Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recognition of MHC + peptide complexes by TCRs is thought to involve a large surface formed by exposed residues from the bound peptide and from the alpha-helices of the MHC protein. This interaction appears to be essentially symmetrical in the positioning of the TCR relative to the MHC molecule. In this study the topology of HLA-B27 recognition by an alloreactive TCR, 64.8P, has been analyzed with a panel of site-specific mutants that have changes at multiple positions along the peptide binding site of HLA-B27. Abrogation of transfectant target cell lysis by CTL 64.8P was obtained only with some mutations in the peptide side chain binding pockets A and B, whereas little or no effect was observed with mutations outside these pockets. CTL 64.8P efficiently lysed murine transfectant cells, including HLA-B27+ RMA-S cells. Recognition of this latter transfectant was more efficient upon increased HLA-B27 expression at 26 degrees C. The uneven distribution of mutations affecting HLA-B27 allorecognition by CTL 64.8P strongly suggests an asymmetrical topology in the interaction of this TCR with HLA-B27, in which most of the binding energy is provided by contacts with HLA-B27 and/or peptide residues located close to pockets A and B, with little contribution from other areas of the MHC or peptide molecules. Its conservation in RMA-S cells further suggests that the epitope recognized by CTL 64.8P is either peptide-independent or requires any of a set of peptides having the same amino-terminal residues.
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PMID:Unusual topology of an HLA-B27 allospecific T cell epitope lacking peptide specificity. 751 Jul 42

Reactive arthritis, or Reiter's disease, characteristically affects the joints of the lower limbs in an asymmetrical pattern. Usually it does not affect the cervical spine, and atlantoaxial subluxations are the exception. This paper describes the case of an HLA-B27-positive female patient with a sexually acquired reactive arthritis where a non-reducible atlantoaxial subluxation was present. The patient was followed from age 27 to 41. By the age of 38, an anterior decompression of the cervico-medullary junction was performed by a transoral approach; in a second stage, the patient underwent an occipito-cervical posterior fusion. The pathological study revealed a non-specific and chronic inflammatory infiltrate.
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PMID:Reactive arthritis with a severe lesion of the cervical spine. 911 53

Psoriasis usually occurs many years before development of arthritis. This is a case report of a patient with acute polyarthritis affecting both peripheral joints and the left sacroiliac joint, preceding the appearance of typical skin manifestations for almost two months. A 44-year-old male mechanic was admitted to our institution for acute additive polyarthritis. Inflammatory synovitis primarily affected large peripheral joints (knees, ankles) in an asymmetrical pattern, with a concomitant development of unilateral sacroiliitis and later with asymmetrical involvement of several proximal and distal interphalangeal joints of the hands and feet. There were also signs of enthesopathy of the right heel. Arthritis was not proceeded by infection of the lower genital or gastrointestinal tract or serological and bacteriological evidences of streptococcal or HIV infection. Laboratory findings showed an erythrocyte sedimentation rate (92 in the first hour), positive histocompatibility antigen HLA-B27 and an increased level of acute phase reactants. Almost two months after affecting the locomotor system a typical psoriatic rash developed, first affecting the scalp and then spreading over the trunk and extremities. It was accompanied by severe onychodystrophy. The patient underwent intensive treatment with methylprednisolone (1.5 mg/kg) and cyclosporine A with significant results.
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PMID:[Psoriatic arthritis: case report of acute HLA-B27 positive polyarthritis preceding the onset of typical skin changes]. 947 36

