase chain reaction was developed to monitor this polymorphism. The frequency of the TNF-alpha alleles was determined in 66 AS patients and 37 healthy controls. The TNF-alpha allele frequency was not significantly different between AS patients and controls.
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PMID:Polymorphism of tumour necrosis factor-alpha (TNF-alpha) at position -308 in relation to ankylosing spondylitis. 803 19

Five different subtypes of spondyloarthropathy (SpA) are now recognized. Clinical and radiologic involvement of the sacroiliac joint is an outstanding feature of the SpA, especially ankylosing spondylitis (AS). In this partly debilitating form of SpA a unique type of inflammatory axial involvement is observed which is characterized by inflammation and new bone formation at different spinal sites. In longstanding disease sacroiliitis, spondylitis and spondylodiscitis are easily recognized by conventional radiography and even better by computed tomography--especially when bony changes have already taken place. The advantage of dynamic magnetic resonance imaging (MRI) is to visualize morphologic changes and inflammation at the same time. This facilitates detection of sacroiliitis and spondylitis/spondylodiscitis at early time points. Hopefully, this will lead to other forms of therapy to prevent ankylosis of the spine. The origin of the granulation tissue infiltrating cartilage and bone in AS might be the synovium, the subchondrium or the bone marrow itself. T cells and macrophages seem to play an important role in this inflammatory process in which TNF-alpha is present in severe cases. The mechanisms responsible for the increased bone formation observed in the course of AS are unknown.
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PMID:Radiologic diagnosis and pathology of the spondyloarthropathies. 989 7

Juvenile rheumatoid arthritis (JRA) and juvenile systemic lupus erythematosus (JSLE) are the most common autoimmune rheumatic diseases in children associated with high levels of autoantibodies and immune reactivity. JRA and JSLE are more common in girls. Disease activity is worse in the morning, improves during the daytime and worsens at night suggesting that neuroendocrine immune mechanisms are involved in disease pathophysiology. Adult patients with RA and SLE have excessive levels of prolactin (PL) while cortisol (CS) production is down-regulated for the degree of ongoing inflammation. PL has potent proinflammatory properties. Normal to low levels of cortisol have been observed in children with active JRA despite the high serum levels of IL-6, IL-1 beta, and TNF-alpha, which activate the hypothalamic-pituitary-adrenal axis (HPA). The CS levels are in fact subnormal because inflammatory stress activates the HPA. Normal serum PL levels were seen in children with JRA, most of whom were not active with higher levels in those with active ANA +ve JRA complicated by uveitis. A trend toward high PL levels was seen in 33 children with JSLE. High serum PL levels are seen in patients with active juvenile ankylosing spondylitis (JAS) only. Growth retardation is a feature of JRA. Patients with JRA have low to normal levels of growth hormone (GH) and low levels of insulin-like growth factor 1 (IGF-1). IGF-1 mediates the effects of GH. The observation of low IGF-1 in JRA raises the therapeutic possibility with IGF-1. Overall, high levels of follicle stimulating hormone and luteinizing hormone are found in children with JSLE while the levels in JRA tend to be normal. Testosterone levels are low in patients with JRA. No significant differences in estrogen levels have been found between patients with JRA and those with JSLE and matched controls. There is evidence that the autonomic nervous function is defective in patients with JRA.
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PMID:Neuroendocrine immune features of pediatric inflammatory rheumatic diseases. 1041 95

