Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the decade since the early 1980s, the increasing use of immunosuppressive therapy for cancer and autoimmune disease, as well as for organ transplantation, has combined with the acquired immunodeficiency syndrome epidemic to increase greatly the incidence of opportunistic infections and other complications of the gastrointestinal tract. Consequently, barium fluoroscopic and cross-sectional imaging studies tailored to address these problems are no longer uncommon. Although overlap exists, there are radiographic patterns that can direct the diagnosis to an opportunistic infection and sometimes to a specific pathogen. This article describes and illustrates the radiographic findings of gastrointestinal superinfection with Candida albicans, cytomegalovirus, Cryptosporidium spp, herpes simplex virus, Mycobacterium tuberculosis, M avium-intracellulare, and human immunodeficiency virus. Other gastrointestinal tract complications of immunosuppression are discussed, including graft-versus-host disease following bone marrow transplantation, typhlitis, and pseudomembranous colitis.
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PMID:Gastrointestinal tract in the immunocompromised host: opportunistic infections and other complications. 141 Mar 32

Acute inflammatory demyelinating polyneuropathy (AIDP) appeared in two patients following allogeneic bone marrow transplantation (BMT). In one transplanted patient (but not in the donor) T cells were sensitized against peripheral nervous system myelin. This could reflect a change in the T cell repertoire in a different milieu. In this context, AIDP might be part of graft-versus-host disease or another associated autoimmune disorder following BMT.
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PMID:Acute inflammatory demyelinating polyneuropathy following bone marrow transplantation. 175 30

Lethally irradiated rats, reconstituted with syngeneic bone marrow and given Cyclosporin A (CyA) for 6 weeks, developed disease resembling allogeneic graft-versus-host disease 2 weeks after withdrawal of CyA. Other studies have demonstrated the pivotal role of the thymus in the etiology of this CyA-induced autoimmune disease (CyA-AI). In this study the question was addressed whether inducer/effector cells of CyA-AI are generated in the thymus during or after CyA administration; whether these cells stay in the thymus, or, if they don't, whether they home to the secondary lymphoid organs. Adoptive transfer of thymocytes from donors treated for induction of CyA-AI obtained one and 14 days after cessation of CyA administration did not elicit CyA-AI in irradiated secondary recipients. Furthermore, adult thymectomy of rats immediately after the course of CyA did not influence the kinetics of development of skin pathology, although weight loss commenced later in thymectomized than in sham-thymectomized rats. Lymph node and spleen cells obtained from donors treated for induction of CyA-AI one and 14 days after withdrawal of CyA-AI caused CyA-AI upon adoptive transfer to secondary recipients, but the symptoms of acute disease (dermatitis, alopecia and weight loss) were strikingly less severe upon transfer of lymphoid cells obtained one day after stopping CyA than 14 days thereafter. Therefore, this study demonstrates that CyA-AI inducer/effector cells are generated in the thymus during the administration of CyA. These cells exit from the thymus during CyA administration; either they home predominantly peripherally (i.e. in the skin) rather than in the secondary lymphoid organs, or they leave the thymus as inducer cells which home in the lymphoid organs where they subsequently may trigger potentially autoreactive lymphocytes as probably also present in normal individuals, or both pathways may be operative.
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PMID:On the localization of effector cells in cyclosporin-induced autoimmunity. 177 63

Microbial superantigens (SA), bound to human B cell surface MHC class II molecules, have been shown to promote direct, "cognate" interaction with SA-reactive autologous Th cells, resulting in polyclonal Ig production. To investigate the potential for microbial SA to support Th cell-dependent, Ag-specific antibody responses, we have extended our studies to the murine system. BALB/c Th cell lines (TCL), specific for either the Mycoplasma arthritis-derived SA or the Staphylococcus aureus-derived toxic shock syndrome toxin-1) were generated. These TCL cells are SA-specific, functionally noncross-reactive, and utilize distinct TCR V beta gene families. Coculture of SA-reactive TCL cells and syngeneic B cells bearing the relevant SA results in B cell proliferation and polyclonal IgM and IgG production. In contrast, Ag-specific (SRBC-specific) antibody-forming cells are only generated in cultures that also contain SRBC. Thus, microbial SA-mediated Th-B cell interactions induce both polyclonal B cell activation and provide selective help for the proliferation and/or differentiation of B cells that have encountered specific Ag. In additional studies, we determined that the in vivo administration of toxic shock syndrome toxin-1 to young, athymic (nude) BALB/c mice results in SA binding to splenic B cells, rendering these B cells effective stimulators of and targets for SA-reactive helper TCL cells. Taken together, these results demonstrate that microbial SA mediate productive Th-B cell interactions analogous to those that occur during allospecific Th-B cell interactions in vitro and GVHD in vivo. These findings are consistent with the hypothesis that microbial SA represent environmental factors that may trigger autoimmune disease in the genetically susceptible host.
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PMID:T helper cell-dependent, microbial superantigen-induced murine B cell activation: polyclonal and antigen-specific antibody responses. 183 62

