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)

21 seroconversion HIV-infected subjects have been examined. 16 of them presented with acute symptoms. The disease in the period of seroconversion manifested with fever, weakness, headache, pain in the throat, enlargement of peripheral lymph nodes, polymorphous eruption. Typical mononucleosis-like syndrome occurred in 3 patients only. Half of the patients had subclinical disease, no eruption was seen. Because of clinical indications only 8 of 21 patients were examined for HIV infection. One-third of the patients in seroconversion had moderate thrombocytopenia, probably of autoimmune nature. Autoimmune disorder of the thyroid was registered in 1 patient. The diagnosis of acute HIV infection is not easy in view of rare occurrence of immunodeficiency typical for this infection. Candidiasis of the mucosa was seen in 37.5%, low levels of CD4-lymphocytes in 66.7% of the cases.
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PMID:[The clinical manifestations of HIV infection during seroconversion]. 857 Dec 43

Studies of the biological effects of Fas signaling, using transformed cell lines as targets, indicate that ligation of the Fas receptor induces an apoptotic death signal. Chronically activated normal human T cells are also susceptible to Fas-mediated apoptosis. However, interactions between Fas and Fas ligand can also yield a costimulatory signal. Here, David Lynch, Fred Ramsdell and Mark Alderson present a model for the role of As and FasL in the homeostatic regulation of normal immune responses. They discuss how dysregulation of the Fas apoptotic pathway may contribute to certain disease states, including autoimmune disease and human immunodeficiency virus (HIV)-induced depletion of CD4+ T cells.
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PMID:Fas and FasL in the homeostatic regulation of immune responses. 876 24

Autoantibodies directed against peptide-defined epitopes of T-cell receptors occur in the serum of healthy humans with the levels and isotypic expression dependent upon physiological changes (aging, pregnancy) or upon the development of autoimmune disease. We carried out investigations of autoantibodies against Tcr peptide-defined epitopes in retroviral infections of humans (HIV-1) and mice (LP-BM5 strain of murine leukemia virus) to determine whether infection with these agents disrupted the regulation of the production of these antibodies. Retroviral infection in humans resulted in increased levels of autoantibody production against putative immunoregulatory regions of the Tcr beta chain (V beta CDR1 and Fr3), a result reflecting a disruption of regulation. In addition, antigenic mimicry was observed with a cross-reaction shared between the common portion of the V3 neutralizing loop of the HIV-1 gp120 molecule and the joining segment of T-cell receptors (J beta). Infection of mice with the defective retrovirus resulted in the induction of antibodies directed particularly against V beta CDR1 peptide-defined determinants. Analysis of the virally induced response to a set of 8 CDR1 peptide epitopes indicated a selectivity to the process. It was possible to partially reverse aberrant cytokine changes correlated with the onset of murine MAIDS by administration of T-cell receptor peptides in saline. These results show that retroviral infection in humans and mice has a profound dysfunctional effect on the regulation of autoantibodies to T-cell receptors. The function of these autoantibodies in the immunopathogenesis of acquired immunodeficiency remains to be determined.
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PMID:Autoantibodies against peptide-defined epitopes of T-cell receptors in retrovirally infected humans and mice. 864 4

Motheaten mice homozygous for the recessive mev mutation develop a fatal immunodeficiency syndrome associated with hypergammaglobulinemia, thymic aplasia, production of autoantibodies and development of a severe lupus like systemic autoimmune disease. Most B lymphocytes in this mutant strain belong to B-1 subset. We have addressed the question if differences existed in the V-gene repertoire of autoimmune mev/mev mice as compared to phenotypically normal mev/+ and C57BL/6 background strain by examining the VH and V kappa gene family expression as well as the association of VH and V kappa gene families among B lymphocyte clones. The data outlined here demonstrate that both the expression of VH and V kappa gene families and their association is skewed in mev/mev mice, suffering from systemic autoimmune disease, and differs significantly from phenotypically normal mev/+ litter mates as well as the C57BL/6 background strain. In addition, VH+V kappa gene family pairs in phenotypically normal mev/+ differed from normal C57BL/6 mice suggesting that motheaten mutation, whether homozygous or heterozygous, alters the development of the B lymphocyte repertoire. These observations suggest positive selection of B-1 lymphocytes in autoimmune motheaten mice either as a result of selective processes, via receptor-ligand interactions, operating on the development of the primary antibody repertoire or defective B lymphocyte haematopoiesis due to the deficiency of haematopoietic cell phosphatase involved in determining the threshold by which B cells respond to self antigen(s).
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PMID:Skewed VH and V kappa gene family expression and pairing occurs among B lymphocytes in autoimmune motheaten mice. 882 76

