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)

Host defense mechanisms were evaluated in a 4-1/2-year-old boy with recurrent pyogenic infections and a unique hyperkeratotic skin disorder. The patient's neutrophils were consistently defective in chemotactic responsiveness but had normal NBT reduction, glucose oxidation, and iodination. Serum concentrations of IgE were markedly elevated and the secondary antibody response was abnormal. No T-cell dysfunction was detected. These findings suggest a relationship between this patient and patients with other syndromes associated with recurrent infections, cutaneous disease, defective chemotaxis, immunodeficiency, and hyperimmunoglobulinemia E.
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PMID:Defective neutrophil chemotaxis with variant ichthyosis, hyperimmunoglobulinemia E, and recurrent infections. 118 92

Progressive lymphoproliferation and increasingly severe immunodeficiency are prominent features of a syndrome, designated mouse AIDS, which develops in susceptible strains of mice infected with the mixture of murine leukemia viruses, termed LP-BM5. Development of splenomegaly and lymphadenopathy, caused primarily by increases in B cell immunoblasts, requires the presence of CD4+ T cells and is assumed to be mediated by lymphokines produced by these cells inasmuch as progression of disease is markedly inhibited by treatment of infected mice with cyclosporin A. Studies of spleen cells from infected mice revealed spontaneous production of cytokines (IFN-gamma, IL-2, IL-4, IL-5, and IL-10) characteristic of Th0 (or a mixture of Th1 and Th2) T helper cells at 1 wk after infection. At later times, IFN-gamma and IL-2, characteristic products of Th1 helper clones, were expressed poorly, either spontaneously or after stimulation of cells with Con A. In contrast, IL-4, IL-5, IL-6, and IL-10, cytokines typically synthesized by Th2 cells, were produced in response to Con A or spontaneously through 18 wk post-infection. Increased serum IgE levels and enhanced IL-10 mRNA expression were consistent with expression of Th2 cytokines at biologically significant levels in vivo. Selective depletion of T cell subsets before stimulation with Con A showed that CD4+ T cells were the primary source of IL-2, IL-4, IL-10, and, to a lesser extent, IFN-gamma in spleens and lymph nodes of normal or infected mice. These results suggest that persistent activation of CD4+ T cells with the lymphokine profile of Th2 helper clones is responsible for chronic B cell stimulation, down-regulation of Th1 cytokines, and impaired CD8+ T cell function in mouse AIDS. This provides the first demonstration that, like many parasitic infections, viruses encoding potent antigenic stimuli can markedly affect the balance of Th subset expression.
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PMID:CD4+ subset regulation in viral infection. Preferential activation of Th2 cells during progression of retrovirus-induced immunodeficiency in mice. 134 85

The IgE synthesis is tightly controlled by a complex network of T and B cells. Because human immunodeficiency virus (HIV) disease associates T cell activation and depletion, polyclonal B cell activation, atopic symptoms, drug hypersensitivity, and autoimmune activity, we have evaluated IgE, as well as IgA, IgG, and IgM, in 315 HIV-seropositive individuals with or without acquired immunodeficiency syndrome (AIDS) and compared the results to those of 100 HIV-seronegative subjects. IgE levels were higher in HIV-infected subjects as a whole, compared to levels in seronegative control subjects (p less than 0.05). This difference was particularly marked between patients with AIDS and control subjects (p less than 0.005). A strong relationship appeared between IgE and the immune status as assessed by CD4 cell counts (p less than 0.001 between IgE values in patients with CD4 less than 300 or greater than 300/microliters). In addition, we assessed the predictive value of IgE elevation over disease progression: in subjects with a CD4 count less than 300/microliters, the survival analysis disclosed a 24-month occurrence rate of AIDS of 83% in individuals with IgE greater than 150 KIU/L versus 44% in individuals with IgE less than 150 (p = 0.016). In subjects with an AIDS-related complex, IgE greater than 150 indicated a 100% rate of AIDS versus 9% in individuals with IgE less than 150 (p = 0.003). Thus, IgE levels appear to be a very discriminative marker between patients in late stages of HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elevation of IgE in HIV-infected subjects: a marker of poor prognosis. 134 48

