Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01889 (ankylosing spondylitis)
 5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the 25 years since the initial reports of the association of HLA-B27 with ankylosing spondylitis (AS) and subsequently with Reiter's syndrome, psoriatic spondylitis, and the spondylitis of inflammatory bowel disease, the association of HLA-B27 with the seronegative spondyloarthropathies has remained one of the best examples of a disease association with a hereditary marker. HLA-B27 has been recognized as representative of a spectrum of diseases, ranging from the majority of HLA-B27-positive individuals who have no disease at all, through those with isolated eye or skin involvement, to those with critical eye, heart, and peripheral joint compromise of full-blown AS. Yet HLA polymorphism has evolved in response to environmental stresses, and even the presence of HLA-B27 itself appears to confer advantages in certain infectious diseases, such as acquired immune deficiency syndrome (AIDS). This article will review what is currently known about HLA-B27 and disease, especially in the seronegative spondyloarthropathies. The structure-function relationship of HLA-B27 will be presented, including differences between the B27 subtypes both in their ethnic variation and possible disease implications. The disease spectrum conferred by the presence of HLA-B27 will also be discussed, and the theories of how HLA-B27 contributes to the pathogenesis of the spondyloarthropathies will be considered.
 ...
PMID:HLA-B27 and the seronegative spondyloarthropathies. 976 85

Eye inflammation, especially uveitis, is a prominent feature of spondyloarthropathies. Uveitis associated with ankylosing spondylitis and Reiter's syndrome usually is a unilateral acute anterior uveitis with a high tendency to recur sometimes in the contralateral eye. Uveitis associated with undifferentiated spondyloarthropathy, inflammatory bowel disease, and psoriasis may be less characteristic in its presentation, with a higher tendency to posterior pole involvement, bilaterality, and chronicity. Although acute anterior uveitis is grouped into the spectrum of human leukocyte antigen B27-related disease, other genetic and environmental factors including infections by gram-negative bacteria and gut inflammation can play a role in its pathogenesis. The prognosis of uveitis usually is excellent with topical treatment, and only those with posterior pole involvement or a high tendency to recur or to chronicity might benefit from immunosuppressive therapy.
 ...
PMID:Eye involvement in the spondyloarthropathies. 989 10

Our aim was to determine whether C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) is more appropriate in measuring disease activity in ankylosing spondylitis (AS). We studied 191 consecutive outpatients with AS in The Netherlands, France, and Belgium. Patients were attending secondary and tertiary referral centers. The external criterion for disease activity was: physician and patient assessment of disease activity on a visual analog scale (VAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). In each measure we defined 3 levels of disease activity: no activity, ambiguous activity, and definite disease activity. The patients with AS (modified New York criteria) were divided into 2 groups: those with spinal involvement only (n=149) and those who also had peripheral arthritis and/or inflammatory bowel disease (IBD) (n=42). For each criterion of disease activity, the patients with no activity and with definite activity were included in receiver operator curves and used to determine cutoff values with the highest sensitivity and specificity. We also calculated Spearman correlations. The median CRP and ESR were 16 mg/l and 13 mm/h, respectively, in the spinal group and 25 mg/l and 21 mm/h, respectively, in the peripheral/IBD group. In both groups the Spearman correlation coefficients between CRP and ESR were around 0.50. There was moderate to poor correlation between CRP, ESR, and the 3 disease activity variables (0.06-0.48). Sensitivity for both ESR and CRP was 100% for physician assessment and between 44 and 78% for patient assessment of disease activity and the BASDAI, while specificity was between 44 and 84% for all disease activity measures. The positive predictive values of CRP and ESR in our setting were low (0.15-0.69). We conclude that neither CRP nor ESR is superior to assess disease activity.
 ...
PMID:Relative value of erythrocyte sedimentation rate and C-reactive protein in assessment of disease activity in ankylosing spondylitis. 1022 32

