Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The idea that opioids modulate the immune system is not new. By the late 19th century, Cantacuzene, used morphine to suppress cellular immunity and lower the resistance of guinea pigs to bacterial infection. While exogenous opioids mediate immunosuppression, endogenous opiates exert opposite actions. Acute and chronic opioid administration is known to have inhibitory effects on humoral and cellular immune responses including antibody production, natural killer cell activity, cytokine expression, and phagocytic activity. Opiates behave like cytokines, modulating the immune response by interaction with their receptors in the central nervous system and in the periphery. Potential mechanisms by which central opiates modulate peripheral immune functions may involve both the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. The presence of opioid receptors outside the central nervous system is increasingly recognized. Those receptors have been identified not only in peripheral nerves but also in immune inflammatory cells. The immunosuppression mediated by opiates may explain the increased incidence of infection in heroin addicts. Opiates may also promote immunodeficiency virus infection by decreasing the secretion of alpha and beta chemokines (important inhibitory cytokines for the expression of HIV) and at the same time increasing the expression of chemoreceptors CCR5 and CCR3, coreceptors for the virus. The fact that peripheral immunosupression is mediated at least in part by opioid receptors located in the central nervous system and that intrathecally administered opioids do not exert the same immunosuppressive effects may have important clinical implications for those patients receiving long-term opioid therapy for malignant and nonmalignant pain.
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PMID:Opioid therapy and immunosuppression: a review. 1535 31

Data collection for the national registry for patients with primary immunodeficiency disorders in the Republic of Ireland commenced in 1996. One hundred and fifteen cases of primary immunodeficiency diseases were registered between December 1996 and February 2003. The most frequent primary immunodeficiency disorders were antibody deficiency (n = 53) and complement deficiency (n = 32). In addition, patients with T cell deficiency (n = 11) and chronic granulomatous disease (n = 11) were identified. A small number of patients with Wiskott-Aldrich syndrome, natural killer cell deficiency, DiGeorge syndrome and chronic mucocutaneous candidiasis were also registered. Comparison of our data with that recently reported in the European registry revealed that complement deficiency was more prevalent in the Republic of Ireland compared to other European countries. Results of our registry point to a significant prevalence of primary immunodeficiency disorders in the Republic of Ireland (2.9 cases per 100,000 population). However, it is likely that these figures underestimate the true prevalence of such cases in the country. We hope, with increased awareness of the national registry among primary care physicians, that more patients will be included and we will be able to identify accurately the frequency and the distribution of these disorders.
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PMID:Primary immunodeficiency disorders in the Republic of Ireland: first report of the national registry in children and adults. 1574 60

The effects of 2 weeks of refeeding by cyclic enteral nutrition on chronically malnourished (mean global nutritional deficiency 19.9 +/- 1.1%) hospitalized patients were assessed in a prospective study with special attention paid to immunological status. All patients were immunodeficient, with cell-mediated immunity being more affected than humoral immunity. After 2 weeks of refeeding, nutritional status had improved by 29.8%. Initially abnormal parameters of humoral immunity (IgM, C3 and C4) improved significantly (P < 0.05) between day 0 and day 15. The following cell-mediated immunity parameters also improved significantly (P < 0.05): CD8, monocyte count, natural killer cell activity and skin tests. Short-term refeeding by cyclic enteral nutrition appears to be a safe and effective way of improving immunodeficiency in chronically malnourished patients, with predictable consequences on infection.
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PMID:Effects of cyclic enteral nutrition on the immunological status of malnourished patients. 1684 33

Artemis gene mutations are responsible for the development of a severe combined immunodeficiency [radiation-sensitive (RS) SCID] characterized by a severe B and T cell deficiency and a normal natural killer cell population. To establish the feasibility of a gene therapy approach to the treatment of RS-SCID, we generated a series of lentiviral vectors expressing human Artemis from different promoters and used them to transduce highly purified hematopoietic stem cells (HSCs) from Artemis knockout mice. HSCs transduced by the different viruses were transplanted into either lethally irradiated Rag-1-deficient animals or Artemis knockout mice treated with a nonmyeloablative dose of Busulfan. In both models, transplantation of HSCs transduced by a vector that used a murine phosphoglycerate kinase (PGK) promoter led to a complete functional correction of the immunodeficiency. Corrected animals displayed rescue of mature B cells with normal levels of serum immunoglobulins, together with complete rescue of the T cell compartment as evidenced by the presence of mature T lymphocytes in peripheral blood as well as normal values of thymocytes in thymus. Those B and T cells were capable of activation, as shown both by in vitro stimulation responses and in vivo after immune challenge. Overall, the results indicate that a gene therapy approach for RS-SCID involving the transplantation of genetically modified HSCs is indeed feasible. Furthermore, our studies suggest the possibility that nonmyeloablative conditioning regimens might be effectively used to promote engraftment of genetically modified cells in the case of diseases where standard irradiation-based myeloablative bone marrow transplantation protocols may prove problematic.
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PMID:Complete correction of murine Artemis immunodeficiency by lentiviral vector-mediated gene transfer. 1706 50