The majority of patients with common variable immunodeficiency (CVI) have low to normal numbers of membrane Ig-bearing B cells; yet these cells fail to differentiate in vivo resulting in hypogammaglobulinemia. We have suggested that the differentiation failure of CVI B cells is related to a failure to respond appropriately to signals involved in terminal B cell differentiation as most CVI subjects' cells undergo activation and proliferation normally. Whether this failure relates to a direct "intrinsic" defect in the B cells or is secondary to a lack of appropriate T cell or other influences in vivo is uncertain. We have previously reported that the majority of patients with CVI have elevated circulating levels of IL-6. We now show that the IL-6 produced by these patients is functionally normal. Additionally, the display of IL-6 receptors on in vitro stimulated CVI B cells is normal. However, we found that the patients' cells do not make IgE in response to an IL-6/T-cell-dependent differentiation pathway employing exogenous interleukin-4 (IL-4). The failure to respond in the IL-6-dependent system could not be overcome by exogenous IL-6 or varying doses of IL-4. In contrast, when stimulated by CD40 plus IL-4 in a differentiation pathway that does not require IL-6, B cells from CVI patients were stimulated to produce IgE. These findings, along with our earlier data showing that 13-cis-retinoic acid can drive maturation in CVI patients, strengthen the concept that B cells in patients with CVI have the potential for terminal differentiation but do not appear to achieve this in vitro or in vivo through a polyclonal Ig differentiation pathway that employs IL-6 as one of its maturation signals.
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PMID:B cells from subjects with CVI can be driven to Ig production in response to CD40 stimulation. 138 64

Immunotherapy is defined as the controlled exposure to known allergens to reduce the severity of the allergic response. Although available since 1910, its exact mechanisms of action is not known but may involve an increase in allergen-specific IgG antibodies, a decrease in IgE synthesis, and alteration in T-lymphocyte activity. Immunotherapy is indicated in patients with proven allergy who have significant symptoms. It may be used together with pharmacologic measures but is relatively contraindicated in patients receiving beta-blocker therapy. Immunotherapy may be continued during pregnancy and should not be initiated in patients with autoimmune diseases or in human immunodeficiency virus-positive patients. Selection of appropriate diagnostic tests is important. Before immunotherapy is considered, there are two recommended in vivo tests (combined prick and intradermal skin test, and skin end point titration) and two recommended in vitro tests (radioallergosorbent test [RAST] and enzyme-linked immunosorbent assays [ELISA]), all equally safe and sensitive. After appropriate test interpretation, treatment is initiated with slowly escalating doses of allergen. Effects are often apparent in 3 to 6 months and, after continuation for 3 to 5 years, patients usually achieve lasting benefit.
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PMID:Immunotherapy: rationale and mechanisms. 147 Apr 67

Asthma is a multifactorial, reversible, obstructive lung disease that manifests airway inflammation as well as airway hyperreactivity. In addition to IgE-mediated respiratory reactions, the pathophysiology of asthma can be triggered by both viral respiratory and bacterial sinopulmonary infections. Even though most asthma patients do not manifest undue susceptibility to infection, a subset of asthma patients with recurrent sinopulmonary as well as upper-respiratory infections may have an associated immune deficiency syndrome. In a subset of these patients, deficiencies of serum IgG subclasses have also been described in the presence of low-normal or normal serum IgG and also deficient serum IgA. In addition to the usual asthma therapy with beta 2 agonist and theophylline bronchodilators as well as cromolyn and steroids, many of these immunodeficiency patients will benefit from iv gamma-globulin therapy. However, we suggest that an inability to synthesize specific serum antibody to injected vaccines or immunogens be a prerequisite before initiating iv gamma-globulin therapy. The clinician should not rely on serum IgG subclass levels alone as a criterion for initiation of passive immune globulin therapy. There may be another cohort of asthma patients who could benefit from iv gamma-globulin therapy. In a small open-label pilot study severe steroid-dependent asthma patients who were not immunodeficient and did not have undue susceptibility to infection were treated with iv gamma-globulin with a very large dosage protocol of 2000 mg/kg monthly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Asthma. A role for IVIG therapy? 160 21

Two therapeutic modalities, zidovudine (targeting retroviral replication) and cyclosporin A (targeting immunopathologic consequences of retroviral expression) were evaluated in a murine model of AIDS. In previous studies, cyclosporin A treatment (40 or 60 mg/kg/day) before and after infection with LP-BM5 murine leukemia viruses protected against the development of immunodeficiency disease. The present study extends these findings. First, a low dose of cyclosporin A (20 mg/kg/day) was ineffective, and treatment initiated 5 days after infection did not protect against virus-induced lymphoproliferation and hypergammaglobulinemia. Second, zidovudine added to drinking water (0.1 mg initiated 5 days after infection and continued for 8 weeks) was more effective than 0.2 mg/mL given day 5-12 after infection. This treatment reduced lymph node size, disease severity as determined histologically, retrovirus-induced gp70 expression, and IgE (but not IgM and IgG) levels. Third, combined treatment had an additive, protective effect on lymphocyte proliferative capacity. This successful dual therapeutic strategy in a mouse model has potential applicability for similar approaches in treating human immunodeficiency virus infection.
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PMID:Effect of cyclosporin A and zidovudine on immune abnormalities observed in the murine acquired immunodeficiency syndrome. 163