We describe an HLA-B27 positive patient in whom posttraumatic pyogenic sacroiliitis led to complete unilateral sacroiliac joint ankylosis in the absence of any signs indicative of HLA-B27 associated spondyloarthropathy. Sacroiliitis is the pathologic hallmark - and usually one of the earliest pathologic manifestations - of ankylosing spondylitis (AS). Bilateral sacroiliitis is typical for ankylosing spondylitis. The frequency of asymmetric sacroiliitis may be higher in other inflammatory disorders, e.g., reactive arthritis, Reiters syndrome, spondylitis associated with psoriasis, or inflammatory bowel disease. Most but not all of these disorders show an increased prevalence among individuals who have inherited the HLA-B27 gene. In the context of this case, we discuss the differential diagnosis of unilateral sacroiliitis.
 ...
PMID:Sacroiliitis - it's not all B 27. 1050 21

Acute neutrophilic dermatosis, also referred to as Sweet's syndrome according to the first description in 1964, occurs not only as an isolated phenomenon but also in the context of neoplastic and inflammatory diseases, occasionally including arthritides. Recently Sweet's syndrome has been reported in a small number of patients with chronic inflammatory bowel disease, mostly in advanced stages of the disease. Here, we describe the sudden outbreak of acute neutrophilic dermatosis in coincidence with the onset of severe Crohn's disease (CD) in a patient with long-standing ankylosing spondylitis (AS). This condition has not been described before and therefore Sweet's syndrome should be added to the spectrum of skin manifestations the rheumatologist has to think about in the context of the spondylarthropathies (SpA). Furthermore, this case report is of interest because the skin lesions of Sweet's syndrome are somewhat similar to psoriasis, which is a rather frequent feature of the spondylarthropathies. This article intends to clarify the clinical and histological differentiation between Sweet's syndrome, psoriatic skin lesions and erythema nodosum for the rheumatologist and stresses that these conditions must each be treated in a completely different manner.
 ...
PMID:Sweet's syndrome in a patient with acute Crohn's colitis and longstanding ankylosing spondylitis. 1054 47

Inflammatory disease is associated with increased production of nitric oxide (NO) and activation of the inducible nitric oxide synthase (iNOS) pathway. Several studies have addressed the role of NO as a mediator of cytokine effects on bone cell activity in vitro. Stimulatory and inhibitory actions have been found, however, depending on the concentrations produced and model system used. In view of this, it has been difficult to predict whether increased production of NO during inflammation is likely to increase bone loss or prevent it. We have investigated the pathogenic role of NO in an animal model of inflammation-induced osteoporosis (IMO). NO production was increased in IMO when compared with controls (+344%; p < 0.01), and this was accompanied by activation of inducible NOS (iNOS) in the bone marrow space. Bone mineral density (BMD) was reduced in IMO when compared with controls (-64%; p < 0.01), and this was found to be associated with reduced osteoblast numbers (-44%; p < 0.05) and increased osteoclast numbers (+38%; p < 0.01). The NOS inhibitor L-NMMA reversed the deleterious effects of IMO on bone mass and bone turnover, but L-NMMA had no effect on bone mass in control animals. This study has important implications for many inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, and inflammatory bowel disease which are associated with increased NO production and osteoporosis. Our data not only suggest that iNOS activation and increased NO production contribute to the pathogenesis of osteoporosis in these situations, but also suggest that NOS inhibitors could be of therapeutic value in the prevention and treatment of such bone loss.
 ...
PMID:Evidence for a pathogenic role of nitric oxide in inflammation-induced osteoporosis. 1062 73

