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)

It has been reported that autoimmunity might be sometimes transferred from a donor to a recipient following allogenic bone marrow transplantation (allo-BMT). We report a patient to whom Basedow disease was transferred from the donor through an allo-BMT. A 18-year-old man with acute lymphoblastic leukemia, received the allo-BMT from his HLA-identical sister. Two-years later, he developed symptoms of palpitations and general fatigue. He was diagnosed as having Basedow disease because of hyperthyroidism, and high levels of the anti-thyroid stimulating hormone receptor antibody and antithyroid antibody. When he received the allo-BMT, his donor had neither the clinical symptoms of Basedow disease, nor abnormal findings on examination to determine her eligibility as a the donor. We retrospectively assayed anti-thyroid antibodies from their cryopreserved sera, and found the donor's anti-thyroid antibody was positive, while her serum was negative before transplantation. It was apparent that the donor had subclinical Basedow disease. The patient has remained in complete remission without any signs of chronic graft-versus-host disease (GVHD) up till the time of writing. It is believed that an anti-thyroid tissue reactive B-cell clone was transferred from the donor to the patient and commenced to produce antibodies. It is suggested that thorough investigation of the donor's autoimmunity is needed before allo-BMT. If the recipient develops an autoimmune disease after allo-BMT, we should definitely investigate the donor's autoimmunity.
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PMID:[Basedow disease occurring after allogeneic bone marrow transplantation for acute lymphoblastic leukemia]. 1241 87

Alfa-Galactosyl Ceramide was isolated from Ocean sponge which has antitumor effect against several tumors in in vivo animal model with no cytotoxicity. KRN7000(KRN) is the most potent alpha-Galactosyl Ceramide modified from the one isolated from Ocean sponge. KRN is also active against metastatic tumors through the activation ofanimal immune system. Research efforts in learning the mechanism of action, we found the important role of dendritic cells(DC) and NKT cells. NKT cells was first characterized in 1988 which is overlap some part with NK cells and T-Cells and majority is different from NK and T. KRN is active through the activation of DC and NKT in giving antigen specific immune stimulation in animal. This antigen specific stimulation is memorized by immune system and can reject second tumor challenge. KRN is not active in nude mice and NKT deficient animal. NKT cells level in blood is lower in patients with autoimmune disease, cancer, HIV positive or aplastic anemia. NKT rapidly releases IL-4 and IFN-gamma at high level when activated. NKT is CD1d and TCR restricted. NKT plays important role in autoimmune disease such as Type 1 Diabetes, Scleroderma and Systemic Lupus Erythematosus, infections such as Mycobacteria, Listeria and Malaria, GVHD control and tumor rejection. NKT acts as double edge sword, aggressive and suppressive ways. KRN can prevent the onset of Type 1 Diabetes, inhibit replication of hepatitis virus B in liver and suppress malaria replication in activating NKT cells. KRN can activate NKT through DC and activated NKT activates NK, T and macrophage. KRN also expands NKT cells and expanded NKT has full function. Although the exact role of DC and NKT is not clear, KRN clinical study results in conjunction with DC and NKT cell activation are expected.
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PMID:Role of NKT cells and alpha-galactosyl ceramide. 1243 Aug 64

To determine the role of allogeneic, autologous and syngeneic hemopoietic stem cell transplantation (SCTx) as a treatment for severe autoimmune disease (AID) we performed a literature search employing Medline, Cancer Lit and abstract books for reports on transplants for blood disorders and a concomitant AID. All reviews, case reports and abstracts available between June 1977 and September 2001 were used and attempts made to update them by e-mail by the corresponding authors. Disease-free survival (DFS) after allogeneic SCTx for 23 patients with severe aplastic anemia was 78% at 16 years and survival in unmaintained remission of concomitant AID was 64% at 13 years. DFS after allogeneic SCTx for 24 patients with hematologic malignancies was 87% at 15 years and survival in unmaintained remission for concomitant AID was 70% at 11 years. DFS after autologous SCTx for 24 patients with hematologic malignancies was 48% at 6 years and survival in unmaintained remission for concomitant AID was 29% at 3 years. Among 30 patients given allogeneic SCTx 19 developed graft-versus-host disease (GVHD) and 11 did not. Upon clinically justified discontinuation of all immunosuppressive therapy, 3/11 patients without GVHD relapsed with their concomitant AID (freedom of AID-relapse 69% at 9 years), whereas none of 19 patients with GVHD did so (log rank: P = 0.0135). Freedom of AID-relapse was superior after allo SCTx compared to autologous SCTx (89% at 18 years vs 38% at 5 years; log rank: P = 0.0002). Our data suggest that a graft-versus-autoimmunity effect after allogeneic hemopoietic SCTx mediates elimination of autoimmunity.
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PMID:Clinically demonstrable anti-autoimmunity mediated by allogeneic immune cells favorably affects outcome after stem cell transplantation in human autoimmune diseases. 1243 98