An increased incidence of non-Hodgkin's lymphoma is seen in patients with immunodeficiency from any cause. The majority of these are high grade B-cell lymphoma and most are associated with the Epstein-Barr virus (EBV). In post-transplant lymphoma/lymphoproliferative disorders the tumour may regress following reduction of immuno-suppression but in AIDS the lymphomas show a characteristic aggressive course and poor prognosis. We describe low grade B-cell gastric lymphoma of mucosa associated lymphoid tissue (MALT) in three immunocompromised patients (two post-transplant, one HIV positive). In each case, the tumour showed classical morphological features of gastric MALT lymphoma and was not associated with EBV. Helicobacter pylori was identified in each case. Clinical follow-up suggests that the behaviour in these tumours is similar to that seen in MALT lymphomas in immunocompetent patients and not typical of the lymphomas usually associated with immunosuppression. Although the finding of MALT lymphoma in immunosuppressed patients might be coincidental, the association of some MALT lymphomas with autoimmune disease suggests that dysregulation of the immune system might play a role in the pathogenesis of these tumours.
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PMID:Low grade gastric B-cell lymphoma of mucosa associated lymphoid tissue in immunocompromised patients. 887 60

We report the case of a 26-year-old man with haemophilia B and human immunodeficiency virus infection (HIV) who presented with a short history of multiple dermatofibromas. He also had troublesome psoriasis for which he was receiving acitretin with UVB therapy and had recently discontinued low-dose daily prednisolone for associated arthropathy. Multiple dermatofibromas are rare and have been reported previously in association with autoimmune disease, especially in individuals receiving immunosuppressive therapy. We believe this to be the first report of multiple dermatofibromas in an individual with advanced HIV infection and propose that it may be related to his viral-mediated immunodeficiency, possibly augmented by UVB and systemic corticosteroid therapy.
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PMID:Multiple dermatofibromas in a patient with HIV infection. 885 40

The molecular mechanisms of the primary immunodeficiencies have been further explored and provide insights into the regulation of the immune response and its role in autoimmune disease, infection, and malignancy. The critical role of CD40-CD40 ligand-mediated effects in T cell-dependent B cell activation, shown through the study of patients with common variable immunodeficiency and hyper IgM syndrome, suggests a potential narrow target for immunomodulatory therapy. A mouse model for chronic granulomatous disease has been developed and promises to be a source of future information. Optimal cost-effective therapy for primary immunodeficiencies continues to be defined, with the results of a large series of patients treated with subcutaneous immunoglobulin infusions reported. Further experience with polyethylene glycol adenosine deaminase and interleukin-2 conjugates is discussed.
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PMID:Immunodeficient states and associated rheumatic manifestations. 886 40

Current evidence indicates that the neuroendocrine system is the highest regulator of immune/inflammatory reactions. Prolactin and growth hormone stimulate the production of leukocytes, including lymphocytes, and maintain immunocompetence. The hypothalamus-pituitary-adrenal axis constitutes the most powerful circuit regulating the immune system. The neuropeptides constituting this axis, namely corticotrophin releasing factor, adrenocorticotrophic hormone, alpha-melanocyte stimulating hormone, and beta-endorphin are powerful immunoregulators, which have a direct regulatory effect on lymphoid cells, regulating immune reactions by the stimulation of immunoregulatory hormones (glucocorticoids) and also by acting on the central nervous system which in turn generates immunoregulatory nerve impulses. Peptidergic nerves are major regulators of the inflammatory response. Substance P and calcitonin gene-related peptide are pro-inflammatory mediators and somatostatin is anti-inflammatory. The neuroendocrine regulation of the inflammatory response is of major significance from the point of view of immune homeostasis. Malfunction of this circuit leads to disease and often is life-threatening. The immune system emits signals towards the neuroendocrine system by cytokine mediators which reach significant blood levels (cytokine-hormones) during systemic immune/inflammatory reactions. Interleukin-1, -6, and TNF-alpha are the major cytokine hormones mediating the acute phase response. These cytokines induce profound neuroendocrine and metabolic changes by interacting with the central nervous system and with many other organs and tissues in the body. Corticotrophin releasing factor functions under these conditions as a major co-ordinator of the response and is responsible for activating the ACTH-adrenal axis for regulating fever and for other CNS effects leading to a sympathetic outflow. Increased ACTH secretion leads to glucocorticoid production. alpha-melanocyte stimulating hormone functions under these conditions as a cytokine antagonist and an anti-pyretic hormone. The sympathetic outflow, in conjunction with increased adrenal activity. leads to the elevation of catecholamines in the bloodstream and in tissues. Current evidence suggests that neuroimmune mechanisms are essential in normal physiology, such as tissue turnover, involution, atrophy, intestinal function, and reproduction. Host defence against infection, trauma and shock relies heavily on the neuroimmunoregulatory network. Moreover, abnormalities of neuroimmunoregulation contribute to the aetiology of autoimmune disease, chronic inflammatory disease, immunodeficiency, allergy, and asthma. Finally, neuroimmune mechanisms play an important role in regeneration and healing.
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PMID:The immune effects of neuropeptides. 891 48