We studied 13 patients with human immunodeficiency virus (HIV) infection and a chronic pruritic folliculitis that was unresponsive to systemic treatment with bactericidal anti-staphylococcal antibiotics. The skin eruption was characterized by multiple urticarial follicular papules scattered on the trunk (100%), the head and neck (85%), and the proximal aspect of the extremities (62%). Absolute peripheral eosinophil counts were increased in six of 13 patients; a relative peripheral eosinophilia was present in 10 of 13 patients. Serum IgE levels were elevated in all seven patients tested (range, 88 to 9050 IU). Histopathologic features included a folliculitis with eosinophils. Pathogenic bacteria were not consistently found by routine bacterial skin cultures, cultures of skin biopsy specimens, or histopathologic evaluation. CD4 counts were decreased in all of the 12 patients tested (less than 300 cells per cubic millimeter) and were below 250 cells per cubic millimeter in 10 patients. A clinical response was noted to astemizole, to ultraviolet light in the B range, and to topical clobetasol propionate. These observations demonstrate that HIV-associated eosinophilic folliculitis is a unique HIV-related cutaneous disorder that is characterized by a culture-negative, chronic, pruritic folliculitis and a characteristic histopathologic picture. Of special importance, because it is associated with CD4 counts of less than 250 to 300 cells per cubic millimeter, eosinophilic folliculitis appears to be an important clinical marker of HIV infection and, particularly, of patients at increased risk of developing opportunistic infections. We suggest that the term eosinophilic pustular folliculitis (Ofuji's disease), previously used to describe this dermatosis in HIV-infected patients, should be discarded.
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PMID:Human immunodeficiency virus-associated eosinophilic folliculitis. A unique dermatosis associated with advanced human immunodeficiency virus infection. 167 28

Drug allergy is the most common and significant allergic manifestation of HIV3 infection. Initially described in patients treated with SMX-TMP for PCP, allergy is now known to involve a multitude of drugs. The pathogenesis of, and risk factors for, allergy in HIV infection are poorly understood, although there is evidence suggesting that allergy is more common with advancing immunodeficiency. HIV-negative subjects with sulfonamide allergy may have drug-specific antibodies and drug metabolite-induced lymphocyte cytotoxicity, abnormalities that could partly explain the allergic mechanisms and which may have future diagnostic potential; these abnormalities have not been described in HIV-infected subjects. Therapy includes avoidance, suppressive agents such as corticosteroids, and desensitization, although the appropriate role for each is not entirely clear. Serum IgE levels have been shown to rise with progressive disease; those patients with higher levels may have a worse prognosis. The mechanisms of this rise are multifactorial, probably a combination of altered T-lymphocyte regulation of IgE synthesis and of production of specific IgE directed against microbial antigens.
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PMID:Allergic manifestations of human immunodeficiency virus (HIV) infection. 167 34

The mechanisms of genetic control of IgE responses are exercised at different immuno-physiological levels. This study centered upon the development of IgE lineage-specific regulatory T cells. Herein, we demonstrate the following points: (a) perinatal administration of soluble self IgE molecule or self IgE complexed with foreign antigen induces IgE tolerance as manifested by antigen-specific IgE unresponsiveness and a generalized IgE immunodeficiency, and the induction of IgE tolerance does not affect antigen-specific IgG1, IgG, and IgA responses; (b) inducibility of perinatal IgE tolerance is correlated with complete absence of endogenously secreted IgE in the neonates; and the state of persistent IgE tolerance also does not correlate with the presence of high levels of circulating anti-IgE autoantibodies; (c) The lesions induced during the ontogeny of IgE antibody system do not appear to result from an imbalance of production of interleukin 4 and interferon-gamma by T helper Th2 and Th1 cells in antigen-stimulated cultures; the dual immunoregulatory lesions in T cell subsets are demonstrated: clonal anergy/deletion of CD4+ IgE Th cells and the presence of CD8+ IgE suppressor cells induced by perinatal IgE treatment. We propose that antigen/interleukin 4 activated B cells are controlled by IgE lineage-specific regulatory T cells which recognize self IgE determinant(s) on IgE committed B cells. Life-long IgE tolerance ensues as a result of a new steady state of IgE lineage-specific CD4+ and CD8+ T cell subsets.
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PMID:Mechanisms of IgE tolerance: dual regulatory T cell lesions in perinatal IgE tolerance. 168 Jun 99


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