Animal models with impaired thymic negative selection do not always cause autoimmune diseases despite the development of an autoreactive T-cell repertoire. We investigated the requirements for the development of systemic autoimmune disease by using bone marrow chimeras that lacked expression of major histocompatibility complex (MHC) class II on thymic antigen-presenting cells (APCs), leading to impaired negative selection. We found that impaired negative selection mediated by absence of MHC class II, but not MHC class I, permitted the development of systemic autoimmune disease that is indistinguishable from acute graft-versus-host disease (GVHD). Thymectomy prevented disease, confirming the causal association of the thymus with its development. Adoptive transfer of CD4+ T cells caused GVHD in secondary hosts only when they were irradiated, and cotransfer of peripheral CD4+ and CD8+ T cells from naive mice prevented the disease. These results demonstrate that impaired thymic negative selection can cause lethal autoimmune disease indistinguishable from acute GVHD in the context of a proinflammatory milieu when peripheral regulatory mechanisms are absent.
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PMID:Impaired thymic negative selection causes autoimmune graft-versus-host disease. 1266 38

Inorganic mercury (iHg) is known to induce autoimmune disease in susceptible rodent strains. Additionally, in inbred strains of mice prone to autoimmune disease, iHg can accelerate and exacerbate disease manifestations. Despite these well-known links between iHg and autoimmunity in animal models, no association between iHg alone and autoimmune disease in humans has been documented. However, it is possible that low-level iHg exposure can interact with disease triggers to enhance disease expression or susceptibility. To address whether exposure to iHg can alter the course of subsequent acquired autoimmune disease, we used a murine model of acquired autoimmunity, lupus-like chronic graft-versus-host disease (GVHD), in which autoimmunity is induced using normal, nonautoimmune prone donor and F1 recipient mice resistant to Hg-induced autoimmunity. Our results indicate that a 2-week exposure to low-dose iHg (20 or 200 micro g/kg every other day) to donor and host mice ending 1 week before GVHD induction can significantly worsen parameters of disease severity, resulting in premature mortality. iHg pretreatment clearly worsened chronic lupus-like disease, rather than GVHD worsening iHg immunotoxicity. These results are consistent with the hypothesis that low-level, nontoxic iHg preexposure may interact with other risk factors, genetic or acquired, to promote subsequent autoimmune disease development.
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PMID:Low-dose exposure to inorganic mercury accelerates disease and mortality in acquired murine lupus. 1289 45

A 38-year-old woman with agnogenic myeloid metaplasia complicated by the poor prognostic factors of severe osteosclerosis, prominent hepatosplenomegaly, and profound anemia was treated with FLAG chemotherapy to decrease her organomegaly before undergoing a nonmyeloablative allogeneic stem cell transplant from a matched-sibling donor. The patient's pre- and post transplant course were complicated by an autoimmune disorder and her post transplant course was complicated by severe hepatic and gastrointestinal GVHD. A technetium-99m sulfur colloid scan 4 months post transplant and bone marrow studies 8 months post transplant demonstrated intramedullary hematopoiesis, complete resolution of marrow fibrosis, and partial resolution of osteosclerosis.
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PMID:FLAG chemotherapy followed by allogeneic stem cell transplant using nonmyeloablative conditioning induces regression of myelofibrosis with myeloid metaplasia. 1295 30

Graft versus host disease is a significant cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Galectin-1, a mammalian lectin that modulates T cell function and apoptosis, has been shown to be immunomodulatory in animal models of autoimmune disease. We investigated the efficacy of galectin-1 in a murine model of graft versus host disease and found that 68% of galectin-1-treated mice survived, compared to 3% of vehicle-treated mice. Galectin-1-treated animals also had reduced inflammatory infiltrates in tissues compared to animals treated with vehicle alone. Galectin-1 did not affect engraftment of donor hematopoietic cells. However, galectin-1-treated animals demonstrated increased cellularity in bone marrow and spleen with increased numbers of splenic B cells and CD4 T cells compared to those animals treated with vehicle alone. Galectin-1 treatment also significantly improved reconstitution of normal splenic architecture following transplant. Production of type I cytokines interleukin-2 (IL-2) and interferon-gamma was reduced in splenocytes derived from galectin-1-treated transplanted mice when compared to animals treated with vehicle alone, while production of the type II cytokines, IL-4 and IL-10, was similar between the two groups of animals. Although splenocytes from galectin-1-treated transplanted animals responded to both third party antigens and leukemic challenge, host alloreactivity was significantly reduced when compared to cells from vehicle-treated animals. These results demonstrate that galectin-1 therapy is capable of increasing survival and suppressing the graft versus host immune response without compromising engraftment or immune reconstitution following allogeneic hematopoietic stem cell transplant.
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PMID:Amelioration of graft versus host disease by galectin-1. 1469 44