This report investigates the effects of cyclosporine on the reconstitution of T lymphocytes after syngeneic bone marrow transplantation and its role in the development of a novel T cell-mediated autoimmune disease, syngeneic graft versus host disease. We analyzed the effect of CsA treatment on T lymphocyte differentiation during reconstitution after bone marrow transplantation and correlated the maturation of CD4+ and CD8+ T cell subsets with the onset of syngeneic GVHD. Administration of CsA following syngeneic bone marrow transplantation leads to a developmental arrest of mature CD4+ and CD8+ T lymphocytes in the thymus and a marked reduction in cells expressing the alpha beta T cell receptor. The reduction of CD4+ and CD8+ T cell subsets is also reflected in the peripheral lymphoid compartment with an altered CD4/CD8 ratio. Functional assessment of the cells revealed that CD8+ cells respond normally to mitogenic signalling whereas CD4+ cells exhibit marginal proliferative responses. Both subsets of T lymphocytes respond to syngeneic B lymphoblasts, comparable to the response of T lymphocytes from non-CsA-treated syngeneic BMT recipients, suggesting that autoreactive cells are produced despite CsA treatment. Following discontinuation of CsA, T cell differentiation in the thymus is rapidly restored to normal. However, concurrent with the onset of syngeneic GVHD, a compensatory insurgence of CD4+ T helper cells is observed.
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PMID:Effect of cyclosporine on T lymphocyte development. Relationship to syngeneic graft-versus-host disease. 189 96

Cyclosporine (CS) is a potent immunosuppressive agent which under some circumstances paradoxically augments DTH responses, aggravates some autoimmune diseases, and induces specific forms of autoimmunity. The enhancement of DTH and other immune responses is closely related to the timing of CS administration relative to immunization. CS inhibits IL-2 production (and several other lymphokines) at a pretranscriptional level, but does not usually prevent the antigen-specific priming of T cells, such that T cells may be poised to respond as soon as CS is withdrawn. Thus, accelerated GVHD and allograft rejection may occur after withdrawal of CS. CS has been shown to aggravate and/or induce relapse in several autoimmune diseases including collagen-induced arthritis, EAE, autoimmune thyroiditis, uveitis in SDA chickens, and an autoimmune form of myocarditis in mice. CS may enhance immune responses by inactivating suppressor cells, by altering Th1/Th2 antagonism (e.g., CS promotes a protective Th1-type response in BALB/c mice infected with Leishmania major), or by promoting T cell activation through a CS-resistant IL-2-independent T cell activation/differentiation pathway. At least three forms of CS-induced autoimmunity have been described: Syngeneic or autologous GVHD which occurs in CS-treated syngeneic or autologous bone marrow transplant recipients after CS is withdrawn in rats, mice, and humans; a systemic autoimmune disease with polyarthritis and glomerulonephritis which occurs in irradiated CBA/N mice treated with CS; and organ-specific autoimmune diseases which occur in mice treated with CS during the neonatal period. The precise mechanisms by which CS induces these autoimmune diseases are not clear, however, CS affects immune tolerance at three levels. CS induces thymic medullary involution with loss of medullary Ia+ cells, and appears to at least partially block the transition from double positive (CD4+CD8+) to single positive (mature type) thymocytes. In syngeneic bone marrow chimeras, CS appears to inhibit the intrathymic deletion of clones with relatively low affinity, but not those with high affinity, to self antigens. CS appears to inhibit the action of suppressor T cells which normally maintain an innate form of resistance to autoimmunity. Finally, CS has been shown to prevent the development of T cell clonal anergy. There is redundancy in immune tolerance mechanisms, i.e., clonal deletion, clonal anergy, and suppressor cells can each maintain tolerance to similar antigens, such that it is likely that CS must cripple more than one tolerance mechanism for autoimmunity to occur.
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PMID:Cyclosporine-induced autoimmunity and immune hyperreactivity. 195 15