During a 7 year-period 9 children (7 boys, 2 girls) with juvenile reactive arthritis (JReA) due to Salmonella enteritidis (Se) were prospectively studied because of an unusual type of onset and/or course of the disease. The mean duration of JReA activity was 9 +/- 3.6 months. The mean follow-up time was 55.2 +/- 17.4 months. JReA presented as any of the three types of juvenile chronic arthritis (JCA), namely, as asymmetrical oligoarthritis, polyarthritis, or systemic JCA in 5, 2, and 2 patients respectively. Two patients had pericarditis and three developed the complete or incomplete Reiter's syndrome during the disease or during a recurrence. Five patients carried the HLA-B27 and 3/5 developed psoriatic lesions 1 to 15 months after the onset of JReA. The presence of HLA-B27 and psoriasis was associated with a more prolonged course of JReA. However, no patient developed late radiological lesions or sacroiliitis during follow-up.
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PMID:Persistent or severe course of reactive arthritis following Salmonella enteritidis infection. A prospective study of 9 cases. 985 13

HLA-B27 is highly linked with a group of human diseases called spondyloarthropathies (SpA). Many of these disorders begin after an infection with an enterobacteria. The symptoms seen in patients with spondyloarthropathies are inflammatory pain in the spine and asymmetrical arthritis of lower limbs. Additional symptoms related to SpA include inflammation in the eyes, bowel, and skin. The autoantigen(s) in SpA are not known. Proteins such as collagen and proteoglycans have been thought to be potent autoantigens in arthritidis including B27-associated human diseases. Type II collagen is a common denominator among eyes and joints, affected tissues in B27-linked diseases. Moreover, a few reports indicated CII specific T cells and antibodies in patients with spondyloarthropathies. We and others have previously described development of spontaneous arthritis and nail disease in HLA-B27 transgenic animals. To determine whether CII may be a target antigen in the B27-linked diseases, B27 + m beta 2 m% (HLA-B27) transgenic mice lacking mouse beta 2m with and without human beta 2m) mice were immunized with type II collagen inside the barrier facility. Male HLA-B27 transgenic mice developed collagen-induced arthritis compared to transgene negative littermates or female counterparts. There was no difference in the incidence of arthritis in HLA-B27 transgenic mice with and without human beta 2m. Our data suggest that beta 2m free heavy chain of HLA-B27 may present soluble antigens such as type II collagen to trigger specific T cells contributing in the development of arthritis. Our data also suggest that CII may be a potential target antigen in the cartilage during the disease process.
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PMID:HLA-B27 transgenic mice are susceptible to collagen-induced arthritis: type II collagen as a potential target in human disease. 1071 6

In adults, reactive arthritis (ReA) following Clostridium difficile-enterocolitis has been documented. In children, only one case of C. difficile-associated ReA has been reported. We now describe two other cases of ReA associated with C. difficile in children. The characteristics of ReA due to C. difficile appear to be similar in adults and children. Both children show polyarthritis after an episode of diarrhoea with positive stool cultures for C. difficile. Arthritis is asymmetrical with a self-limiting course. Nonsteroidal antiinflammatory drug (NSAID) therapy is sufficient. One case is remarkable because of its prolonged course of ReA despite NSAID therapy, and its association with the presence of HLA-B27 antigen.
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PMID:Clostridium difficile-associated reactive arthritis in two children. 1476 23

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.
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PMID:Concepts and epidemiology of spondyloarthritis. 1677 73

This is a cross-sectional study that analyzed the pattern and frequency of articular and ophthalmologic manifestations in patients with Crohn's disease (CD) and ulcerative colitis (UC), with or without signs of active bowel inflammation. One hundred and thirty consecutive patients with CD (n = 71) and UC (n = 59) were examined. Simple X-rays of lumbar spine, sacroiliac joints, and calcaneal bone were performed and human leukocyte antigen (HLA)-B27 was typed. Joint manifestations occurred in 41 (31.5%) patients, 27 (38%) with CD and 14 (23.7%) with UC. Peripheral involvement occurred in 22 patients, axial involvement in five, and mixed involvement in 14. The most frequently involved joints were knees (56.1%), ankles (29.3%), and hips (29.3%), while the predominant pattern was oligoarticular (84.6%) and asymmetrical (65.6%). Enthesitis was identified in seven (5.4%) patients and inflammatory lumbar pain in 13 (10%). Eight of these patients fulfilled the diagnostic criteria for ankylosing spondylitis (6.2%). Radiographic sacroiliitis occurred in 12 patients (9.2%). Ocular abnormalities were present in six patients (6.2%), and HLA-B27 was positive in five (5.8%). In conclusion, the articular manifestations in the present study were predominantly oligoarticular and asymmetric, with a low frequency of ophthalmologic involvement and positive HLA-B27.
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PMID:A cross-sectional study of 130 Brazilian patients with Crohn's disease and ulcerative colitis: analysis of articular and ophthalmologic manifestations. 1809 11

