Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021831 (enteropathy)
 4,403 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX, OMIM 304790) is a rare, recessive disorder resulting in aggressive autoimmunity and early death. Mutations in FOXP3 have been identified in 13 of 14 patients tested. Research in the mouse model, scurfy, suggests that autoimmunity may stem from a lack of working regulatory T cells. We review published reports regarding the genetics, clinical features, immunology, pathology, and treatment of IPEX. We also report three new patients who were treated with long term immunosuppression, followed by bone marrow transplantation in two. IPEX can be differentiated from other genetic immune disorders by its genetics, clinical presentation, characteristic pattern of pathology, and, except for high IgE, absence of substantial laboratory evidence of immunodeficiency. While chronic treatment with immunosuppressive drugs may provide temporary benefit for some patients, it does not cause complete remission. Remission has been observed with bone marrow transplantation despite incomplete engraftment, but the long term outcome is uncertain.
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PMID:Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. 1216 90

A small proportion of coeliac disease (CD) patients fail to improve after a gluten-free diet (GFD) and may be considered as atypical regarding their outcome (refractory coeliac disease). The aim of this study is to diagnose and manage patients with CD who fail to improve after a GFD. Refractory coeliac disease (RCD) is a malabsorption syndrome defined by persisting villous atrophy with, usually, an increase of intraepithelial lymphocytes (IELs) in the small bowel in spite of a strict GFD and comprises a heterogenous group of diseases. Some of these diseases have to be excluded and can be treated by specific therapies like antibiotics in tropical sprue and giardiasis and immune globulin substitution in common variable immunodeficiency, while other malabsorption syndromes are less well defined and may require immunosuppressive therapy. Standardized treatment, however, has not been evaluated in such patients so far. In a subgroup of patients with RCD, an abnormal intraepithelial lymphocyte (IEL) population may be observed with the lack of surface expression of usual T-cell markers (CD3-CD8 and/or the T-cell receptor (TCR)) on IELs associated with T-cell clonality pattern suggest the presence of an early enteropathy-associated T-cell lymphoma (EATL) in a subgroup of patients with RCD. This hypothesis has been supported by studies, which revealed progression into overt intestinal T-cell lymphomas in a subgroup of RCD. Steroid treatment has been reported effective even in patients with underlying early EATL. However, long-term results are unsatisfactory in most of these patients with RCD and parenteral nutrition has to be applied in some of these cases. First results with more aggressive chemotherapies and use of cytokines are under way. Due to the difficulty of diagnostic and therapeutic regimens patients should be referred to tertiary centres for coeliac disease.
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PMID:Refractory coeliac disease. 1592 46

Far from being mutually exclusive, immunodeficiency and autoimmunity may occur simultaneously. During the last years, analysis of Autoimmune Polyendocrinopathy--Candidiasis--Ectodermal Dystrophy (APECED) and Immunodysregulation--Polyendocrinopathy--Enteropathy--X-linked (IPEX), two rare monogenic forms of immunodeficiency associated with autoimmunity, has led to the identification of Auto Immune Regulator (AIRE) and Forkhead Box P3 (FOXP3), essential transcriptional regulators, involved in central tolerance and peripheral immune homeostasis, respectively. Characterization of the molecular and cellular mechanisms involved in APECED, and recognition that AIRE expression is sustained by effective thymopoiesis, has recently allowed to define that the autoimmunity of Omenn syndrome, a combined immunodeficiency due to defects of V(D)J recombination, also results from defective expression of AIRE. The implications of identification of the basis of autoimmunity in these rare forms of immunodeficiency have important implications for a better understanding of more common autoimmune disorders, and for development of novel therapeutic approaches.
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PMID:Immunodeficiencies with autoimmune consequences. 1668 78

Diarrhoea and malnutrition are common findings in patients with the Acquired Immune Deficiency Syndrome (AIDS). In this disease, enteropathy leads to fat and D-xylose malabsorption and chronic non-specific inflammation of the small bowel. Moreover, gastrointestinal infection can induce severe diarrhoea. Depletion in real body cell mass, body fat content, and weight loss have been observed. Nutritional therapy is mandatory when weight loss is 10% or greater. Enteral feeding is not easily achieved. Parenteral feeding including fat as a nonprotein calorie source improves general condition. The use of intravenous fat emulsions has been hypothesized to have several beneficial effects. Fluidisation of human immunodeficiency virus membranes by lipid emulsions through cholesterol extraction could decrease the infectivity of the virus. Long term intravenous nutrition may be more than a treatment for malabsorption and depletion; it may possibly have direct pharmacological effects.
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PMID:Nutrition, the gastrointestinal tract and the acquired immune deficiency syndrome. Facts and perspectives. 1683 3

