Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021390 (inflammatory bowel disease)
 23,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The epidermolysis bullosa acquisita (EBA) antigen is type VII collagen that is found within the anchoring fibrils of the basement membrane zone beneath stratified epithelia. Autoimmunity to the EBA antigen/type VII collagen has been associated with three diseases: EBA, bullous systemic lupus erythematosus (SLE) and a subset of linear IgA bullous diseases. Although some systemic diseases in which autoimmunity is thought to play a role (eg, inflammatory bowel disease, thyroiditis) have been reported in association with EBA, so far there have not been systemic diseases associated with autoimmunity to type VII collagen other than SLE. In the case of EBA and bullous SLE, it appears that many patients may have a genetic predisposition toward autoimmunity because they share a human leukocyte antigen (HLA) major histocompatibility (MHC) class II cell surface protein, HLA-DR2. The full clinical spectrum of EBA and perhaps other diseases in which there is an association with autoimmunity to type VII collagen is currently being defined.
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PMID:Autoimmunity to type VII collagen. 193 72

The major histocompatibility complex on the sixth chromosome controls expression of a complex series of cell surface antigens which comprise the human leukocyte antigen (HLA) system. These markers, beyond their importance in human organ transplantation, have been demonstrated to occur with an increased prevalence in certain disease states. The group of conditions showing the closest association with specific HLA antigens are the "spondyloarthropathies." These include ankylosing spondylitis (AS), Reiter's syndrome (RS), psoriatic arthritis (PsA), and the arthritis of inflammatory bowel disease (AIBD). Clinical and radiographic studies were made of 310 unrelated caucasoid patients with seronegative arthritis. HLA-A, B, C, and DR typing were performed using the microdroplet lymphocyte cytotoxicity test. Statistically increased prevalences of A26, B27, and Bw38 were observed, while B27 was associated with spinal involvement regardless of diagnosis (90 percent in AS p less than 0.0001). Experiments found A26 (23 percent p less than 0.001) and Bw38 (38 percent p less than 0.0001) in patients with PsA. Spondyloarthritis patients with spinal involvement who lacked B27 frequently had B7. The HLA DR typing for seven specificities was carried out in 196 patients. It was found that DRw4 (52 percent p less than 0.03) and DRw7 (39 percent p less than 0.04) were increased in the PsA patients. This study further confirms the close association of HLA antigens and the spondylarthropathies.
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PMID:The major histocompatibility complex. 695 Jun 86

The normal intestinal immune system is under a balance in which proinflammatory and anti-inflammatory cells and molecules are carefully regulated to promote a normal host mucosal defense capability without destruction of intestinal tissue. Once this careful regulatory balance is disturbed, nonspecific stimulation and activation can lead to increased amounts of potent destructive immunologica and inflammatory molecules being produced and released. The concept of balance and regulation of normal mucosal immune and inflammatory events is indicative of how close the intestine is to developing severe inflammation. The normal intestinal mucosal immune system is constantly stimulated by lumenal contents and bacteria. The stimulatory molecules present in the intestinal lumen that activate and induce subsequent mucosal immunologic and inflammatory events include bacterial cell wall products, such as peptidoglycans and lipopolysaccharides, as well as other chemotactic and toxic bacterial products that are produced by the many different types of bacteria within the gastrointestinal tract. These highly stimulatory bacterial cell wall products are capable of activating macrophages and T lymphocytes to release potent proinflammatory cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha). IL-1, IL-6, and TNF-alpha increase the presence of human leukocyte antigen (HLA) class II antigen-presenting molecules on the surfaces of epithelial cells, endothelial cells, macrophages, and B cells, thus increasing their ability to present lumenal antigens and bacterial products. The proinflammatory cytokines IL-1 and TNF-alpha also increase the ability of epithelial cells, endothelial cells, macrophages, and fibroblasts to secrete potent chemotactic cytokines, such as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), which serve to increase the movement of macrophages and granulocytes from the circulation into the inflamed mucosa. Thus, through lumenal exposure to potent, nonspecific stimulatory bacterial products, the state of activation of the intestinal immune system and mucosal inflammatory pathways are markedly up-regulated. This raises the question of whether there is a deficiency in effective down-regulation through the absence of normally suppressive cytokines such as interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), interleukin-4 (IL-4), and IL-1 receptor antagonist. Normally, the turning off of the active and destructive immunologic and inflammatory events should occur following the resolution of a bacterial or viral infection that has been appropriately defended against and controlled by the mucosal immune system. In inflammatory bowel disease (IBD), however, the down-regulatory events and processes that should turn off the immunologic and inflammatory protective processes, once the pathogenic agent has been cleared, appear to be deficient or only partially effective. We may find that we ultimately are dealing with disease processes that have more than one genetic or cellular basis. The improved understanding of the immunopathophysiology of IBD will allow exploration of novel immunologic and genetic approaches, such as gene replacement therapy, administration of a suppressor cytokine or an altered cell surface antigen, the administration of humanized monoclonal antibodies directed against proinflammatory cytokines, or the development of newer strategies against fundamental cell biologic mechanisms such as adhesion molecules.
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PMID:Alterations of the mucosal immune system in inflammatory bowel disease. 902 61

