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)

Isolation of antigenic peptides from the MHC-groove has contributed to the understanding of T cell responses. However, these MHC-associated peptides have been isolated from various murine and human cell lines. The specific antigen responsible for the pathogenesis of inflammatory bowel disease is unknown. We examined antigenic peptides bound to the class II major histocompatibility complex (MHC) groove in human intestine by ion-trap tandem mass spectrometry equipped with online reverse-phase high performance liquid chromatography. We detected 55 parent proteins from 4 controls, 9 patients with ulcerative colitis, and 9 patients with Crohn's disease. The calculated molecular masses (m/z) of these peptides ranged from 874.4 to 2727.4, representing 10-26 amino acid residues. Fifty-one of these 55 parent proteins were exogenous proteins. Escherichia coli-, Saccharomyces cerevisiae-, and Caenorhabditis elegans-derived peptides were found frequently in patients with inflammatory bowel disease. The present results suggest that in vivo antigen processing by antigen-presenting cells and T lymphocytes in human intestine participate with exogenous antigen presentation. Increased immune responses against E. coli, S. cerevisiae and C. elegans found in patients with inflammatory bowel may participate as dysregulated immune responses to enteric flora in the pathogenesis of inflammatory bowel disease.
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PMID:Analysis of intestinal HLA-DR bound peptides and dysregulated immune responses to enteric flora in the pathogenesis of inflammatory bowel disease. 1246 27

Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. Genetic factors implied on its onset and severity may include genes located within the class II major histocompatibility complex (MHC) region. The aim of this study was to determine the relationship between human leukocyte antigen (HLA)-DRB1 alleles with the clinical disease patterns of UC in Mexican Mestizo patients. High-resolution HLA typing was performed by polymerase chain reaction-sequence specific oligonucleotide (PCR)-SSO reverse dot blot and PCR-single-strand polymorphism in 67 patients with UC and 99 ethnically matched healthy controls. UC patients overall showed an increased frequency of HLA-DR1 as compared with healthy controls (17.1% versus 5%, [pC = 0.003, OR = 3.9]). Patients with extensive colitis showed increased frequencies of HLA-DR1 (pC = 1 x 10(-10), OR = 13.9), HLA-DRB1*0103 (pC = 1 x 10(-3), OR = 21.7), HLA-DRB1*0102 (pC = 0.007, OR = undetermined), and HLA-DR15 (pC = 1 x 10(-3), OR = 8.5) when compared with healthy controls. We also found a statistically increased frequency of HLA-DR15 in UC patients with extensive colitis compared with UC patients with only distal colitis (18.7% versus 1.8%, pC = 0.03; OR = 12.2). When patients who underwent proctocolectomy were compared with those who did not, an increased frequency of HLA-DRB1*0103 was observed (21.8% versus 4.9%; pC = 0.03; OR = 5.4; 95% confidence interval, 1.39-21.93). Also, patients with proctocolectomy showed increased frequencies of HLA-DR1 (pC = 1 x 10(-3), OR = 24.2) and HLA-DRB1*0103 (pC = 1 x 10(-3), OR = 50.6) when compared with healthy controls. We concluded that HLA-DR1 is associated with genetic susceptibility to UC in the Mexican Mestizo population. HLA-DR15 distinguishes a subgroup of patients with extensive colitis and the HLA-DRB1*0103 allele distinguishes a subgroup of severe form of disease that might require surgical management.
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PMID:Clinical and genetic heterogeneity in Mexican patients with ulcerative colitis. 1250 22

The aim of this study was to identify major histocompatibility complex alleles associated with the development and clinical features of inflammatory bowel disease (IBD). Genotyping at the human leukocyte antigen (HLA) DRB1 and DQB1 loci was performed on individuals from 118 Caucasian IBD sibling pair families and on 216 healthy controls. Both population- and family-based association tests were used to analyze data obtained on the entire study population and on clinical subgroups stratified by diagnosis, ethnicity, and disease distribution. HLA DRB1*0103 was significantly associated with IBD (OR = 6.0, p = 0.0001) in a case-control analysis of non-Jewish IBD-affected individuals. This association was apparent among both Crohn's disease (OR = 5.23, p = 0.0007) and ulcerative colitis (OR = 7.9, p = 0.0001) patients and was confirmed in the non-Jewish IBD population by results of family-based association analysis using the transmission disequilibrium test. HLA DQB1*0501 was also associated with IBD (OR = 1.64, p = 0.02) in the non-Jewish population. but statistically significant association of this allele with disease was not detected for Crohn's disease and ulcerative colitis separately. No significant associations were identified among the Jewish patients. In the non-Jewish IBD families, IBD was as strongly associated with the DRB1*0103 DQB1*0501 haplotype as with the DRB1*0103 allele alone. The carrier frequency of the DRB1*0103 allele was found to be 10-fold higher in Crohn's disease patients with pure colonic involvement than in healthy controls (38.5% vs. 3.2%; p = 0.0002). These data demonstrate the association of the HLA DRB1*0103 allele with both Crohn's disease and ulcerative colitis and with large intestine-restricted disease in non-Jewish IBD patients and therefore identify HLA DRB1*0103 as a potentially important contributor to disease susceptibility and to expression of colonic involvement in IBD.
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PMID:A population- and family-based study of Canadian families reveals association of HLA DRB1*0103 with colonic involvement in inflammatory bowel disease. 1265 31

