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)

Induction of a graft-vs-host reaction in irradiated (BALB/c X C57BL/6)F1 mice (CBF1 mice) with bone marrow cells (BMC) plus spleen cells of BALB/c mice leads to bone marrow transplantation--GVHD (BMT-GVHD). BMT-GVHD is characterized by liver disease, splenomegaly, and hypergammopathy. In addition, we found that increased serum IgE and IgG1 levels were correlated with BMT-GVHD such as liver disease and splenomegaly. The allotype of increased IgE levels in BMT-GVHD was IgEa of donor origin, not IgEb of host origin. We also found that in the thymus of murine BMT-GVHD, the CD4+ CD8+ double-positive T cells were decreased, but the CD4+ CD8- or CD4- CD8+ single-positive T cells were increased. Interestingly, double-positive T cells appeared in the spleen, suggesting that abnormal T cell differentiation existed in murine BMT-GVHD. When the recipients were treated with anti-IL-4 Ab (11B11), the increase of IgE and IgG1 was markedly reduced and liver disease and splenomegaly were also prevented. Moreover, abnormal T cell differentiation and maturation were suppressed. These observations suggest that IL-4 plays an important role in immunoregulation or pathogenesis of allogeneic effects, and 11B11 prevents immunodysfunction including T cell differentiation in the thymus or the spleen and autoimmune symptoms in murine BMT-GVHD.
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PMID:Anti-IL-4 antibody prevents graft-versus-host disease in mice after bone marrow transplantation. The IgE allotype is an important marker of graft-versus-host disease. 787 41

Twelve of 3803 consecutive marrow allograft patients treated at this center over the past 20 years have had a post-transplant tissue diagnosis of toxoplasmosis: 10 at autopsy and 2 by brain biopsy. This infection was identified in none of 509 autologous marrow recipients. Occurrence of toxoplasmosis was 0.31 cases per 100 allogeneic transplants and 1.0 per 100 autopsies. An estimated 15% of allogeneic transplant recipients were seropositive for Toxoplasma gondii and 2% of seropositive patients developed toxoplasmosis. Pre-transplant serology was positive by both dye and agglutination tests in 11 infected patients tested. Sequential IgG, IgM, IgA, IgE antibody titers to T. gondii and the differential agglutination ratio were not helpful in diagnosing toxoplasmosis. Median day of clinical presentation was day 59 post-transplant (35-97 days) and of diagnosis, day 62 after transplant (37-143 days). Eleven patients had graft-versus-host disease (GVHD) of grades II-IV. All 12 patients died. Infection was diagnosed prior to death in only 16% of patients and contributed to death in at least 40%. Histopathology revealed tachyzoites of T. gondii most prevalent in brain (100%), heart (67%) and lungs (33%), and toxoplasma cysts alone in heart (33%) and lungs (22%). Toxoplasma infection was diagnosed in two patients receiving trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia prophylaxis suggesting this was insufficient prophylaxis for toxoplasmosis. Toxoplasmosis appeared to occur by reactivation within the first 6 months after marrow transplant. Infection developed in patients who were seropositive for T. gondii pre-transplant, had received allogeneic marrow and had severe GVHD.
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PMID:Toxoplasma gondii infection in marrow transplant recipients: a 20 year experience. 805 7

A hypereosinophilic syndrome associated with dermatitis has been observed rarely in association with HIV infection. We describe the case of a young man with AIDS who came to us with a diffuse cutaneous eruption, fever, angioedema, eosinophilia, and a mildly elevated serum IgE level. No allergic or infectious cause of this illness could be determined, and the patient was treated with corticosteroids and PUVA therapy, resulting in complete resolution of the dermatitis and associated findings. In this case, there were clinical and histopathologic similarities to the idiopathic hypereosinophilic syndrome and to acute graft-versus-host disease. The serum level of the cytokine interleukin-5 (IL-5), which is associated with eosinophil production, was found to be mildly elevated during the peak of the eruption, while samples drawn previously and subsequently were not. Although it appears that the syndrome we describe is associated with the measurably elevated level of IL-5, further investigation is required to determine whether there is a cause and effect relationship between IL-5 and this entity. A brief review of the literature concerning eosinophils and HIV infection is also presented in the context of this case.
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PMID:Hypereosinophilic syndrome associated with HIV infection. Military Medical Consortium for Applied Retroviral Research. 815 85