Class II antigens are strongly expressed on the inflamed colonic epithelium in inflammatory bowel disease. However, the mechanism of this epithelial class II antigen induction is not fully understood. Increased activities of interferon (IFN)gamma, tumor necrosis factor (TNF)alpha, and interleukin (IL)2 have been shown in the inflamed mucosa of inflammatory bowel disease. Therefore, we studied whether these cytokines could induce class II antigens on the human colonic epithelium. By an organ culture technique, 284 normal colonic biopsy specimens obtained from 49 individuals were cultured in media containing different concentrations of cytokines with/without anti-IFNgamma R antibody. Colonic epithelial class II antigens were identified by the indirect immunoperoxidase staining method with anti-human leukocyte antigen (HLA)-DR, DP, and DQ monoclonal antibodies. IFNgamma, TNFalpha, and IL2 induced epithelial class II antigens in 16 of 16 cases (100%), 2 of 16 cases (12.5%), and 6 of 17 cases (35%), respectively. Epithelial class II antigen expression in response to TNFalpha was induced via IFNgamma but not via IL2. This is the first demonstration that: (i) the induction of class II antigens on the colonic epithelium in response to TNFalpha is mediated via IFNgamma, and (ii) that IL2 induces class II antigens.
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PMID:Induction of major histocompatibility complex class II antigens on human colonic epithelium by interferon-gamma, tumor necrosis factor-alpha, and interleukin-2. 949 20

Azathioprine is a drug commonly used for the treatment of inflammatory bowel disease, organ transplantation and various autoimmune diseases. Hepatotoxicity is a rare, but important complication of this drug. The cases reported to date can be grouped into three syndromes: hypersensitivity; idiosyncratic cholestatic reaction; and presumed endothelial cell injury with resultant raised portal pressures, venoocclusive disease or peliosis hepatis. The components of azathioprine, 6-mercaptopurine and the imidazole group, may play different roles in the pathogenesis of hepatotoxicity. The strong association with male sex, and perhaps with human leukocyte antigen type, suggests a genetic predisposition of unknown type. Many of the symptoms of hepatotoxicity, such as nausea, abdominal pain and diarrhea, can be nonspecific and can be confused with a flare-up of inflammatory bowel disease. As well, the subtype resulting in portal hypertension can occur without biochemical abnormalities. A 63-year-old man with Crohn's disease who is presented developed the rare idiosyncratic form of azathioprine hepatotoxicity, but also had a severe disabling steroid myopathy, peripheral neuropathy, resultant deep venous thrombosis and pulmonary embolism related to immobility, and a nosocomial pneumonia. His jaundice and liver enzyme levels improved markedly on withdrawal of the drug, returning to almost normal in five weeks. Treating inflammatory bowel disease effectively while trying to limit iatrogenic disease is a continuous struggle. Understanding the risks of treatment is the first important step. There must be a low threshold for obtaining liver function tests, especially in men, and alertness to the need to discontinue the drug or perform a liver biopsy should patients on azathioprine develop liver biochemical abnormalities, unexplained hepatomegaly or signs of portal hypertension.
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PMID:Cholestatic hepatocellular injury with azathioprine: a case report and review of the mechanisms of hepatotoxicity. 981 67

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.
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PMID:Eye involvement in the spondyloarthropathies. 989 10

The concept of spondyloarthropathies gathers together a group of chronic diseases in which not only the locomotor system is involved but also other organs, especially the gastrointestinal tract. In humans, ileocolonoscopic studies demonstrated the presence of inflammatory gut lesions in all the diseases in the spondyloarthropathy group; their presence varied in the different diseases between 20% and 70%. The inflammation could be related to specific disease features in the spondyloarthropathies. Further research supports the hypothesis of subclinical inflammatory bowel disease in some patients with spondyloarthropathy, in which the locomotor inflammation was the only clinical manifestation. The link between gut inflammation and arthropathy has also been demonstrated in animal models, notably the human leukocyte antigen B27 transgenic rats. The temporal relationship between activity and severity of colonic involvement and flares of peripheral arthritis directs treatment of choice. For all forms of enterogenic arthropathies, nonsteroidal anti-inflammatory drugs remain the acute treatment form. Caution is in order, however, because of their possible harmful effects on intestinal integrity, permeability, and even on gut inflammation.
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PMID:Bowel inflammation and the spondyloarthropathies. 989 11

