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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Common variable immunodeficiency (CVID) is the second most prevalent primary immunodeficiency disorder but clinically the most important. It causes a wide spectrum of symptoms and signs affecting many systems of the body. CVID is a combination of humoral and cell-mediated deficiency, which explains not only why so many systems are affected but also why standard therapy in the form of intravenous immunoglobulin is not always effective. The gastrointestinal tract is the largest immune organ in the body, and it is therefore expected that this immunodeficiency will affect it in some way. The gastrointestinal manifestations of CVID are variable and tend to mimic known diseases, such as celiac sprue, pernicious anemia, and inflammatory bowel disease, but show significant differences on the microscopic level. Many studies continue to confirm a high prevalence of inflammatory, malignant, and infectious gastrointestinal disorders in patients with CVID. The T-cell-mediated defects of this immunodeficiency disorder are thought to be the cause of the majority of the gastrointestinal disorders in CVID and not the antibody deficiency. Therefore, intravenous immunoglobulin alone may be ineffective. Combination therapy with immunomodulators, such as azathioprine and 6-mercaptopurine, may be needed to treat these gastrointestinal manifestations of CVID.
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PMID:Common variable immunodeficiency and the gastrointestinal tract. 1534 13

Immune thrombocytopenic purpura (ITP), alone or in combination with autoimmune hemolytic anemia (Evans syndrome) and/or autoimmune neutropenia, is frequent in patients with common variable immunodeficiency (CVID). A 34-year-old man with CVID had long-standing unresponsive ITP. The patient had a 9-year history of CVID on substitutive therapy with intravenous immunoglobulin (IVIG). The clinical course of CVID was complicated with refractory fistulizing inflammatory bowel disease, nodular regenerative hyperplasia of the liver, splenomegaly, severe portal hypertension, and hypercatabolism of IgG. ITP was refractory to medical therapy, including different combinations of corticosteroids, high-dose IVIG, azathioprine, and vincristine. Splenectomy was not performed because of severe portal hypertension. He received a total five doses of rituximab, a monoclonal antibody directed against CD20 antigen, at a dose of 375 mg/m(2). After an initially slow response, his platelet count increased to more than 50,000/microL by the fourth week of infusion. Therapy was well tolerated, and B lymphocytes were effectively depleted from the peripheral blood. The patient was completely tapered off glucocorticoids and maintained platelets at above 40,000/microL. The patient has not taken immunosuppressive agents for 11 months. Early treatment with rituximab might be an option for patients with CVID and ITP that do not respond to other treatments or for patients for whom a splenectomy is contraindicated.
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PMID:Partial response to anti-CD20 monoclonal antibody treatment of severe immune thrombocytopenic purpura in a patient with common variable immunodeficiency. 1612 7

We report on a family with three stillborn males, three affected males who were small for gestational age and died within 8 months, and one male who died at age 5 years. This boy had cone-shaped teeth and oligoodontia. He had serious bacterial infections and inflammatory bowel disease. Mutations in the NF-kappaB essential modulator (NEMO) gene have recently been shown to be the cause of a group of ectodermal dysplasia and immunodeficiency disorders (EDA-ID). Analysis of the NEMO gene revealed a nucleotide change in the consensus sequence of the splicing donor site of exon 6 IVS6 + 5G --> A(1027 + 5G --> A), which has not previously been described in EDA-ID. RT-PCR analysis of fibroblast RNA from an aborted affected male fetus demonstrated a skipping of exons 4, 5, and 6 which resulted in a truncated protein of about 35 kDa revealed by NEMO antibody. The skipping of exons 4, 5, and 6 did not affect the ORF of the C-terminal of NEMO encoded by exons 7, 8, 9, and 10, which contains a coiled-coil motif (CC2), a leucin-zipper (LZ), and a zinc finger motif (ZF) sub-domains of NEMO. IkappaBalpha degradation was strongly impaired in the fetal fibroblasts, suggesting an impaired NF-kappaB signaling. One healthy carrier had a completely skewed X-inactivation pattern with the normal X active, whereas the two other carriers had a random X-inactivation pattern. This family may represent a new phenotype within the EDA-ID disorders. From the heterogeneity in X-inactivation phenotype, we conclude that this mutation is not deleterious enough to be lethal for peripheral blood cells.
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PMID:Novel splicing mutation in the NEMO (IKK-gamma) gene with severe immunodeficiency and heterogeneity of X-chromosome inactivation. 1633 36

Common variable immunodeficiency (CVID) is the commonest primary immunodeficiency disease characterized by defective antibody production and various degrees of T cell numbers abnormality or impaired proliferation to mitogens. Clinical features include recurrent bacterial sinopulmonary and gastrointestinal infections. Autoimmunity is very common in CVID, occurring in approximately 25% of the patients particularly with autoimmune thrombocytopenia, hemolytic anemia, inflammatory bowel disease, and rheumatoid arthritis. Persistent antigen stimulation, secondary to a defective eradication of pathogens followed by a compensatory exaggerated chronic inflammatory response, is the primary cause leading to autoimmunity. Here we describe a girl with CVID in whom a chronic liver disease mimicking autoimmune hepatitis developed after hepatitis C virus infection. The immunosuppressive treatment with cyclosporine A proved effective in reversing liver disease.
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PMID:Successful treatment with cyclosporine A of HCV-driven chronic liver disease mimicking autoimmune hepatitis in a patient with common variable immunodeficiency. 1643 75

Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by various degrees of hypogammaglobulinemia. Similar to many immunodeficiency disorders, autoimmunity is common with an association with autoimmune cytopenias, a sarcoidosis-like disorder and inflammatory bowel disease. Recent efforts have characterized selective immunological defects and genetic associations in CVID and demonstrate an increased tendency towards loss of tolerance. The mainstay of treatment of autoimmune disease in such patients is often high dose IVIG and corticosteroids, although other therapies, including TNF-alpha antagonists, have been reported. While the etiology of increased autoimmunity in CVID remains elusive, certain genetic predispositions in combination with repeated antigen exposure and overall immune dysregulation inherent in CVID likely play a significant role.
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PMID:Common variable immune deficiency and autoimmunity. 1692 May 73

Helminthic infections occur worldwide, especially in developing countries. About one-quarter of the world's population, 1.5 billion, are infected with one or more of the major soil-transmitted helminths, including hookworms, ascarids, and whipworms. Schistosomes infect more than 200 million people worldwide with 600 million at risk in 74 countries. The interaction between helminths and the host's immune system provokes particular immunomodulatory and immunoregulatory mechanisms that ensure their survival in the host for years. However, these changes might impair the immunological response to bystander bacterial, viral, and protozoal pathogens and to vaccination. Modulation of the immune system by infection with helminthic parasites is proposed to reduce the levels of allergic responses and to protect against inflammatory bowel disease. In this review, we summarize the immunological milieu associated with helminthic infections and its impact on viral infections, mainly hepatitis B virus, hepatitis C virus, and human immunodeficiency virus in humans and experimental animals.
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PMID:Immune modulation by helminthic infections: worms and viral infections. 1696 84

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

We have analysed data from 150 patients initially classified as having CVID. About 10% had laboratory abnormalities suggesting known single gene disorders (eg: hyper-IgM syndrome), and in a few a genetic defect has been confirmed. We have attempted to sub-classify the remaining patients by analysis of their circulating lymphocytes. B lymphocyte markers have been used to estimate the numbers of circulating immature and class switched B cells; there is an association between the presence of high relative numbers of immature circulating B cells, splenomegaly and autoimmune disease. About 25% of CVID patients have a moderate CD4+ T lymphopenia, sometimes with a relative expansion of CD8+ T cells. About 30% of CVID patients have persistent relatively high levels of circulating CD8+ T cells binding immunogenic peptides from EBV or CMV. Many of these patients also have high relative numbers of circulating CD8+ perforin positive T cells, and there is evidence that these cells may be responsible for neutropenia or inflammatory bowel disease in some patients. The clinical spectrum of CVID is diverse, with some patients suffering from few infections, and over 50% have evidence of structural lung damage. About 25% of UK patients have chronic inflammation in various organs, particularly the lungs, liver and spleen, often with granulomatous changes. Steroids are used to treat many of the patients with chronic inflammatory complications, although trials are in progress with anti-TNF agents. The incidence of these inflammatory complications is different between countries, being rare in Sweden. Attempts to correlate clinical phenotypes with the laboratory abnormalities described above have been disappointing, suggesting that unknown genetic factors unrelated to the cause of the immunodeficiency determine the complications; attempts to identify some of these factors will be discussed. Finally a provisional scheme to sub classify CVID patients according to lymphocyte abnormalities will be presented, the purpose being to focus the screening of candidate genes causing CVID to specific subsets of patients.
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PMID:Clinical and Immunological Spectrum of Common Variable Immunodeficiency (CVID). 1730

The evaluation of patients with colitis of recent onset is a relatively common clinical challenge. The main considerations are infectious colitides, idiopathic IBD, ie, ulcerative and Crohn's colitis, and colonic ischemia. An initial risk assessment on the basis of such factors as concurrent symptoms in contacts, travel history, medications, and human immunodeficiency virus risk factors should be followed by a thorough clinical history, physical examination, stool studies, blood tests, and, in selected cases, endoscopic examination and serologic tests. Biopsies can be decisive in distinguishing among the different types of acute colitis and might help identify specific etiologies. The diagnostic yield of biopsies is maximized by appropriate sampling of the colonic mucosa and by sharing the clinical and endoscopic findings with the pathologist, eg, via a copy of the endoscopy report.
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PMID:Diagnosis of colitis: making the initial diagnosis. 1791 88

We present three common variable immunodeficiency (CVID) patients with severe inflammatory bowel disease of unknown aetiology, resistant to steroid treatment, treated with infliximab. After exclusion of any infection, infliximab was given at a dose of 5 mg/kg every 4 weeks for a 3 month induction followed by every 4-8 weeks depending on clinical response. Two of these patients had predominantly small bowel disease; they both showed clinical response to infliximab with weight gain and improvement of quality of life scores. The third patient had large bowel involvement with profuse watery diarrhea; this patient improved dramatically within 48 hours of having infliximab treatment. All three patients have been maintained on infliximab treatment for between 5 and 53 months (mean 37 months) with no evidence of increased susceptibility to infections in the patients with small bowel disease, although the third patient developed two urinary tract infections and a herpes zoster infection following therapy. This is the first small case series to show that infliximab is a useful addition to current therapy in this rare group of patients with potentially life threatening enteritis.
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PMID:Anti-tumour necrosis factor-alpha therapy for severe enteropathy in patients with common variable immunodeficiency (CVID). 1782 45


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