Joint involvement associated with inflammatory bowel disease (IBD) belongs to the concept of spondyloarthritis (SpA) and includes two types of arthritis: a peripheral arthritis characterized by the presence of pauciarticular asymmetrical arthritis affecting preferentially joints of lower extremities and an axial arthropathy including inflammatory back pain, sacroiliitis and ankylosing spondylitis (AS). Treatment of arthritis includes a short-term use of NSAIDs associated with optimized treatment of gut inflammation. Safety concerns mean that long-term treatment with NSAIDs is best avoided if possible. Salazopyrine can be recommended for treatment of peripheral arthritis. Methotrexate and azathioprine are generally ineffective. Finally, efficacy of anti-TNF therapy (infliximab and adalimumab) is well established. However, use of etanercept is not recommended because of the increased risk for intestinal disease relapse. Pathogenesis of gut-joint iteropathy is not elucidated. Both inflammations are tightly related as suggested by human evidence of gut inflammation in patients with other forms of SpA and animal evidence of gut and joint inflammation in HLA-B27/human beta(2)-microglobulin transgenic rat model and TNF(DeltaARE) mice. Several clues for the linkage between gut and joint inflammation have been put forward including an altered recognition and handling of bacterial antigens, an aberrant trafficking of CD8+ T cells with an impaired T-helper type 1 cytokine profile and expression of aEb7 integrin, an altered trafficking of macrophages expressing CD163 and evidence of an increased angiogenesis. A transcriptome analysis of mucosal biopsies identified a set of 95 genes that are differentially expressed in both CD and SpA as compared with healthy controls suggesting common pathways. TNF plays a key role in the pathogenesis of various arthritic diseases and IBD. Mesenchymal/myofibroblast-like cells may represent the local primary targets of TNF in the induction of gut and joint pathology. Selective expression of TNFRI on these cells seems to be sufficient to orchestrate the complete development of SpA-related pathologies at least in TNF(DeltaARE) mice. Finally, genetic susceptibility is probably required to develop these pathologies. Genotyping of AS patients provided evidence for an important overlap between determinants of inherited predisposition to CD and AS. The best documented common association is with an IL-23R polymorphism, although the exact role remains unexplored. In addition, evidence suggests that a number of recently identified CD-susceptibility loci are associated with AS. Clinical, genetical, immunological and therapeutic evidence support the tight junction between gut and joint inflammation in two linked diseases, IBD and SpA, belonging to the 'immune-mediated inflammatory diseases'.
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PMID:Joint involvement associated with inflammatory bowel disease. 1989 67

Reiter's syndrome (RS) is a major rheumatic disease, which is frequently chronic, often difficult to treat, and can cause significant, longterm morbidity. To date, there is no specific diagnostic test for RS. Therefore diagnosis has to be made by clinical acumen. Because of the venereal origin of most cases of RS, urethritis and/or cervicitis are often found. If absent, a thorough search should be made for other extra-articular features, e.g., diarrhea, conjunctivitis and mucocutaneous lesions. The condition afflicts mainly young men, but is becoming increasingly more common in women and is seen even in children. The arthritis associated with RS usually is oligoarticular, asymmetrical and tends to involve the lower extremities. However, extra-articular manifestations may be absent. If they are, a positive HLA-B27 test may be helpful, because 65-80% of Caucasians who develop RS are positive for HLA-B27.
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PMID:Current Concepts of Reiter's Syndrome. 2128 75


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