Genetic factors have a definitive role in the etiology of ulcerative colitis (UC). The mode of inheritance suggests a polygenic disease with the penetrance of the genetic factors being strongly influenced by environmental factors. Several studies have been reported associations between UC and the polymorphism of genes that are located in the major histocompatibility complex (MHC) on the short arm of chromosome 6. The human leukocyte antigen (HLA) class II genes are candidates for a role in the pathogenesis of UC, because their products play a central role in the immune response. The MHC region contains numerous immune related genes, and it has now become clear that different alleles of the MHC genes are strongly linked. Association studies have suggested a role for HLA-DR alleles in disease susceptibility to UC. Thus, HLA-DRB1*0103, DRB1*1502 and DRB1*12 were found to be positively associated with UC. On the other hand, the tumor necrosis factor alpha (TNF-alpha) gene encodes a proinflammatory cytokine that is found in increased concentrations in the mucosa of patients with inflammatory bowel disease. The regulation of TNF expression is in part genetically determined because the polymorphisms -238, -308, -863, -857, and -1031 found in the promoter region are associated with increased TNF production. Recent data suggests that TNF polymorphism may be more important in determining susceptibility to UC and these TNF markers could predict response to infusion with chimeric anti-TNF antibody.
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PMID:[Immunogenetics of chronic ulcerative colitis]. 1501 40

Spondyloarthritis tends to cluster in families and, to a great extent, is associated with human leukocyte antigen (HLA) B27. In fact, the population frequency of spondyloarthritis in most groups is proportional to that of HLA-B27. But the frequency of HLA-B27 in the population-at-large far exceeds that of spondyloarthritis, suggesting other genetic factors also are operative. Other major histocompatibility complex genes have been implicated, especially HLA-DR, though linkage to HLA-B27 confounds the analysis of this in many studies. Genome-wide scans have implicated regions on chromosomes 2q, 6p, 6q, 10q, 11q, 16q, 17q, and 19q in ankylosing spondylitis, on 4, 6p, and 17q in psoriasis, and on 7q and 16q in inflammatory bowel disease. The search for non-major histocompatibility complex candidate genes has been complicated by inadequate power, because of the small effect they exert on overall disease susceptibility, although recent studies are revealing promising candidates that must be confirmed by other groups.
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PMID:The genetic basis of spondyloarthritis. 1501 42

In addition to being involved in nutrient uptake, the epithelial mucosa constitute the first line of defense against microbial pathogens. A direct consequence of this physiological function is a very complex network of immunological interactions that lead to a strong control of the mucosal immune balance. The dysfunction of immunological tolerance is likely to be a cause of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD). HLA-G is a non-classical major histocompatibility complex (HLA) class I molecule, which is highly expressed by human cytotrophoblast cells. These cells play a role in immune tolerance by protecting trophoblasts from being killed by uterine NK cells. Because of the deregulation of immune system activity in IBD, as well as the immunoregulatory role of HLA-G, we have analyzed the expression of HLA-G in intestinal biopsies of patients with UC and CD. Our study shows that the differential expression of HLA-G provides a potential way to distinguish between UC and CD. Although the reason for this differential expression is unclear, it might involve a different mechanism of immune regulation. In addition, we demonstrate that in the lamina propria of the colon of patients with UC, IL-10 is strongly expressed. In conclusion, the presence of HLA-G on the surface of intestinal epithelial cell in patients with UC lends support to the notion that this molecule may serve as a regulator of mucosal immune responses to antigens of undefined origin. Thus, this different pattern of HLA-G expression may help to differentiate between the immunopathogenesis of CD and UC.
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PMID:Expression of HLA-G in inflammatory bowel disease provides a potential way to distinguish between ulcerative colitis and Crohn's disease. 1503 88

The aim of this study was to characterize the phenotype of leukocytes infiltrating the duodenal mucosa of cats with inflammatory bowel disease (IBD) by using immunohistochemistry and computer-aided morphometry to assess whether immunologic markers would aid in characterization of IBD. Frozen and formalin-fixed duodenal biopsies were collected from cats referred for investigation of chronic vomiting, diarrhea, or both (n = 34). Reference ranges were previously established by using duodenal samples from healthy cats (n = 16). No significant difference was found in the number of immunoglobulin G+ (IgG+) or IgA+ in either the villous lamina propria or the crypt lamina propria between cats with IBD and control cats. T cells (CD3+) increased in number from crypt to the tip of the villi in biopsies from both diseased (mean +/- SD for each group was 18.8 +/- 6.6 and 17.7 +/- 4.2 cells/ 10,000 m2 in cryptal areas to 25.2 +/- 9.5 and 29.1 +/- 13.3 cells/10,000m2 in villous areas) and healthy animals (17.9 +/- 3.9 cells/10,000 microm2 in cryptal areas to 24.1 +/- 9.3 cells/10,000 microm2 in villous areas) and no significant difference was found between diseased and control cats. By contrast, major histocompatibility complex (MHC) class II expression by leukocytes with dendritic cell or macrophage morphology in the lamina propria was significantly greater in cats with IBD (13.3 +/- 4.2 cells/10,000 microm2 in cryptal area; P = .016) than in healthy cats (11.9 +/- 3.0 cells/10,000 microm2) and MHC class II expression by enterocytes also was more pronounced in these cats showing an overall intensity of expression of 7.1 +/- 4.0 cells/10,000 microm2 in cats with IBD as opposed to 0.0 +/- 0.0 cells/10,000 microm2 to 0.3 +/- 0.7 cells/10,000 microm2 in healthy cats. These findings suggest that a subtle immunologic dysregulation occurs in spontaneously arising feline IBD.
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PMID:Immune cell populations in the duodenal mucosa of cats with inflammatory bowel disease. 1563 64