Characterization of non-B27 susceptibility genes will be required to know the pathogenesis of AS. The aim of this study was to examine whether ankylosing spondylitis (AS) susceptibility is controlled by B27 alone rather than B27 haplotypes and, whether other closely related class I loci, such as MICA and TNFA genes might play a role in AS. Three hundred eleven B27-positive samples from Caucasoid, Asian, and African populations were selected and genotypes were carried out by PCR/SSOP (HLA-B27 and HLA-C), PCR/SSP (MICA-TM polymorphism in the transmembrane region), PCR/SSCP (MICA alleles), and PCR-RFLP (TNF-alpha). Of these, 161 were AS patients, chosen in order to investigate the contribution of TNFA and MICA loci to AS in HLA-B27 positive individuals. Some findings can be concluded from the study: (a) No significant differences of TNF-alpha promoter alleles at position -308 and -238 (A/G) were found between AS patients and B27 matched alleles from healthy controls; (b) strong linkage disequilibrium was found between the B27 and the MICA alleles. The MICA-A4 was found to be in association with B*2705,02,03 and 08; MICA-A5 with B*2704 and B*2707 and MICA-A.5.1 with B*2706; (c) no significant differences of MICA alleles were found between AS and controls carrying the B27-associated alleles, and therefore no evidence is provided for an additional role of MICA gene in AS susceptibility; (d) there are a striking correlations between the structure of B27 extended haplotypes (from MICA region to HLA-C) and the ethnic distribution of these subtypes. The results of differential linkage disequilibrium with HLA-B27 subtypes suggest that B27 itself remains the primary gene for AS susceptibility, and TNFA and MICA are not involved in the pathogenesis of the disease.
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PMID:HLA-B27 alone rather than B27-related class I haplotypes contributes to ankylosing spondylitis susceptibility. 1071 5

In patients with established ankylosing spondylitis (AS) and a healthy control group, plasma levels of IGF-1 and TNF-alpha as well as possible connections with biochemical markers of the bone metabolism, humoral inflammatory activity (ESR, CRP), clinical manifestations, and an established clinical activity score (Bath Ankylosing Spondylitis Activity Index = BASDAI) were examined. In AS-patients (men and women) significantly increased TNF-alpha levels were found. Moreover, patients with enthesopathy showed a significantly more frequent increase of CRP and TNF-alpha levels besides an increased urinary pyridinium cross-link excretion. In addition, a significant positive correlation between TNF-alpha, CRP, BASDAI, and urinary pyridinium cross-link excretion was proved, besides a significant negative correlation of IGF-I to urinary pyridinium cross-links and TNF-alpha levels. Summing up, it may be said that TNF-alpha seems to be a reliable surrogate marker in enthesitis. This was proved so far for IgA and endothelium stimulating angiogenic factor only. Besides, the present results argue against a stimulation of osteogenesis. The catabolic situation under high TNF-alpha and low IGF-1 levels may play an important role in the pathogenesis of osteoporosis in AS.
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PMID:Correlation between plasma TNF-alpha, IGF-1, biochemical markers of bone metabolism, markers of inflammation/disease activity, and clinical manifestations in ankylosing spondylitis. 1114 93

Spondyloarthropathies (SpA) are a group of related disorders. The hallmark symptoms include spondylitis, pauci-articular synovitis and enthesiopathy. In an important number of cases, subclinical gut inflammation with pathological findings resembling Crohn's disease can be found. Some of these patients may eventually develop overt Crohn's disease. Conventional medical therapy in patients with SpA consists of non-steroidal anti-inflammatory drugs (NSAIDs). Sulphasalazin can be co-administered, especially in cases of chronic synovitis or enthesiopathy. Recently, experience with anti-TNF-alpha monoclonal antibodies (infliximab), a new class of biological compounds, has opened new avenues for treating patients with SpA. In particular, infliximab used in two open studies gave significant benefit on the locomotor manifestations in patients with Crohn's disease, in patients with ankylosing spondylitis, undifferentiated SpA and psoriatic arthritis. Etanercept, another TNF-alpha antagonist (soluble receptor), was shown to induce benefit in a placebo-controlled study in patients with psoriatic arthritis. The relationship between SpA and inflammatory bowel disease lead to the hypothesis that interfering with gut inflammation in patients with SpA would yield a potential target for modulating the synovitis in these patients. Thus, besides TNF-alpha blockade, other strategies with potential efficacy can be envisioned, such as IL-10, ICAM-1 antisense or anti-(4)beta(7) antibodies.
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PMID:Current use of biologicals for the treatment of spondyloarthropathies. 1133 71