Inflammatory bowel disease (IBD) is characterized by a chronic relapsing intestinal inflammation, typically starting in early adulthood. IBD is subdivided into two subtypes, on the basis of clinical and histologic features: Crohn disease and ulcerative colitis (UC). Previous genomewide searches identified regions harboring susceptibility loci on chromosomes 1, 3, 4, 7, 12, and 16. To expand our understanding of the genetic risk profile, we performed a 9-cM genomewide search for susceptibility loci in 268 families containing 353 affected sibling pairs. Previous linkages on chromosomes 12 and 16 were replicated, and the chromosome 4 linkage was extended in this sample. New suggestive evidence for autosomal linkages was observed on chromosomes 1, 6, 10, and 22, with LOD scores of 2.08, 2.07, 2.30, and 1.52, respectively. A maximum LOD score of 1.76 was observed on the X chromosome, for UC, which is consistent with the clinical association of IBD with Ullrich-Turner syndrome. The linkage finding on chromosome 6p is of interest, given the possible contribution of human leukocyte antigen and tumor necrosis-factor genes in IBD. This genomewide linkage scan, done with a large family cohort, has confirmed three previous IBD linkages and has provided evidence for five additional regions that may harbor IBD predisposition genes.
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PMID:A genomewide analysis provides evidence for novel linkages in inflammatory bowel disease in a large European cohort. 1005 16

Inflammatory bowel disease (IBD) is a multifactorial disorder with unknown etiology and pathogenesis. DA-6034, 7-carboxymethyloxy-3', 4', 5-trimethoxy flavone, is a synthetic flavonoid known to possess anti-inflammatory activity. This study was performed to evaluate the oral therapeutic effect of DA-6034 in three experimental animal models of IBD: two chemical-induced IBD models of rats and the human leukocyte antigen (HLA)-B27 transgenic rat model known to develop spontaneous colitis without the use of exogenous agents. Acute chemical colitis was induced by intracolonic instillation of 1.2 ml of 4% acetic acid solution. Prednisolone (1 mg/kg), sulfasalazine (100 mg/kg) and DA-6034 (0.3 to approximately 3 mg/kg) were orally administered twice daily for 6 days in these rats. In addition, chronic chemical colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid (TNBS) 30 mg in 50% ethanol and agents were orally administered for 6 or 20 days. In chemical-induced IBD models, all of these agents reduced the severity of colitis and specially, DA-6034 (3 mg/kg) showed more potent effect than other drugs in macroscopic lesion score. In HLA-B27 transgenic rats, DA-6034 (3 mg/kg) and prednisolone (0.5 mg/kg) were treated orally twice daily for 6 weeks. The HLA-B27 transgenic rats showed only mild colitis, compared with the chemical-induced colitis models. DA-6034 ameliorated the loose stool and decreased microscopic damage, which is the important indicator of this model. In conclusion, oral therapy of DA-6034 attenuated the macroscopic and histologic damages of the colon in all three experimental models of IBD, which suggest that DA-6034 could be a promising drug in the treatment of IBD.
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PMID:Effect of DA-6034, a derivative of flavonoid, on experimental animal models of inflammatory bowel disease. 1048 73

The etiology of primary sclerosing cholangitis remains unknown. Bacteria, toxins, viral infections, and immunological and genetic factors have all been proposed as etiological agents. Portal bacteremia, toxins absorbed from the diseased colon in inflammatory bowel disease, and cytomegalovirus and reovirus infections have been implicated by various investigators but there is little evidence to support these hypotheses. The close association between primary sclerosing cholangitis and various human leukocyte antigen haplotypes is now well established and lends support to the theory that immunologic and genetic mechanisms may be involved in its pathogenesis. Patients with primary sclerosing cholangitis may have elevated levels of circulating immune complexes, immunoglobulins, and non-organ specific autoantibodies. The association between ulcerative colitis and primary sclerosing cholangitis remains unexplained and both groups of patients have a high prevalence of antibodies to the perinuclear cytoplasmic antigen. The long-term prognosis in primary sclerosing cholangitis is tempered by the development of cholangiocarcinoma in 6%-30% of patients when followed over long periods of time. Detecting cholangiocarcinoma early in a patient with primary sclerosing cholangitis is one of the most frustrating problems faced by a clinician while caring for these patients. The long-term outlook for patients with primary sclerosing cholangitis and cholangiocarcinoma remains dismal, whatever the treatment modality employed. However, the development of a multivariate statistical survival model from long-term survival data from the Mayo Clinic and other centers has been a major step in identifying individual primary sclerosing cholangitis patients at low, moderate, and high risk of dying. Such models have been useful for stratifying patients in therapeutic trials, for in patient counseling, and in patient selection and timing of liver transplantation.
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PMID:Etiology and natural history of primary sclerosing cholangitis. 1066 79


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