Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004364 (autoimmune disease)
 24,845 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the last few years, molecular genetics analyses have permitted novel insights into psoriasis, a disease characterized by uncontrolled proliferation of keratinocytes and recruitment of T cells into the skin. The disease affects approximately 1-2% of the Caucasian population and can occur in association with other inflammatory diseases such as Crohn's disease and in association with human immunodeficiency virus (HIV) infection. Given that psoriasis has characteristics of an autoimmune disease, it is not surprising that HLA studies revealed an association with certain alleles, notably HLA-Cw6. Despite this HLA component, psoriasis in some families is inherited as an autosomal dominant trait with high penetrance. Loci at chromosome 17q25 and 4q have been identified following genome-wide linkage scans of large, multiply affected families. In the case of at least the susceptibility locus at 17q25, the development of psoriasis does not require the presence of HLA-Cw6. Sib-pair analyses have confirmed the association with HLA-Cw6, confirmed the existence of a locus at 17q25 and identified other possible susceptibility loci. Two independent groups have reported a third region on chromosome 20p. Despite these findings, the extent of genetic heterogeneity and the role of environmental triggers and modifier genes is still not clear. The precise role of HLA also still needs to be defined. The isolation of novel susceptibility genes will provide insights into the precise biochemical pathways that control this disease. Such pathways will also reveal additional candidate genes that can be tested for molecular alterations resulting in disease susceptibility.
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PMID:The genetics of psoriasis: a complex disorder of the skin and immune system. 973 74

Assessing the functionality of T lymphocytes is important in determining progression rate in human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), transplant rejection, and autoimmune disease. Activation of T-cells in response to antigen results in expression of cytokines and cytokine receptors, proliferation, and development of effector function. Multiplexed flow cytometric analyses were developed to measure cytokine receptor expression, internal cytokine expression, and cytokine secretion by activated T-cells in vitro. Receptor expression was determined by the binding of phycoerythrin-labeled cytokines. Internal cytokine was determined by intracellular labeling with anti-cytokine antibodies. Cytokine secretion was determined by a flow cytometry-based immunofluorescence assay. The assays could be multiplexed, measuring up to six cytokines simultaneously and measuring cellular receptor expression simultaneously with cytokine secretion. The immunoassays were sensitive in the femtomolar range, allowing determination of normal serum levels of cytokines (<100 fg/ml). Using granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion as a marker for activation, it was determined that at peak secretion (68 h post activation) an average of 1,150 molecules of GM-CSF were produced per cell per hour. Active infection with several viruses reduced the ability of T-cells to be activated. Activated T-cells (1 x 10(6)) normally produced 4-8 pg/ml/h GM-CSF after 20 h of activation, impaired T-function resulted in a decrease to the 0.2-2.0 pg/ml/h range.
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PMID:T-lymphocyte functionality assessed by analysis of cytokine receptor expression, intracellular cytokine expression, and femtomolar detection of cytokine secretion by quantitative flow cytometry. 977 87

BMT can both transmit and eliminate autoimmune diseases, and hence it has been suggested as an optional treatment for severe autoimmune conditions. In this communication we deal with the question of whether chronic GVHD is an autoimmune disease in itself, review the literature reports of autoimmune diseases following BMT in humans, and describe the autoimmune nature of the post-BMT state. Chronic GVHD, which is a frequent complication post-BMT, has clinical and pathogenic characteristics similar to autoimmune diseases, such as scleroderma and Sjogren's syndrome. Although the pathogenesis of chronic GVHD is not yet clear, thymic damage induced by acute GVHD may contribute to both the immunodeficiency and autoimmunity characterising chronic GVHD. A similar phenomenon is syngeneic GVHD, which results from an imbalance between autoreactive and autoregulatory lymphocytes. Additionally, other autoimmune diseases have been reported in post-BMT patients, and among these the most common are hypothyroidism, hyperthyroidism, myasthenia gravis and immune cytopenias. Although these diseases also occur also outside the post-BMT setting, they are unique with respect to pathogenesis (no association between myasthenia gravis and thymic pathology), diagnosis (symptoms of hyperthyroidism may be inadvertently related to other conditions), and prognosis (post-BMT autoimmune cytopenias may be fatal and treatment non-responsive). Nevertheless, many other autoimmune diseases have been reported after BMT, and these are mainly presented as case reports. Regarding the mechanism of post-BMT autoimmunity, the minority of cases stem from donor-related transfer of pathogenic lymphocytes or their progenitors, while most of the cases (either chronic GVHD or specific diseases) can be attributed to the immunologic imbalances characterising the post-BMT setting. The factors that may expose an individual to autoimmunity development post-BMT include genetic predisposition, an environmental factor such as CMV, and the nature of the donor who may aid in creating microchimerism and subsequently chronic GVHD and its related autoimmune manifestations.
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PMID:Autoimmune diseases and autoimmunity post-bone marrow transplantation. 982 15