Endogenous retroviruses (ERVs) are estimated to comprise up to 1% of human DNA. While the genome of many ERVs is interrupted by termination codons, deletions or frame shift mutations, some ERVs are transcriptionally active and recent studies reveal protein expression or particle formation by human ERVs. ERVs have been implicated as aetiological agents of autoimmune disease, because of their structural and sequence similarities to exogenous retroviruses associated with immune dysregulation and their tissue-specific or differentiation-dependent expression. In fact, retrovirus-like particles distinct from those of known exogenous retroviruses and immune responses to ERV proteins have been observed in autoimmune disease. Quantitatively or structurally aberrant expression of normally cryptic ERVs, induced by environmental or endogenous factors, could initiate autoimmunity through direct or indirect mechanisms. ERVs may lead to immune dysregulation as insertional mutagens or cis-regulatory elements of cellular genes involved in immune function. ERVs may also encode elements like tax in human T-lymphotrophic virus type I (HTLV-I) or tat in human immunodeficiency virus-I (HIV-I) that are capable of transactivating cellular genes. More directly, human ERV gene products themselves may be immunologically active, by analogy with the superantigen activity in the long terminal repeat (LTR) of mouse mammary tumour viruses (MMTV) and the non-specific immunosuppressive activity in mammalian type C retrovirus env protein. Alternatively, increased expression of an ERV protein, or expression of a novel ERV protein not expressed in the thymus during acquisition of immune tolerance, may lead to its perception as a neoantigen. Paraneoplastic syndromes raise the possibility that novel ERV-encoded epitopes expressed by a tumour elicit immunity to cross-reactive epitopes in normal tissues. Recombination events between different but related ERVs, to whose products the host is immunologically tolerant, may also generate new antigenic determinants. Frequently reported humoral immunity to exogenous retrovirus proteins in autoimmune disease could be elicited by cross-reactive ERV proteins. A review of the evidence implicating ERVs in immune dysfunction leads to the conclusion that direct molecular studies are likely to establish a pathogenic role for ERVs in autoimmune disease.
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PMID:The potential roles of endogenous retroviruses in autoimmunity. 893 Jun 74

There is a paradoxical relationship between immunodeficiency diseases and autoimmunity. While not all individuals with immunodeficiency develop autoimmunity, nor are all individuals with autoimmunity immunodeficient, defects within certain components of the immune system carry a high risk for the development of autoimmune disease. Inherited deficiencies of the complement system have a high incidence of systemic lupus erythematosus (SLE), glomerulonephritis, and vasculitis. Carrier mothers of children with chronic granulomatous disease, an X-linked defect of phagocytosis, often develop discoid lupus. Several antibody deficiencies are associated with autoimmune disease. Autoimmune cytopenias are commonly observed in individuals with selective IgA deficiency and common variable immune deficiency. Polyarticular arthritis can be seen in children with X-linked agammaglobulinemia. Combined cellular and antibody deficiencies, such as Wiskott-Aldrich syndrome, carry an increased risk for juvenile rheumatoid arthritis and autoimmune hemolytic anemia. Several hypothetical mechanisms have been proposed to explain the associations between autoimmunity and immunodeficiency. Immunologic defects may result in a failure to exclude microbial antigens, resulting in chronic immunologic activation and autoimmune symptoms. There may be shared genetic factors, such as common HLA alleles, which predispose an individual to both autoimmunity and immunodeficiency. Defects within one component of the immune system may alter the way a pathogen induces an immune response and lead to an inflammatory response directed at self-antigens. An understanding of the immunologic defects that contribute to the development of autoimmunity will provide an insight into the pathogenesis of the autoimmune process.
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PMID:The association between immunodeficiency and the development of autoimmune disease. 893 26


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