We show that at least half of patients with common variable immunodeficiency (CVID) have circulating CD8(+) T cells specific for epitopes derived from cytomegalovirus (CMV) and/or the Epstein-Barr virus (EBV). Compared to healthy age-matched subjects, more CD8(+) T cells in CVID patients were committed to CMV. Despite previous reports of defects in antigen presentation and cellular immunity in CVID, specific CD4(+) and CD8(+) T cells produced interferon (IFN)-gamma after stimulation with CMV peptides, and peripheral blood mononuclear cells secreted perforin in response to these antigens. In CVID patients we found an association between a high percentage of circulating CD8(+) CD57(+) T cells containing perforin, CMV infection and a low CD4/CD8 ratio, suggesting that CMV may have a major role in the T cell abnormalities described previously in this disease. We also show preliminary evidence that CMV contributes to the previously unexplained severe enteropathy that occurs in about 5% of patients.
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PMID:The T cell response to persistent herpes virus infections in common variable immunodeficiency. 1703 75

Diarrheal disease is a major cause of childhood morbidity and mortality worldwide. Chronic enteropathy with subsequent persistent diarrhea and associated vicious cycles of malnutrition, increased gut permeability and secondary immunodeficiency are particularly devastating in the childhood population. The major causes of chronic enteropathy differ significantly between developed countries and developing countries. In developed countries, infectious and postinfectious diarrhea as well as abnormalities in immune response including celiac disease, food-induced allergic enteropathy and idiopathic inflammatory bowel disease account for most cases of chronic enteropathy. In developing countries, syndromic persistent diarrhea associated with malnutrition and secondary immunodeficiency due to human immunodeficiency virus (HIV) infection predominate as the major causes of chronic enteropathy. These latter two causes account for a disproportionate share of the more than 2.5 million deaths of children under 5 years of age due to diarrhea each year worldwide. From a practical perspective, diagnostic evaluation of chronic enteropathy in developing countries is often limited to identifying potential causative enteropathogens and antimicrobial treatment. Proper management with an emphasis on fluid homeostasis and protocolized nutritional therapy and rehabilitation is essential to successful treatment of syndromic persistent diarrhea.
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PMID:Chronic enteropathy: clinical aspects. 1724 93

Simian immunodeficiency virus (SIV) infection of macaques and human immunodeficiency virus type 1 (HIV-1) infection of humans result in variable but generally fatal disease outcomes. Most SIV-infected macaques progress to AIDS over a period of 1 to 3 years, in the face of robust SIV-specific immune responses (conventional progressors [CP]). A small number of SIV-inoculated macaques mount transient immune responses and progress rapidly to AIDS (rapid progressors [RP]). We speculated that the underlying pathogenic mechanisms may differ between RP and CP macaques. We compared the pathological lesions, virus loads, and distribution of virus and target cells in SIVsmE660- or SIVsmE543-infected RP and CP rhesus macaques at terminal disease. RP macaques developed a wasting syndrome characterized by severe SIV enteropathy in the absence of opportunistic infections. In contrast, opportunistic infections were commonly observed in CP macaques. RP and CP macaques showed distinct patterns of CD4(+) T-cell depletion, with a selective loss of memory cells in RP macaques and a generalized (naive and memory) CD4 depletion in CP macaques. In situ hybridization demonstrated higher levels of virus expression in lymphoid tissues (P < 0.001) of RP macaques and a broader distribution to include many nonlymphoid tissues. Finally, SIV was preferentially expressed in macrophages in RP macaques whereas the primary target cells in CP macaques were T lymphocytes at end stage disease. These data suggest distinct pathogenic mechanisms leading to the deaths of these two groups of animals, with CP macaques being more representative of HIV-induced AIDS in humans.
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PMID:Unique pathology in simian immunodeficiency virus-infected rapid progressor macaques is consistent with a pathogenesis distinct from that of classical AIDS. 1737 1