Syngeneic graft-versus-host disease (SGVHD) is a T cell-mediated autoimmune disease occurring postsyngeneic bone marrow transplantation and the administration of the potent immunosuppressive agent, cyclosporine A. Paradoxically, cyclosporine A disrupts the immunologic homeostasis governing self-tolerance. Our studies using an adoptive transfer model attempted to identify effector mechanisms associated with the autoimmune disease. Both CD4+ and CD8+ splenic T cells isolated from autoimmune donors were required for the adoptive transfer of active disease into lethally irradiated secondary recipients reconstituted with normal bone marrow. Doses of more than 5 x 10(6) of nylon wool depleted splenocytes from autoimmune donors effectively transferred disease into lethally irradiated secondary recipients. Splenocytes that are T cell depleted or CD4(+)-enriched cells did not elicit disease upon adoptive transfer. Nylon wool fractionated CD8+ splenocytes also failed to adoptively transfer disease unless high doses (greater than or equal to 30 x 10(6)) were used. The disease transferred with the CD8+ subset presented as acute type SGVHD and was self-limiting. The recombination of the individually isolated T cell subsets not only restored but also enhanced immune reactivity upon adoptive transfer. Moreover, use of the recombined subsets resulted in progressive disease with the development of chronic type SGVHD. The titration of each subset to the other suggested that a minimal number of CD4+ T cells was required to potentiate the CD8+ autoreactive cells in vivo. Further analysis of the helper cell involved demonstrated that it had a CD4+ CD45r- phenotype, characteristic of an amplifying helper cell population. Administration of IL-2 did not substitute for CD4+ Th cells but yet amplified the activity of unfractionated cells or recombined subsets implicating the role of other factors in the pathogenesis of SGVHD. Delineation of the effector mechanisms involved in SGVHD is critical in determining the underlying events that trigger either the production of autoreactive cells or the perturbation of the regulation of these autoreactive cells, culminating in autoimmunity.
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PMID:Effector mechanisms in cyclosporine A-induced syngeneic graft-versus-host disease. Role of CD4+ and CD8+ T lymphocyte subsets. 197 85

Lethally irradiated rats reconstituted with syngeneic bone marrow and treated for 40 or 80 days with Cyclosporin A (Cy-A) contract disease mimicking graft-versus-host disease about 3 weeks after withdrawal of the drug. We investigated the reconstitution of peripheral blood lymphocytes after this treatment. A selective effect on the regeneration of the CD4+ cells was observed. During Cy-A administration CD4(+)-cell regeneration was almost completely suppressed, but within 3 weeks after withdrawal of the drug such cells reappeared in blood and reached pre-irradiation levels about 6 weeks later. The coincidence of the reappearance of CD4+ cells and the onset of autoimmune disease suggests a causal relation between both events.
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PMID:Perturbation of T-cell differentiation in lethally irradiated rats reconstituted with syngeneic bone marrow and treated with cyclosporin-A. 251 75

The effect of a number of drugs commonly used to treat the more severe exacerbations of the autoimmune disease systemic lupus erythematosus (SLE) in humans has been investigated in the murine chronic graft-versus-host (GVH) induced model of lupus. This was undertaken in order to determine the value of this model for the investigation of immunomodulant drugs, with particular regard to the reproducibility of disease induction and methods of monitoring disease progression. The drugs were azathioprine, cyclophosphamide, cyclosporin A and dexamethasone. All of these, except for azathioprine, reduced disease severity, assessed as the development of lupus nephritis. Anti-ssDNA autoantibodies were also reduced in titre in the dexamethasone-treated group. Overall, these findings, combined with the reproducible induction of disease seen in this model, support the use of chronic GVH disease as a model for SLE and show that the induced disease can be ameliorated by drugs effective in the treatment of SLE in humans.
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PMID:Murine chronic graft-versus-host disease as a model of systemic lupus erythematosus: effect of immunosuppressive drugs on disease development. 261 55

Neopterin is a pyrazino-pyrimidine compound which is biosynthesized by macrophages. Increased concentrations of neopterin have been reported in conditions causing a stimulation of cellular immunity, such as viral and other infections, graft versus host disease, autoimmune disease and different malignancies. Recently, urinary neopterin levels have been found increased in patients with acute viral hepatitis and NANB chronic hepatitis. In the present study, neopterin serum levels have been measured in 23 cirrhotic patients (6 HBV related, and 17 cryptogenetic cirrhosis, 7 of them occurring in alcoholic subjects) and in 24 normal subjects. Mean values of serum neopterin were significantly increased in cirrhotics (3.92 +/- 3.28 ng/ml versus 1.24 +/- 0.51 ng/ml in controls, p less than 0.01). Serum neopterin values were not found to be significantly different in cirrhotics assessed in three different clinical classes according to Child's classification and in cirrhotics with and without serological findings of active disease. In fact, in cirrhotic patients, serum neopterin levels did not correlate with the values of serum AST, ALT, ALP, GGT and gamma-globulin. These data show that increased levels of serum neopterin occur in cirrhotic patients, but there is no relation between serum neopterin values and the activity or the clinical severity of the disease. The results are consistent with the hypothesis that activated macrophages are involved in all stages of liver cirrhosis irrespective of its aetiology.
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PMID:Serum neopterin levels in liver cirrhosis. 263 48


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