BALB/c mice injected at birth with (BALB/c x C57BL/6)F1 hybrid spleen cells developed host versus graft disease (HVGD) with immunological features, such as various autoantibodies, immune complex nephritis, hepatosplenomegaly, and malignant lymphomas. In addition we found that the increased IgE levels correlated strongly with the histological grades or stages of the liver disease. In the sera of mice with HVGD and liver alterations, anti-smooth muscle antibodies (ASMA) and anti-nuclear antibodies (ANA) were detected. The subclass of ASMA was IgG1, whereas the subclasses of ANA were IgG1, IgG2a, and IgG2b. When the recipient BALB/c mice were injected at birth and at Day 3 in addition also with monoclonal anti-IL-4 antibody 11B11, the increase of IgE and IgG1 was markedly reduced and the liver disease was drastically prevented. These observations suggest that IL-4 plays an important role in the initiation of the immunoregulatory function or pathogenesis of the allogeneic effects and that the monoclonal anti-IL-4 antibody 11B11 prevents the immunodysfunctions and the autoimmune hepatopathy in mice with HVGD. The increased IgE level in the serum is a good marker of HVGD.
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PMID:Increased IgE level as a marker of host-versus-graft disease: inhibition of this HVGD with a monoclonal antibody to IL-4. 851 6

Omenn syndrome is a variant of SCID, inherited as an autosomal recessive disorder, and characterized by severe eczematoid dermatitis, eosinophilia, elevated serum IgE and a distinctive histology in enlarged lymph nodes. The etiology of Omenn syndrome is unknown, however, unlike other forms of SCID; patients with Omenn syndrome have activated T lymphocytes in their circulation capable of non-MHC restricted cytotoxic function. Recently, it has been observed that the use of immunosuppressive therapy, particularly cyclosporine, can modify the clinical manifestations of the disorder. Prior to the use of bone marrow transplantation this disease was universally fatal. Death typically occurred in infancy as the result of opportunistic infections and/or malignancies, most notably lymphomas. While bone marrow transplantation has become quite successful for many phenotypes of SCID, even with the use of alternative donors other than histocompatible siblings, in Omenn syndrome it remains a challenge. In our experience, patients with Omenn syndrome exhibit a higher incidence of Gram negative sepsis, before and during transplantation, and carry a significant risk of post-transplant rejection when compared with patients with other phenotypes of SCID. We report the results of six patients treated with bone marrow transplantation from alternative donors, three had unrelated donors (URD) and three had haplo-identical parental donors. Five of the six patients achieved complete and/or durable donor cell engraftment and only one patient experienced acute GVHD. Three patients died of transplant-related complications (infection or EBV-associated B cell lymphoma) between day +22 and day +95 post-transplant. Three patients survived more than 1 year post-transplant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mismatched bone marrow transplantation for Omenn syndrome: a variant of severe combined immunodeficiency. 853 10

Isotype- and allotype-specific IgE determinations by sandwich ELISA with monoclonal antibodies to Igh-7 (6HD5, HMK-12), Igh-7a (No. 297) and Igh-7b /JKS-6) were used to qualitate antibodies of the IgE class. The sensitivity of the method is 0.1 ng/ml. Serum IgE levels were much higher in mice infected with Nippostrongylus brasiliensis. In sera of BALB/c, AKR and C3H/JCL mice only IgEa, in sera of C57BL/6 and CB-20 only IgEb, in sera of (BALB/c x C57BL/6) F1 mice, both allotypes were detected, as expected. In mice with autoimmune diseases, such as NZB, NZW, (NZB x NZW) F1, MRL/Ipr and MRL/n strains which all belong to the IgEa allotype group, IgE and IgEa were very high. In the sera of BXSB mice, both IgEa and IgEb were detected. Both IgEa and IgEb from donor and host were increased in the sera of mice with graft-versus-host disease after transplantation but only the IgEa (from the donor) was increased in mice with graft-versus-host disease after bone marrow transplantation. In the former, both B cells (from donor and host) secreted IgE, whereas in the latter only the donor cells did. These are the first observations showing the importance of IgE allotype secretion as an indication of graf-versus-host disease.
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PMID:IgE allotypes in sera of mice with autoimmune diseases and in mice with graft-versus-host disease after transfusion or bone marrow transplantation. 885 23

We have determined the capacity of donor CD4 and CD8 T cells to mediate liver injury in the B10.D2 (donor) into BALB/c (host) chronic graft-versus-host disease (GVHD) model. First, we compared the effects of treating GVHD mice with anti-CD4 or anti-CD8 versus no treatment on the liver histology scores and elevated serum IgE levels in this model. We also examined the abilities of purified donor total T, CD4, and CD8 cells to mediate hepatic GVHD lesions. Anti-CD4 and anti-CD8 treatments caused profound depletion of peripheral CD4+ and CD8+ cells, respectively, and produced a relative enrichment of the CD8+ and CD4+ cells in the liver. Hepatic GVHD lesions and elevated serum IgE concentrations were both suppressed by anti-CD4 treatment. Anti-CD8 treatment had no effect on the severity of hepatic lesions and caused a significant increase in serum IgE levels. Attempts to induce hepatic GVHD with purified donor CD4 and CD8 cells were inconclusive because the onset of liver lesions was delayed and the lesions in both groups were contaminated by the opposite subset. Altogether, our results indicate that both hepatic lesions and elevated serum IgE concentrations in this GVHD model are dependent on donor CD4 cells. Donor CD4 cells mediated hepatic GVHD in the absence of CD8 cells. Donor CD8 cells did not produce hepatic GVHD in the absence of CD4 cells and appeared to be dependent on CD4 cells.
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PMID:Contributions of donor CD4 and CD8 cells to liver injury during murine graft-versus-host disease. 897 Jun 18