The aim of this study was to evaluate the clinical features, evolution and reliability of spondyloarthropathy criteria in a subset of patients with subclinical sacroiliitis and inflammatory bowel disease (IBD). All patients with IBD (n 62) attending a gastroenterology clinic from a referral centre were included to assess the prevalence of articular involvement. Patients were evaluated according to a specific protocol designed for the study, which included epidemiological and clinical variables, physical examination and radiological assessment. Only those with subclinical sacroiliitis were followed prospectively for 4 years. This group was visited every 6 months with the same initial protocol. Sacroiliac joints were studied using frontal and oblique X-ray views and graded according to New York criteria. HLA B27 typing was performed by serological methods in all patients and in 80 healthy controls. The reliability of Amor and ESSG criteria for spondyloarthropathy was evaluated. Fifteen patients (24%) presented with isolated subclinical sacroiliitis. In this group a higher frequency of peripheral arthritis and erythema nodosum was observed (p = NS compared to those without sacroiliitis). Most cases (60%) were grade II unilateral sacroiliitis. Three patients were HLA B27+ (p>0.05 compared to healthy controls). The resultant sensitivity of Amor's and ESSG criteria ranged from 40% to 46%. An unexpectedly high freuqency (9.5%) of psoriasis was observed in the whole group. There is a high prevalence of isolated subclinical sacroiliitis in IBD. This may represent a forme fruste of enteropathic ankylosing spondylitis, a stunted form of axial involvement because of therapy, or a third category of rheumatic disease associated with IBD. It may also represent a common characteristic of spondyloarthropathies, rather than a specific finding of IBD. The recently developed spondyloarthropathy criteria are not particularly helpful for the diagnosis of this milder form of spondyloarthropathy.
 ...
PMID:Subclinical sacroiliitis in inflammatory bowel disease: a clinical and follow-up study. 1114 53

Infiltrative diseases of the thyroid include systemic sclerosis, hemochromatosis, sarcoidosis, chondrocalcinosis and amyloidosis. Only rarely does thyroid amyloidosis result in clinically palpable goiter. Classically, amyloidosis is associated with tuberculosis, rheumatoid arthritis, multiple myeloma or inflammatory bowel disease. Only rarely does clinical amyloidosis develop in the setting of ankylosing spondylitis. We describe a case of amyloid goiter in a patient with ankylosing spondylitis-associated amyloidosis.
 ...
PMID:Amyloid goiter in a case of systemic amyloidosis secondary to ankylosing spondylitis. 1119 11

Rheumatoid arthritis (RA) is an autoimmune/inflammatory disorder with a complex genetic component. We report the first major genomewide screen of multiplex families with RA gathered in the United States. The North American Rheumatoid Arthritis Consortium, using well-defined clinical criteria, has collected 257 families containing 301 affected sibling pairs with RA. A genome screen for allele sharing was performed, using 379 microsatellite markers. A nonparametric analysis using SIBPAL confirmed linkage of the HLA locus to RA (P < .00005), with lambdaHLA = 1.79. However, the analysis also revealed a number of non-HLA loci on chromosomes 1 (D1S235), 4 (D4S1647), 12 (D12S373), 16 (D16S403), and 17 (D17S1301), with evidence for linkage at a significance level of P<.005. Analysis of X-linked markers using the MLOD method from ASPEX also suggests linkage to the telomeric marker DXS6807. Stratifying the families into white or seropositive subgroups revealed some additional markers that showed improvement in significance over the full data set. Several of the regions that showed evidence for nominal significance (P < .05) in our data set had previously been implicated in RA (D16S516 and D17S1301) or in other diseases of an autoimmune nature, including systemic lupus erythematosus (D1S235), inflammatory bowel disease (D4S1647, D5S1462, and D16S516), multiple sclerosis (D12S1052), and ankylosing spondylitis (D16S516). Therefore, genes in the HLA complex play a major role in RA susceptibility, but several other regions also contribute significantly to overall genetic risk.
 ...
PMID:A genomewide screen in multiplex rheumatoid arthritis families suggests genetic overlap with other autoimmune diseases. 1125 50

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.
 ...
PMID:Current use of biologicals for the treatment of spondyloarthropathies. 1133 71


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>