Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010346 (Crohn's disease)
 21,615 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to determine immunogenetic markers of susceptibility in Crohn's disease (CD), taking the different features of the clinical course of the disease into account. HLA class I, HLA class II and TAP transporter gene polymorphisms were studied using DNA typing methods. Gene and antigen frequencies were analysed and compared in a group of 102 CD patients and 200 unrelated healthy controls from the same area. Analysis of the whole CD patient population revealed no definite association with either HLA or TAP gene alleles, with the exception of an association with DRB1*1302 (Pc < 0.05). However, when clinical subgroups of patients were considered, specific associations with some genetic markers were found. The most definitive results involved a genetic association in the group of patients who did not respond to glucocorticoid therapy. This group was characterized by a high frequency of HLA-DRB1*04 (P < 0.05). Conversely, a positive association with the TAP2-A allele was found in cortico-responder patients (Pc < 0.03). Furthermore, analysis of the distribution of HLA class II alleles in relation to the presence of extra-intestinal manifestations revealed an association with the DQB1*0501 or *0503 suballele of DQ5 (P < 0.05). Finally, patients with lesions in the small bowel were more frequently HLA DRB1*07 (P < 0.05). The present study supports the concept of clinical heterogeneity in Crohn's disease associated with a background of genetic heterogeneity.
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PMID:Investigation of the association of major histocompatibility complex genes, including HLA class I, class II and TAP genes, with clinical forms of Crohn's disease. 873 77

GM and KM immunoglobulin (Ig) allotypes and their interactions with HLA antigens have been analyzed in various autoimmune diseases: multiple sclerosis, rheumatoid arthritis, insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus, coeliac disease, Crohn's disease, Graves' disease, atrophic thyroiditis, Hashimoto's thyroiditis, myasthenia gravis, chronic active hepatitis, alopecia areata, uveitis, vitiligo, Turner's syndrome, glomerular nephritis, Berger's disease and idiopathic dilated cardiomyopathy. This review reports published results about associations or linkages, as well as the origins of the populations, the numbers of patients and controls tested. The possible role of Ig polymorphisms in the physiopathology of autoimmune diseases is discussed. Ig allotypes and statistical methods used to analyse the HLA and Ig data are also described.
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PMID:Immunoglobulin allotypes (GM and KM) and their interactions with HLA antigens in autoimmune diseases: a review. 878 16

It is increasingly recognized that chronic Ag exposure may lead to clonal expansions of T cells, including those within the peripheral blood. Inflammatory bowel disease is a chronic, multisystemic disease of unknown origin that predominantly affects the intestine. We sought to determine whether clonal expansions of T cells are present in the peripheral blood of patients with inflammatory bowel disease by an examination of TCR usage. Positively selected CD4+ and CD8+ peripheral blood T cells were isolated from subjects with active ulcerative colitis, Crohn's disease, and diverticulitis and from normal controls. Analysis of complementarity determining region 3 lengths of 24 TCR-beta chain V region families from CD4+ and CD8+ peripheral blood T cells showed a skewed distribution in the three inflammatory groups, consistent with expansion of T cell clones, in comparison to the normally distributed pattern observed among the control donors. Random sequencing of the PCR amplification products of CD4+ peripheral blood T cells from the subjects with ulcerative colitis, Crohn's disease, and diverticulitis revealed reiterative TCR-beta chain sequences that were not found in the normal donors. In subjects with Crohn's disease, the reiterative TCR-beta chain sequences from the CD4+ peripheral blood T cells were persistent over at least a 1-yr period. The persistently expanded TCR-beta chain sequences of CD4+ peripheral blood T cells were identifiable in genomic DNA isolated from archival tissue of intestine from subjects with Crohn's disease and ulcerative colitis by Southern blotting and direct DNA sequencing. An identical twin pair, concordant for Crohn's disease, shared the same reiterative TCR-beta chain sequences in their CD4+ peripheral blood T cells. These studies show that chronic intestinal inflammation is associated with expansions of CD4+ peripheral blood T cells. Furthermore, in inflammatory bowel disease these T cell clonal expansions are persistent and shared among HLA-identical individuals, implicating a response to specific, persistent, and stimulating Ags in these diseases.
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PMID:Persistent clonal expansions of peripheral blood CD4+ lymphocytes in chronic inflammatory bowel disease. 881 32