A 56-year-old man was admitted to our hospital in December 1996 due to empyema thoracis. A laboratory examination revealed lymphocytopenia and CD4+ T lymphocytopenia (<300 cells/ microl). No evidence for a human immunodeficiency virus (HIV) infection was found. No malignant, hematological or autoimmune disease was detected. We thus diagnosed this case as being idiopathic CD4+ T lymphocytopenia (ICL). During his hospital treatment, he was affected with cytomegaloviral retinitis and cured by therapy. His subsequent treatment went well without a recurrence of severe infection although a low CD4+ T lymphocyte count continued after the recovery from empyema thoracis.
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PMID:Idiopathic CD4+ T lymphocytopenia disclosed by the onset of empyema thoracis. 1005 41

Cell-to-cell signals between T lymphocytes and antigen-presenting cells strictly regulate the development of the immune response. It has clearly emerged that among these signals few cell surface receptor-ligand pairs, such as CD40 and its ligand, CD154, are mandatory for the induction of lymphocyte activation. The early observation that mutations of CD154 gene are responsible for a human severe immunodeficiency primed an impressive number of studies aimed to functionally characterize this receptorial system in view of therapeutically exploiting its properties. Indeed, various approaches aimed to disrupt natural CD40-CD154 interaction were highly effective in the prevention and treatment of several experimental models of autoimmune disease and transplant rejection. In parallel, abnormalities of this pathway were constantly found in several immunologically-mediated human diseases. Furthermore, a number of studies have dissected the role of CD40 and its ligand in the immune response against various microbial and viral pathogens. Since these molecules are often expressed by tumor cells, it is not surprising that great efforts have been made to address their function also in the development of cancer. Most recent data strongly suggest an involvement of endothelial CD40 in the vascular processes that lead to atherogenesis. This review focuses on the most significant advances in the understanding of the molecular regulatory events involving CD40 and its ligand in experimental and human disease.
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PMID:CD40-CD154 interaction in experimental and human disease (review). 1008 5

Recent studies indicate that fetal cells persist in maternal blood for decades after pregnancy. Maternal cells are known to engraft and persist in infants with immunodeficiency, but whether maternal cells persist long-term in immunocompetent offspring has not specifically been investigated. We developed sensitive human leukocyte antigen-specific (HLA-specific) PCR assays and targeted nonshared maternal HLA genes to test for persistent maternal microchimerism in subjects with scleroderma and in healthy normal subjects. Nonshared maternal-specific DNA was found in 6 of 9 scleroderma patients. In situ hybridization with double labeling for X and Y chromosome-specific sequences revealed female cells in peripheral blood samples from 2 male scleroderma patients. HLA-specific PCR also frequently revealed persistent maternal microchimerism in healthy control subjects. The mean age of all subjects with maternal microchimerism was 28 years (range: 9-49 years). With few exceptions, mothers of subjects with persistent maternal microchimerism were HLA incompatible with subjects for class I and class II alleles. These results clearly indicate that HLA-disparate maternal cells can persist in immunocompetent offspring well into adult life. The biological significance of maternal microchimerism and whether it might contribute to autoimmune disease requires further investigation.
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PMID:Microchimerism of maternal origin persists into adult life. 1039 97

The predominant itchy folliculitis associated with human immunodeficiency virus (HIV) infection appears to be an eosinophilic folliculitis (EF). This is characterized by lytic degeneration of sebaceous glands and an inflammatory infiltrate in which eosinophils and CD8+ T lymphocytes predominate. All patients have low CD4 counts and present late on in their HIV disease. Lesional distribution is mainly truncal, with a significant proportion also having facial involvement. Our prospective survey has shown that it is impossible to differentiate clinically between infective folliculitis and EF, and we recommend therefore that all cases are biopsied. We review the clinicopathological and immunological aspects of HIV-associated itchy folliculitis, in particular HIV-associated EF as well as current theories on pathogenesis and treatment. We suggest that HIV-associated EF is an autoimmune disease with the sebocyte or some constituent of sebum acting as the autoantigen.
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PMID:Itchy folliculitis and human immunodeficiency virus infection: clinicopathological and immunological features, pathogenesis and treatment. 1041 9