Significant increases in serum levels of IgE have often been observed in allogeneic bone marrow transplantation patients and have generally been thought to be diagnostic of graft-versus-host disease (GVHD), rather than an agent involved in the pathogenesis of the disease. Experimental murine GVHD models have also indicated associations of hyper-IgE activity, yet the role of IgE in GVHD pathogenesis has never been tested directly. In the current study, we have tried to address this issue by using recently developed peptide analog antagonists for the interaction of IgE with the Fc epsilon RI receptor, which is necessary for triggering mast cells and other cell types when cross-linked by antigens. A synthetic cyclized 13-amino acid peptide was previously designed from the modeled C-C' loop region of the Fc epsilon RI alpha-chain and was found to act as a competitive inhibitor of IgE-Fc epsilon RI alpha binding. The peptide was generated in two forms, a cyclic L-(L-IgEtide) and retro D-amino acid composition (rDIgEtide), the latter to increase resistance to protease degradation for in vivo applications. These two inhibitor peptides were then used to test the hypothesis that IgE could be involved in the pathogenesis of acute GVHD, in the B10.D2-->DBA/2 (900 cGy) strain combination, with GVHD directed to minor histocompatibility antigens. Both peptides demonstrated significant inhibition of the development of lethal GVHD, supporting the involvement of IgE at some level of disease pathogenesis.
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PMID:Peptide analogs that inhibit IgE-Fc epsilon RI alpha interactions ameliorate the development of lethal graft-versus-host disease. 936 Jul 80

The effects of chloroform extract of Tripterygium Wilfordii Hook f (TWH extract) on chronic graft-versus-host disease (GVHD) were examined in a murine experimental model. Chronic GVHD was induced by intravenous transfer of parental DBA/2 spleen cells into unirradiated (C57BL/6 x DBA/2)F1 recipient mice. The effects of TWH extract on GVHD were assessed by measuring both the degree of splenomegaly and the total serum IgE levels 3 weeks after the cell transfer. Subcutaneous administration of TWH extract once a day for 3 weeks suppressed chronic GVHD in a dose-dependent manner. Significant suppression of splenomegaly was first noted in mice treated with 7.5 micrograms/kg of the agent. The maximum inhibition was observed when mice were treated with more than 10.0 micrograms/kg (but not 5.0 micrograms/kg) caused complete suppression of serum IgE hyperproduction. The ability of donor T cells purified from recipient spleen cells to produce interleukin 4 in response to stimulation with anti-CD3 monoclonal antibody was significantly abrogated when recipient mice were treated with 10.0 micrograms/kg of the agent. These results strongly suggest that TWH extract will be an addition to the cohort of immunosuppressive therapies used in solid organ and bone marrow transplantation.
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PMID:Inhibition of murine chronic graft-versus-host disease by the chloroform extract of Tripterygium wilfordii Hook f. 950 54

The use of inbred mouse strains of defined genetic background has allowed for the development of systems capable of reproducibly generating either an acute or chronic graft-versus-host disease (GvHD). The malononitrilamides MNA 279 and MNA 715, analogues of the main metabolite of leflunomide, have been shown to directly inhibit T-cell proliferation and B-cell functions. Therefore, they have been studied in a local GvH reaction in the popliteal lymph node (PLN) assay in LBN rats, on the development of an acute and lethal GvHD in B6C3F1 mice and on a chronic autoimmune GvHD in BDF1 hybrid mice. In the PLN assay an oral administration of various concentrations (7.5 to 50 mg/kg) of both MNAs inhibited the localized GvH reaction dose-dependently and suppressed the lymph node hyperplasia. Both MNAs also acted therapeutically in this assay when they were given as late as day 4 or 5 after challenge. In the model of an acute lethal GvHD the treatment of the GvH-B6C3F1 hybrid mice with the MNAs (2.5 to 20 mg/kg/day) shortly after disease induction on days 3 to 12 resulted in a dose-dependently improved survival rate. With 20 mg/kg of drugs, mortality of this life-threatening GvHD was completely prevented and also other parameters like splenomegaly, erythrocyte counts and hematocrit values were strongly suppressed. Treatment of sensitized GvH-BDF1 hybrid mice in the chronic autoimmune-like model with the MNAs (30 mg/kg/day), given on days 3 to 36 by oral gavage, resulted in an improved survival rate, inhibited lymphadenopathy and splenomegaly, reduced the levels of autoantibodies and other immunoglobulins like IgE and IgG1, prevented proteinuria and the development of glomerulonephritis. Both MNA 279 and MNA 715 can inhibit ongoing aberrant immune responses in animals suffering from GvHD.
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PMID:The new immunosuppressants, the malononitrilamides MNA 279 and MNA 715, inhibit various graft-vs.-host diseases (GvHD) in rodents. 951 26


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