A number of studies have demonstrated aggregation of cases of ulcerative colitis or Crohn's disease in families, and of cases of both diseases within the same families, suggesting that patients share a genetic background. Perhaps because of differences in the selection of patients, study design and diagnostic criteria, different patterns of occurrence of inflammatory bowel disease (IBD) have been found among relatives of patients with these disorders. In recent years, however, several studies have been carried out, aiming by epidemiological methods to reveal (1) the frequency of familial occurrence of IBD among patients with ulcerative colitis and Crohn's disease, and (2) the prevalence of IBD among 1(0) relatives to patients with these diseases. Results from these studies show a relatively uniform pattern of family occurrence in about 10% of patients with ulcerative colitis and Crohn's disease, and a prevalence among 1(0) relatives of about 10 times that of the background population. A twin study reported a significantly higher concordance rate for Crohn's disease than for ulcerative colitis in monozygotic twins. By use of complex segregation analyses in 3 different studies, a very similar model of inheritance was found to fit for ulcerative colitis, namely a major dominant or additive gene with a low penetrance. For Crohn's disease the best-fitting model was a major recessive gene, with a high penetrance. This difference strongly supports the concept of ulcerative colitis and Crohn's disease as two separate disease entities. The occurrence of both diseases within the same families in certain members of the affected families is difficult to explain. The search for distinct associations of HLA genes with inflammatory bowel disease has shown a positive correlation between DR2 and ulcerative colitis and a negative association with DR4 and DRw6, compared with ethnically matched controls. In contrast, in Crohn's disease a positive association with the combination of DR1 and DQw5 alleles was revealed, thus indicating genetically different disease susceptibility for the two disorders. In general, however, no consistent pattern has been revealed from studies of association of HLA-A or -B antigens or blood group and serum protein markers. In two French families with several members affected with Crohn's disease no evidence for an HLA haplotype association could be revealed. Possible inherited markers of ulcerative colitis or Crohn's disease have been sought but without convincing success. Increased intestinal permeability, presence of anticolon antibodies and presence of antineutrophil leukocyte antibodies have been proposed, but not proved. Thorough studies are now needed of multimember families with disease for linkage studies to identify loci which contribute to increased liability. Such studies are in progress in different centres.
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PMID:Familial occurrence and inheritance studies in inflammatory bowel disease. 881 99

We reviewed the experience with allogeneic bone marrow transplantation (BMT) at Fred Hutchinson Cancer Research Center and affiliated Seattle hospitals for patients with preexisting autoimmune diseases. The review was limited to patients who received transplants between 1969 and 1989 from a related donor and who had at least 3 years of relapse-free survival. Of 901 evaluable patients, 11 were identified with a preexisting autoimmune disease and 2 with diseases that were possibly autoimmune in nature. Pretransplant diseases identified in this review included rheumatoid arthritis (n = 1), discoid or systemic lupus (n = 2), insulin dependent Type 1 diabetes (n = 3), hyperthyroidism (n = 4), dermatitis herpetiformis (n = 1), vasculitis (n = 1), and Crohn's disease (n = 1). All 13 patients survive with a median followup of 14 (range, 7-20) years after transplantation from an HLA identical sibling (n = 10), parent (n = 1) or identical twin (n = 2). Pre and post-transplant histories are presented. Variables to be considered in the assessment of any beneficial effect of BMT are discussed, including consideration of different patterns of activity that describe the natural history of various autoimmune diseases. Although autoimmune disease did not recur after allogeneic BMT in these 13 patients, disease and post-transplant variables may confound the interpretation of results from retrospective analysis.
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PMID:Pre-existing autoimmune disease in patients with long-term survival after allogeneic bone marrow transplantation. 915 Jan 14

We report two cases of rheumatoid arthritis (RA) associated with Crohn's disease (CD). The first case was a 60-year-old man with longstanding CD who next developed a seropositive, nodular RA. This patient also had bilateral sacroiliitis, but without positive HLA B27. The second was a 65-year-old female with a 15-year history of seropositive RA who presented secondarily a CD. No sacroiliitis or nodules were found in this patient. Both patients were DR1 (DRB1* 0101). Gold salts were only given in the second case and were stopped many years before the gastrointestinal symptoms. A similar case report has been previously described consisting in an ulcerative colitis complicating a seronegative HLA-B27 RA with sacroiliitis. The gastrointestinal involvement in RA may be broad and includes many causes: drug-induced colitis (including gold enterocolitis) vasculitis and amyloidosis located in the gut, associated bowel disease such as collagenous colitis, and also infectious agents. In addition, erosive polyarthritis associated with gastrointestinal manifestations can present a problem in the differential diagnosis between RA and an enteropathic arthritis. Finally, the coexistence by chance of inflammatory bowel disease and RA is suggested by the low occurrence of these two conditions in the same patient.
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PMID:Crohn's disease associated with seropositive rheumatoid arthritis. 917 28