Human thymoma is a neoplasm of thymic epithelial cells associated with several clinical syndromes ranging from autoimmune disease to immunodeficiency. The aim of our research was to investigate T cell-mediated immune response in patients with thymoma. Initially eight patients were enrolled in this study. Four patients underwent surgical removal of the thymus, while four were submitted to diagnostic procedures only. Inversion of the CD4:CD8 ratio was found in three patients. Only one subject displayed a normal CD19 count in peripheral blood. The mean value (+/-SD) of the CD19 percentage in the patient group was 2 +/- 2.2. Notably, the patients with thymoma had fewer mature B lymphocytes than the thymectomized patients. The T-cell receptor (TCR) repertoire was investigated in three individuals affected by thymoma: one underwent thymectomy, while the two others, one of which presented with lymphocytosis, were submitted to diagnostic biopsies only. The preliminary results showed a marked alteration in the CD8 repertoire of the thymectomized patient but not in that of the lymphocytotic patient. However, alterations in the TCR repertoire were also found in one patient with thymoma. Altogether, these preliminary findings reveal that loss of CD19+ lymphocytes in peripheral blood is a frequent phenomena in thymoma patients. In this article we discuss this aspect in the context of alterations of the TCR repertoire.
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PMID:Immunological findings in thymoma and thymoma-related syndromes. 1057 62

Profound and complex changes in the immune response occur during the aging process. Immunosenescence is reflected by a sum of disregulations of the immune system and its interaction with other systems. Many of the changes would appear to implicate age-related deficiencies of the immune responses. The term immunosenescence designates therefore a sort of deterioration of the immune function which is believed to manifest itself in the increased susceptibility to cancer, autoimmune disease, and infectious disease. Evidence has been accumulating from several studies which suggest an association between immune function and individual longevity. However, there are observations, especially in very old healthy people, that several immune functions are unexpectedly well preserved and substantially comparable to those observed in young subjects. These findings raise the question of whether the alterations that can be observed in the immune parameters of the elderly are a cause or a result of underlying disease processes. Moreover, studies on centenarians revealed a remodeling of the immune system rather than a deterioration, suggesting that the changes observed during immunosenescence do not correspond to immunodeficiency. The underlying mechanisms of these events are however still unclear. The purpose of the present review is to assess the status of research on the immunobiology of aging. In this first section, we focus attention on the B cell biology of aging. In clinical practice, the changes in humoral immune responsiveness and antibody-mediated defense mechanisms could greatly influence the incidence and outcome of bacterial infections and autoimmune diseases as well as the response to vaccines.
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PMID:The immune system in the elderly: I. Specific humoral immunity. 1058 Jun 35

Granulocyte-macrophage colony stimulating factor (GM-CSF) facilitates the induction of primary immune responses by activating and recruiting antigen-presenting cells (APC), which efficiently present antigen determinants to Th cells. We have derived a functional GM-CSF/gp120 chimeric protein that, following immunization in soluble, adjuvant-independent form in normal mice, triggers highly specific, high affinity anti-gp120 antibodies. In contrast, nude mice respond with mutated, polyreactive, low affinity antibodies that mature further and increase in affinity in T cell-reconstituted nude mice. Anti-gp120 antibody production in nude mice is mediated principally by GM-CSF/gp120-triggered IL-4 production, since neutralizing anti-IL-4 abrogates the in vivo response. The anti-gp120 antibody response in normal, nude and T cell-reconstituted nude mice is encoded at a remarkably high frequency by the VH81X and VH7183 genes, a family used notably during fetal life and, when expressed at the adult stage, associated with autoimmune disease. We conclude that HIV gp120 binds and selects a subpopulation of developing B cells expressing a set of VH genes associated with immunodeficiency and autoimmunity.
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PMID:Antibody repertoire against HIV-1 gp120 triggered in nude and normal mice by GM-CSF/gp120 immunization. 1059 11


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