The pathogenicity of the primate lentiviruses, human, and simian immunodeficiency viruses, is host-specific. Previous studies indicated that the highly pathogenic human lentivirus HIV-1 has markedly reduced pathogenicity compared to the pathogenic simian lentivirus SIV in pigtail macaques (Macaca nemestrina). We therefore hypothesized that the pigtail macaque peripheral blood mononuclear cells (mPBMCs) would respond differently to infections of HIV-1 and pathogenic SIV. To elucidate the cellular responses to the infections of HIV-1 and SIV, we infected mPBMC with these two viruses. Like infections in vivo, HIV-1 and SIV demonstrated distinct replication kinetics in mPBMCs, with HIV-1 replicating at significantly lower levels. Similarly, gene expression profiling facilitated by macaque-specific oligonucleotide microarrays also revealed distinct expression patterns of genes between the HIV-1- and SIV-infected mPBMCs; in particular, genes associated with the antigen presentation, T cell receptor, ERK/MAPK signaling, Wnt/beta-catenin signaling, and natural killer cell signaling pathways were differentially regulated between these two viruses. Most interestingly, despite the lower levels of replication, HIV-1 triggered a more robust regulation of immune response genes early after infection; the converse was true in SIV-infected mPBMCs. Our results therefore suggest that macaques may be controlling the infection of HIV-1 at an early stage through coordinated regulation of host defense pathways.
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PMID:Functional genomics analyses of differential macaque peripheral blood mononuclear cell infections by human immunodeficiency virus-1 and simian immunodeficiency virus. 1750 74

Human immunodeficiency virus type 1 (HIV-1) Nef downregulates HLA-A and -B molecules, but not HLA-C or -E molecules, based on amino acid differences in their cytoplasmic domains to simultaneously evade cytotoxic T lymphocyte (CTL) and natural killer cell surveillance. Rhesus macaques and sooty mangabeys express orthologues of HLA-A, -B, and -E, but not HLA-C, and many of these molecules have unique amino acid differences in their cytoplasmic tails. We found that these differences also resulted in differential downregulation by primary simian immunodeficiency virus (SIV) SIV(smm/mac) and HIV-2 Nef alleles. Thus, selective major histocompatibility complex class I downregulation is a conserved mechanism of immune evasion for pathogenic SIV infection of rhesus macaques and nonpathogenic SIV infection of sooty mangabeys.
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PMID:Selective downregulation of rhesus macaque and sooty mangabey major histocompatibility complex class I molecules by Nef alleles of simian immunodeficiency virus and human immunodeficiency virus type 2. 1819 57

Hematopoietic SCT from a partially HLA-mismatched (HLA-haploidentical) first-degree relative offers the benefits of rapid and near universal donor availability but also the risks that result from traversing the HLA barrier; namely, graft failure, severe GVHD and prolonged immunodeficiency. Improvements over the last 10 years in conditioning regimens, graft engineering and pharmacological immunoprophylaxis of GVHD have substantially reduced the morbidity and mortality of HLA-haploidentical SCT. Highly immunosuppressive but nonmyeloablative conditioning extends the availability of HLA-haploidentical SCT to elderly hematologic malignancy patients lacking HLA-matched donors and permits recovery of autologous hematopoiesis in the event of graft failure. Current regimens for HLA-haploidentical SCT are associated with a 2-year non-relapse mortality of 20+/-5%, relapse of 35+/-15% and overall survival of 50+/-20%. Major developmental areas include harnessing natural killer cell alloreactivity to reduce the risk of disease relapse and improving immune reconstitution by delayed infusions of lymphocytes selectively depleted of alloreactive cells. Hematologic malignancy patients who lack suitably matched related or unrelated donors can now be treated with HLA-haploidentical related donor or unrelated umbilical cord blood SCT. Future clinical trials will assess the relative risks and benefits of these two graft sources.
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PMID:Hematopoietic SCT from partially HLA-mismatched (HLA-haploidentical) related donors. 1867 75