Tumor necrosis factor-alpha is a major effector and regulatory cytokine, which seems to have an outstanding position in rheumatic and other inflammatory states. Because TNF-alpha has been detected in the inflamed gut and sacroiliac joints of patients with chronic inflammatory bowel diseases and spondyloarthritides, like ankylosing spondylitis, there was need for studies of the efficacy of the modern biologic anti-TNF agents infliximab and etanercept in these diseases. Infliximab is approved for the treatment of Crohn disease. In addition, there are now also positive data for infliximab in the treatment of ankylosing spondylitis and for etanercept and infliximab in the treatment of psoriatic arthritis.
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PMID:New treatment options in spondyloarthropathies: increasing evidence for significant efficacy of anti-tumor necrosis factor therapy. 1155 23

Therapeutic options for patients with more severe forms of spondyloarthritis (SpA) have been rather limited in recent decades. There is accumulating evidence that anti-tumor-necrosis-factor (anti-TNF) therapy is highly effective in SpA, especially in ankylosing spondylitis and psoriatic arthritis. The major anti-TNF-alpha agents currently available, infliximab (Remicade(R)) and etanercept (Enbrel(R)), are approved for the treatment of rheumatoid arthritis (RA) in many countries. In ankylosing spondylitis there is an unmet medical need, since there are almost no disease-modifying antirheumatic drugs (DMARDs) available for severely affected patients, especially those with spinal manifestations. Judging from recent data from more than 300 patients with SpA, anti-TNF therapy seems to be even more effective in SpA than in rheumatoid arthritis. However, it remains to be shown whether patients benefit from long-term treatment, whether radiological progression and ankylosis can be stopped and whether long-term biologic therapy is safe.
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PMID:Therapy of ankylosing spondylitis and other spondyloarthritides: established medical treatment, anti-TNF-alpha therapy and other novel approaches. 1222 5

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

The therapeutic options for patients suffering from the more severe forms of spondyloarthritis (SpA) have been rather limited in recent decades. There is now accumulating evidence that anti-tumour necrosis factor (anti-TNF) therapy is highly effective in SpA, especially in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Based on the data recently published on more than 200 AS patients, and more than 100 PsA patients, this treatment seems to be even more effective than it is in rheumatoid arthritis (RA). The two major anti-TNF-alpha agents currently available, infliximab (Remicade) and etanercept (Enbrel), are approved for the treatment of RA in Europe and in the USA. The situation in SpA is different from RA because there is an unmet medical need, especially in AS, because disease-modifying anti-rheumatic therapy is not available for severely affected patients. Thus, TNF blockers might even be considered first-line immunosuppressive treatment in patients with active AS who are not sufficiently treated with non-steroidal anti-inflammatory drugs (NSAIDs). For infliximab, a dose of 5mg/kg was required, and intervals between 6 and 12 weeks were necessary for constant suppression of disease activity - a major aim also for long-term treatment. However, it remains to be shown whether patients benefit from long-term therapy and whether radiological progression and ankylosis can be stopped. The optimal doses of infliximab might well be determined individually. Allergic reactions and increased susceptibility to tuberculosis are rare side-effects which need to be recognized early. As it stands now, the benefits of anti-TNF therapy in AS seem to outweigh these shortcomings. The efficacy of etanercept was first demonstrated in PsA. A double-blind study has now been performed in AS - with similar results. There is preliminary evidence that both agents also work in other SpA such as undifferentiated SpA. Hopefully, both agents will be approved soon for the short-term treatment of severe SpA. In parallel, studies should be performed to document the long-term efficacy and safety of this treatment.
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PMID:Therapy for ankylosing spondylitis: new treatment modalities. 1240 31


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