Although T-cell clones bearing T-cell receptors with high affinity for self-peptide major histocompatibility complex (MHC) products are generally eliminated in the thymus (recessive tolerance), the peripheral T-cell repertoire remains strongly biased toward self-peptide MHC complexes and includes autoreactive T cells. A search for peripheral T cells that might exert dominant inhibitory effects on autoreactivity has implicated a subpopulation of CD4(+)CD25(+) T cells called regulatory T cells (Tregs). Here, we discuss the role of cytokines and costimulatory molecules in the generation, maintenance, and function of Tregs. We also summarize evidence for the involvement of Tregs in controlling autoimmune diseases, including type 1 diabetes, experimental autoimmune encephalomyelitis, and inflammatory bowel disease. Last, we discuss our recent definition of the potential role of B7 expressed on activated T-effector cells as a target molecule for Treg-dependent suppression. These observations suggest that the engagement of B7 on effector T cells transmits an inhibitory signal that blocks or attenuates effector T-cell function. We restrict our comments to the suppression mediated by cells within the CD4 lineage; the impact of the cells within the CD8 lineage that may suppress via engagement of Qa-1 on effector T cells is not addressed in this review.
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PMID:Regulatory T cells and autoimmune disease. 1579 Mar 60

Ankylosing spondylitis (AS) is strongly associated with the major histocompatibility complex (MHC) class I antigen HLA-B27. This may have influence on the physiologic immune response. Whether it leads to an increased prevalence of infections and/or allergy in AS patients is unclear. This study aims to determine the prevalence of infections and allergic symptoms in patients with AS and to detect a possible association with clinical symptoms. Data on 1,080 AS patients and on 102 disc prolapse patients were collected by questionnaire. The proportion of patients with a symptomatic infection in the last year was 65.5% in AS patients in comparison with 25.5% in disc prolapse patients (p=0.0001). AS patients reported more gastrointestinal (GI) [odds ratio (OR) 5.07, 95% confidence interval (CI) 2.20-11.71], urinary tract (OR 2.81, 95%CI 1.41-5.72), and respiratory (OR 5.83, 95%CI 3.38-10.08) infections than did disc prolapse patients. Multiple infections were more common in AS patients across all infection types. Allergic symptoms were reported by AS patients more frequently than by disc prolapse patients (OR 5.13, 95%CI 3.49-8.80). Patients reporting concurrent inflammatory bowel disease were more likely to report GI (OR 3.0, 95%CI 1.9-4.8) and urinary tract (OR 1.7, 95%CI 1-2.8) infection than primary AS patients. In AS patients, infection was independently associated with female gender (OR 1.96, 95%CI 1.47-2.56), a history of significant peripheral joint inflammation (OR 1.55, 95%CI 1.18-2.05), and increasing pain duration (p=0.05). A high prevalence of common infections and allergic symptoms is seen in patients with AS, most of which are HLA-B27-positive. This may have implications both for underlying mechanisms of disease and for therapeutic options.
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PMID:The high prevalence of infections and allergic symptoms in patients with ankylosing spondylitis is associated with clinical symptoms. 1637 75

Inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory autoimmune conditions of the gastrointestinal tract. Other organs, such as the eyes, skin and articulations, are often affected and IBD may be accompanied by other diseases of autoimmune origin. There is no single etiological factor responsible for the onset of IBD. Recent advances in genetics and in the molecular mechanisms of the proteins coded by these genes have given rise to a new vision in understanding these complex diseases. Activation of specific genes that affect antigen presentation and the handling of cells by innate immunity may lead to autoimmunity with the consequent activation of the major histocompatibility complex (MHC) and multiple cytokines involved in the regulation of acquired immunity. In this review IBD is described as a constellation of diseases that can best be classified as barrier diseases. This vision, developed by Kiel in Germany, includes the idea that changes in our environment due to the westernization of civilization have not been met with adaptation of the innate immune system, and this has given rise to autoimmune diseases. These diseases affect 1-5 of 1000 individuals and represent a major burden on the national health systems of many countries on different continents. On a world scale, a major challenge is to generate interventions to prevent the development of these diseases in Asia, Latin America and Africa.
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PMID:Contribution of genetics to a new vision in the understanding of inflammatory bowel disease. 1693 58


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