Familial hemophagocytic lymphohistiocytosis is a rare disorder characterized by lethal primary immunodeficiency associated with hypercytokinemia and a concomitant defect in natural killer cell cytotoxicity. We report a fatal case of familial hemophagocytic lymphohistiocytosis homozygous caused by a novel nonsense mutation of the perforin gene. Homozygosity was established to be the result of uniparental disomy of the maternal chromosome 10. Uniparental disomy increases the risk of autosomal recessive disease.
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PMID:Novel mutation of the perforin gene and maternal uniparental disomy 10 in a patient with familial hemophagocytic lymphohistiocytosis. 1879 42

Cryptococcosis caused by Cryptococcus neoformans has a wide range of clinical presentations, varying from asymptomatic colonization of the respiratory airways to the dissemination of infection into different parts of body. It is more common among immunosupressed patients such as human immunodeficiency virus (HIV) positive ones. In this report we present a case with C. neoformans meningitis and miliary pulmonary infiltrates suggesting pulmonary tuberculosis without HIV infection. A-70-years-old male was admitted to the hospital with mental confusion, 3-weeks history of headache, weight loss, dry cough and fatigue. Physical examination was normal except neck stiffness. Cerebrospinal fluid (CSF) white cell count was 120/mm3 (80% polimorphonuclear cells). Gram staining of CSF revealed poorly stained gram-positive yeast cells. Empirical therapy with lipozomal amphotericin B, ceftriaxone and ampicillin combination was started. When C. neoformans growth was detected on CSF culture, ceftriaxone and ampicillin were discontinued. Patient became conscious at 24th hour of the treatment. Peripheric blood flow-cytometric analysis revealed a significant decrease in absolute CD4+ T lymphocytes, and in CD8+28+ T lymphocytes in addition a significant increase in natural killer cell ratio. Blood immunoglobulin and complement levels were found normal. Cranial magnetic resonance imaging and computerized tomogralphy (CT) of the abdomen were normal, however, chest CT revealed multiple parenchymal millimetric nodular infiltrations on both sides and minimal fibrotic alterations. Acid-fast staining of CSF, tuberculosis culture, tuberculosis PCR results and repeated HIV serology were found negative. Despite the lack of microbiological confirmation, empirical antituberculosis treatment was also started with the suspicion of miliary tuberculosis as the patient had a symptom of long-term dry cough, miliary infiltrations on chest CT, anergic tuberculin skin test and a history of pulmonary tuberculosis in childhood. After two weeks, amphotericin B was changed to oral fluconazole which was continued for an additional eight weeks. Antituberculosis therapy was given for nine months. Control chest CT taken after four months of antituberculosis therapy revealed improvement of the lesions. This presentation emphasizes the fact that cryptococcal infections may develop in HIV negative patients, even together with tuberculosis in certain cases and radiological findings of the two infections may be confusing when both of them invade the lungs.
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PMID:[Cryptococcus neoformans meningitis in a HIV negative miliary tuberculosis-suspected patient]. 1882 99

The loss of the CD16a, Fc receptor for IgG type III, (FcgammaRIIIa) B73.1/Leu11c binding epitope, detected by the monoclonal antibody (mAb) used in routine enumeration of NK cells or monocytes, has been observed in children with recurrent viral infections. It has also been linked with the change of leucine (L) to histidine (H) or arginine (R) at amino acid position 48 (FcgammaRIIIa-48L/R/H) in the CD16a receptor. The reactivity of the anti-CD16a clone B73.1/Leu11c mAb with monocytes and NK cells was examined in patients with primary immunodeficiencies (n=167), gastrointestinal malignancies (n=91) and healthy subjects (n=88). Cells of only 12 children, 11 with diagnosed primary immunodeficiency and one with recurrent bacterial infections were not reactive with B73.1/Leu11c mAb. In contrast to previous findings, no linkage between the loss of B73.1/Leu11c binding epitope and herpes virus infections was observed. Furthermore, the sequence analysis of the FcgammaRIIIa gene performed in these 12 patients and 11 healthy subjects revealed that all of them had FcgammaRIIIa-48L/L genotype. Thus, the loss of B73.1/Leu11c binding epitope was not associated with the FcgammaRIIIa-48 polymorphism. The commonly described FcgammaRIIIa-158 polymorphism was determined to be 158V/V in 11 patients and 5 healthy subjects. Moreover, no linkage between FcgammaRIIIa-48L/L and -158F/F genotypes was observed. It is suggested that the loss of the B73.1/Leu11c binding epitope is connected with primary immunodeficiency disorders, but not associated with the FcgammaRIIIa-48 polymorphism.
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PMID:The loss of the CD16 B73.1/Leu11c epitope occurring in some primary immunodeficiency diseases is not associated with the FcgammaRIIIa-48L/R/H polymorphism. 2066 61


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