In a 12.5 cM genome-wide scan for psoriasis susceptibility loci, recombination-based tests revealed linkage to the HLA region (Zmax = 3.52), as well as suggestive linkage to two novel regions: chromosome 16q (60-83.1 cM from pter, Zmax = 2.50), and chromosome 20p (7.5-25 cM from pter, Zmax = 2.62). All three regions yielded P values < or = 0.01 by non-parametric analysis. Recombination-based and allele sharing methods also confirmed a previous report of a dominant susceptibility locus on distal chromosome 17q (108.2 cM from pter, Zmax = 2.09, GENEHUNTER P = 0.0056). We could not confirm a previously reported locus on distal chromosome 4q; however, a broad region of unclear significance was identified proximal to this proposed locus (153.6-178.4 cM from pter, Zmax = 1.01). Taken together with our recent results demonstrating linkage to HLA-B and -C, this genome-wide scan identifies a psoriasis susceptibility locus at HLA, confirms linkage to 17q, and recommends two novel genomic regions for further scrutiny. One of these regions (16q) overlaps with a recently-identified susceptibility locus for Crohn's disease. Psoriasis is much more common in patients with Crohn's disease than in controls, suggesting that an immunomodulatory locus capable of influencing both diseases may reside in this region.
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PMID:Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan. 925 83

We report on a 39-year-old man with Crohn's disease who was admitted with cardiogenic shock after a short history of progressive dyspnea. Echocardiographic examination (transthoracic echocardiography) showed severe aortic regurgitation, mild mitral regurgitation, and enlargement of the sinus of Valsalva and of the ascending aorta at the level of the right pulmonary artery. The left ventricular ejection fraction was 30%. After aortic valve replacement, histologic examination of the ascending aorta showed chronic aortitis resembling syphilitic aortitis (serology for syphilis was negative) and HLA B27 related aortitis. The aortic valve showed deformation and thickening of the cusps by fibrous tissue without evidence of endocarditis. The patient remained well after surgery and echocardiographic examination 6 months later showed normal function of the aortic valve prosthesis. The diameter of the sinus of Valsalva and of the ascending aorta was slightly bigger, possibly indicating ongoing destruction. The left ventricular ejection fraction nearly normalized. It seems possible that this type of aortitis, characterized by its proximity to the valve ring, is another extraintestinal cardiac manifestation of Crohn's disease. The possibility of ongoing destruction of the sinus of Valsalva and of the ascending aorta after valve replacement makes regular echocardiographic control necessary.
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PMID:[Aortic valve insufficiency in Crohn disease]. 928 21

Despite extensive research, the cause of Crohn's disease remains unknown. No specific infectious agent has been identified, though interest has been focused on the possible involvement of mycobacteria, and recently on child hood measles as a possible aetiological factor. Both hereditary and environmental factors seem to contribute to development of the disease. The clinical picture may be dependent upon individual HLA subtypes, as they appear to differ from each other regarding the secretion of inflammatory cytokines. Non-invasive scintigraphy and computerised tomography are used to determine the extent of disease, and to localise such complications as abscesses and fistulas. Endoscopic ultrasonography and magnetic resonance imaging have proved particularly valuable in diagnosing rectal and rectovaginal fistulas. New 5-ASA (5-aminosalicylic acid) preparations, steroids with fewer systemic side effects, and azathioprine-induced immunosuppression constitute the cornerstones of medical treatment, further developments in pharmacological immunoregulation being a future treatment possibility.
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PMID:[Certain immune-genes may affect Crohn disease. Advances in diagnosis, pathogenesis and treatment]. 949 65

Inflammatory bowel disease (IBD) is commonly associated with arthritic manifestations. They are divided into three clinical categories; peripheral arthritis, spondylitis, and sacroiliitis. To evaluate the incidence of arthritis associated with IBD in Korea, we retrospectively reviewed one hundred and twenty-nine patients with IBD, 77 with ulcerative colitis (UC) and 52 with Crohn's disease (CD). Arthritis occurred in twenty-two patients (17.1%); 15 with UC(19.6%), 7 with CD (13.5%). Patients with arthritis had more active inflammations and all were seronegative except one patient. Peripheral arthritis was found in twenty patients (15.5%) and more common in UC (19.6%) than in CD (9.6%). Joint involvements tended to be monoarticular or pauciarticular, and most frequently developed in the knee and ankle. Spondylitis was diagnosed in one patient (1.6%) who showed HLA B27 positivity. Radiographic sacroiliitis was observed in eight patients (6.2%) who revealed HLA B27 negativity. Both peripheral arthritis and sacroiliitis were found in six patients (4.6%). In CD, arthritis occurred in 20% of the patients with colonic involvement but in none of the patients without colonic involvement. In conclusion, arthritis was frequent in patients with IBD. Peripheral arthritis was more common in patients with UC than CD. All the patients with CD and arthritis had colonic involvement.
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PMID:Arthritic manifestations of inflammatory bowel disease. 953 17


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