Photopheresis (extracorporeal photochemotherapy) is an immunomodulatory therapy that entails the reinfusion of peripheral blood mononuclear cells after exposure to the photoreactive agent methoxsalen and ultraviolet A (UVA) radiation. Currently available at approximately 150 treatment centers worldwide, photopheresis is approved by the US FDA for advanced-stage cutaneous T-cell lymphoma (CTCL) and has also shown promise in treating nonmalignant immune-related conditions such as organ transplant rejection, acute and chronic graft-versus-host disease, and autoimmune disorders. The precise mechanism by which photopheresis evokes clinical responses is unknown, although this modality seems capable of modulating T-cell and monocyte activity. Clinical and laboratory findings suggest that the reinfusion of peripheral blood mononuclear cells after exposure to UVA-activated methoxsalen engenders an immune response against proliferating T-cell clones. Methoxsalen is a naturally occurring furocoumarin that is biologically inert until exposed to UVA radiation at the proper wavelength, at which time it irreversibly cross-links DNA thymine bases and arrests cell proliferation. T cells isolated from the peripheral blood of patients after photopheresis demonstrate significantly increased levels of apoptosis, whereas macrophages and dendritic cells exhibit the ability to phagocytize the apoptotic T cells. It is surmised that photopheresis enhances the uptake, processing, and presentation of distinctive antigens from apoptotic pathogenic T cells by macrophages and dendritic cells leading to the induction of an anticlonotypic response by cytotoxic T cells. Induction by photopheresis of apparently opposite immune processes (i.e. upregulation of an antitumor response and downregulation of allogeneic or autoimmune responses) can be explained by its ability to target either a single malignant T-cell clone (as in CTCL) or multiple activated T-cell clones (as in organ transplant rejection, graft-versus-host disease, or autoimmune disease). Because acute inflammation and T-cell activation may be important in the pathogenesis of restenosis following percutaneous transluminal coronary angioplasty (PTCA), photopheresis was used for the first time at our center to prevent restenosis. A total of 78 patients with single-vessel coronary artery disease amenable to PTCA with or without stent deployment were enrolled, 41 in the control group and 37 in the photopheresis group. Clinical restenosis occurred in significantly less photopheresis patients than control patients (8 vs 27%; p = 0.04), with a relative risk of 0.30 (95% confidence interval, 0.09-1.00). A multicenter clinical trial following a US FDA-recommended protocol is currently underway to better determine what, if any, impact photopheresis has in preventing restenosis.
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PMID:Photopheresis. Therapeutic potential in preventing restenosis after percutaneous transluminal coronary angioplasty. 1472 45

CD40 signaling has been implicated in various pathogenic processes such as chronic inflammatory disease, graft-versus-host disease, autoimmune disease and cancer. We previously demonstrated in an in vitro system that the CD40/CD40L pathway mediates late interleukin (IL) 12 production in response to Cryptococcus neoformans. The purpose of this study was to examine the course of C. neoformans infection in the absence of CD40/CD40L costimulation. We compared infection in mice genetically lacking CD40L (CD40L(-/-)) and in the wild-type counterpart. The animals were injected intratracheally with C. neoformans and monitored for clearance of the organism and the development of cellular immune response. CD40L(-/-) mice exhibited an exacerbation of infection, evaluated as scarce inflammatory response in the lung, that mirrored an increase of fungal burden. This correlated with impairment of nitrite production and antimicrobial activity by macrophages against C. neoformans and unrelated microorganisms such as Candida albicans. Moreover, IL-12 production by splenic macrophages was diminished in CD40L(-/-) mice and interferon-gamma production by CD4 and CD8 T cells was decreased. CD4 T cells retained the ability to express a costimulatory molecule, CTLA-4, but showed a decrease in CD28 expression. This latter molecule is implicated in a positive effect on proliferation, cytokine production and survival of T cells. Collectively these data demonstrate that absence of CD40L correlates with (i) reduced antimicrobial activity of natural effector cells; (ii) reduction of the magnitude of T cell response; and (iii) increase of fungal growth in the brain. These findings suggest that disruption of CD40/CD40L may be deleterious for development of an efficient immune response to C. neoformans and may identify potential molecular targets for novel immunotherapeutic approaches
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PMID:Disruption of CD40/CD40L interaction influences the course of Cryptococcus neoformans infection. 1473 88

The development of malignant disease might be seen as a failure of immune surveillance. However, not all tumors are naturally immunogenic, and even among those that are immunogenic, the uncontrolled rapid growth of a tumor may sometimes out-run a robust immune response. Nevertheless, recent evidence suggests that mechanisms of tolerance that normally exist to prevent autoimmune disease may also preclude the development of an adequate antitumor response and that tumors themselves have the ability to thwart the development of effective immune responses against their antigens. A major challenge has been to develop approaches to breaking this tolerance in tumor-bearing hosts, and recent advances in our understanding of antigen presentation and tolerance have led to some promising strategies. An alternative approach is to use T cells from nontumor-bearing, allogeneic hosts in the form of lymphocyte infusions, with or without hematopoietic cell transplantation. Immunotherapy may occur in this setting via the response of nontolerant, tumor antigen-specific T cells from nontumor-bearing hosts or via the powerful destructive effect of an alloresponse directed against antigens shared by malignant cells in the recipient. Approaches to exploiting this beneficial effect without the deleterious consequence of graft-versus-host disease in allogeneic hematopoietic cell recipients are discussed.
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PMID:Tolerance and cancer: mechanisms of tumor evasion and strategies for breaking tolerance. 1502 Jun 16


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