Gastrointestinal (GI) disease is a debilitating feature of human immunodeficiency virus (HIV) infection that can occur in the absence of histopathological abnormalities or identifiable enteropathogens. However, the mechanisms of GI dysfunction are poorly understood. The present study was undertaken to characterize changes in resident and inflammatory cells in the enteric nervous system (ENS) of macaques during the acute stage of simian immunodeficiency virus (SIV) infection to gain insight into potential pathogenic mechanisms of GI disease. Ganglia from duodenum, ileum, and colon were examined in healthy and acutely infected macaques by using a combination of routine histology, double-label immunofluorescence and in situ hybridization. Evaluation of tissues from infected macaques showed progressive infiltration of myenteric ganglia by CD3+ T cells and IBA1+ macrophages beginning as early as 8 days postinfection. Quantitative image analysis revealed that the severity of myenteric ganglionitis increased with time after SIV infection and, in general, was more severe in ganglia from the small intestine than in ganglia from the colon. Despite an abundance of inflammatory cells in myenteric ganglia during acute infection, the ENS was not a target for virus infection. This study provides evidence that the ENS may be playing a role in the pathogenesis of GI disease and enteropathy in HIV-infected people.
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PMID:Enteric ganglionitis in rhesus macaques infected with simian immunodeficiency virus. 1739 57

FoxP3 determines the development of CD4+CD25+ regulatory T (Treg) cells and represses interleukin-2 (IL-2) expression in Treg cells. However, human immunodeficiency virus type 1 (HIV-1) infects and replicates efficiently in FoxP3+ Treg cells. We report that, while inhibiting IL-2 gene expression, FoxP3 enhances gene expression from HIV-1 long terminal repeat (LTR). This FoxP3 activity requires both the N- and C-terminal domains and is inactivated by human IPEX (immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome) mutations. FoxP3 enhances HIV-1 LTR via its specific NFkappaB binding sequences in an NFkappaB-dependent fashion in T cells but not in HEK293 cells. FoxP3 decreases level of histone acetylation at the interleukin-2 locus but not at the HIV-1 LTR. Although NFkappaB nuclear translocation is not altered, FoxP3 enhances NFkappaB-p65 binding to HIV-1 LTR. These data suggest that FoxP3 modulates gene expression in a promoter sequence-dependent fashion by modulating chromatin structure and NFkappaB activity. HIV-1 LTR has evolved to both highjack the T-cell activation pathway for expression and to resist FoxP3-mediated suppression of T-cell activation.
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PMID:FoxP3 enhances HIV-1 gene expression by modulating NFkappaB occupancy at the long terminal repeat in human T cells. 1741 86

The paper describes the results of studying the immune status of 1,960 patients with stomach, pancreas, liver, gall bladder, small and large intestine disorders, who were treated in the Central Research Institute of Gastroenterology. The results of the study demonstrate that alimentary system diseases are concomitant with changes in the functional activity of the immune system and development of the systemic immune response aimed at the neutralization and elimination of pathogenic agents. Impaired regulatory and efferent lymphocyte capacities, increased synthesis of cytokines, immunoglobulins, heterologous (anti-viral, anti-bacterial or antigliadin), autologous (to parietal cells, microsome mitochondria, tissue transglutaminase) antibodies, formation of immune complexes, autoimmune reactions and secondary immunodeficiency are specific immune mechanisms of the pathological process development, its synchronization and progression in patients with alimentary system diseases. Changes in the immunological status indices are expressed in varying degree depending on the organ involved, etiological factor, clinical course and stage of the disease, as well as treatment used. The immunological status indices have maximal values in cases of chronic hepatitis, hepatic cirrhosis, peptic or duodenal ulcer, cholelithiasis, chronic pancreatitis, gluten-sensitive enteropathy and minimal values in cases of chronic gastritis, gastroesophageal disease, steatohepatitis and irritable bowel syndrome. These data are sufficient for developing an algorithm of immune diagnostics for a number of alimentary system diseases. The study of immune status indices is of great diagnostic and prognostic value as it defines the etiological factor, intensity of inflammatory, infectious and autoimmune processes as well as disease stage and activity, its forecast and the efficacy of treatment of alimentary system diseases.
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PMID:[Diagnostic and prognostic value of humoral immune status indices for alimentary system diseases]. 1753 52


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