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

A patient with acute lymphoblastic leukaemia in first remission received a bone marrow transplant from his HLA-identical brother. The patient had a remote history of asthma and the bone marrow donor had allergic asthma. The patient developed acute graft-versus-host disease and died 2 months after transplantation. At autopsy there were high numbers of plasma cells in lymphoid tissues. The majority of this cell population was of polytypic IgG, IgM or IgA origin, but there was a significant contribution by monotypic IgE-lambda-containing cells, varying from 10% in the appendix to 35% in lymph node. The serum IgE level in the patient was less than 0.5 IU/ml before transplantation, and 8.5 IU/ml 1 month thereafter. In the donor the value was about 400 IU/ml. In the donor only, specific IgE antibodies to various allergens were detectable. The bone marrow of the donor contained 0.4% plasma cells, of which 36% were IgE positive (chi/lambda ratio 1/11). These findings are compatible with literature data on elevations in serum IgE level following bone marrow transplantation. We suggest that the IgE-lambda plasma cell population is of donor origin.
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PMID:Monotypic immunoglobulin E plasma cells in an allogeneic bone marrow transplant recipient. 353 16

A 39 year old patient diagnosed of severe aplastic anemia and treated with allogenic bone marrow transplantation and who presented chronic eosinophilic pneumonia eight months after the transplant is presented. The patient had no previous history of asthma or atopy. Conditioning was performed with cyclophosphamide and total body irradiation. Prophylaxis of the graft versus host disease was carried out with cyclosporin and short course of methotrexate. At day 30 mild graft versus host disease appeared which spontaneously resolved. A progressive increase in the number of eosinophils was observed from day +40 reaching 1.05 x 10(9)/l at day +180 coinciding with suspension of the cyclosporine. The patient remained asymptomatic with no evidence of chronic graft versus host disease. At 8 months following allogenic transplantation the patient developed three episodes of fever, cough, moderate dyspnea and pulmonary infiltrates. Respiratory tests showed a restrictive pattern. Bronchoalveolar lavage contained 20% of eosinophils. Upon lung biopsy alveolar infiltration by eosinophils, lymphocytes and mononuclear cells was observed. Diagnosis of chronic eosinophilic pneumonia was made with initiation of steroid treatment. A drastic response was observed. The patient remained asymptomatic without recurrence and without evidence of chronic graft versus host disease. This picture may have been caused by the donor eosinophils given that retrospective evaluation demonstrated a persistent moderate eosinophilia in the donor.
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PMID:[Chronic eosinophilic pneumonia in a patient treated with allogenic bone marrow transplantation]. 820 96

Although eosinophil infiltrate has been recognized in hepatic graft-versus-host disease, its significance in relation to hepatic graft-versus-host disease lesions is unknown. In the present study, we analyzed hepatic eosinophil infiltration in relation to bile duct damage in experimental mouse graft-versus-host disease across minor histocompatibility barriers up to 14 months after transplantation. Portal eosinophil infiltration was found from 1 week after transplantation throughout the entire 14-month observation period. It was most striking during the early chronic stage of hepatic graft-versus-host disease between 2 to 7 months, with a peak at 5 months after transplantation. Microscopic and electron microscopic study revealed eosinophils infiltrated around the bile duct as well as in the bile duct epithelial layer. They were commonly found together with lymphocytes but were also occasionally found singly around the bile duct and in the bile duct epithelial layer. Bile duct epithelial cells in contact with and in the vicinity of eosinophils showed a variety of generative changes, occasionally associated with the presence of extracellular eosinophil granules. Bile duct epithelial cells with eosinophil infiltration just beneath the basement membrane frequently showed further characteristic severe degenerative changes with shedding or dropping-off into the lumen, which features were quite similar to those seen in the bronchial epithelium in asthma patients. These results indicate that not only lymphocytes but also eosinophils may be involved in the production of the bile duct injury in hepatic graft-versus-host disease, especially in its early chronic stage.
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PMID:Histological changes of the liver in experimental graft-versus-host disease across minor histocompatibility barriers. VIII. Role of eosinophil infiltration. 886 77

Mosmann first proposed the existence of subsets of CD4+ T cells that produce distinct types of cytokines. Native T lymphocytes (Thp cells) differentiates into either CD4+ Th1 cells that produce IL-2, IFN gamma, and lymphotoxin which promote cell-mediated immunity, or into Th2 cells that produce IL-4, IL-5, IL-6, IL-10 and IL-13, which promote antibody production and humoral immunity. These T cell subsets reciprocally regulate one another since one of the Th1 products, IFN gamma, inhibits the proliferation and functions of Th2 cells, whereas the Th2 products, IL-4 and IL-10, suppress cytokine production by Th1 cells. A distinct Th1/Th2 divergence determine resistance versus susceptibility to diseases such as leishmaniasis and toxoplasmosis in mice. In allergic diseases such as atopic dermatitis and allergic asthma, allergen-specific T cells acquired the Th2 phenotype. These Th2 cells produce IL-4, IL-5, IL-6, IL-10 and IL-13. These cytokines induce eosinophilia and an Ig class switch to IgG4 and IgE. These Th2 cells are responsible for the enhanced production of IgE antibodies. These findings indicate that Th2 cytokines play an important role in the development of allergic diseases. The importance of cell-mediated immunity, particularly donor-anti-host CTL, in mediating acute GVHD suggests that Th1 cytokines may be important in the induction of acute GVHD. To further characterize the roles of Th1 and Th2 cytokines in the development of acute GVHD, analysis of IL-2, IFN gamma, IL-4 and IL-10 cytokine genes was performed by RT-PCR on biopsied skin specimen. An increase in mRNA expression for IL-2 and IFN gamma was observed, whereas there was no significant increase in IL-4 and IL-10 mRNA. These data suggest that Th1 cytokines may be essential for the development of acute GVHD. It is apparent that Th1 cytokines are generally harmful to the maintenance of pregnancy. We have shown that Th2 cytokines are produced by maternal T lymphocytes at the maternal-fetal surface (retroplacental blood lymphocytes). This finding strengthens the hypothesis of a significant contribution of Th2 cytokines to a successful pregnancy.
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PMID:[A role for T-helper type 1 and type 2 cytokines in the pathogenesis of various human diseases]. 980 Apr 77

Increasing numbers of patients are surviving after allogeneic haematopoietic stem cell transplantation (SCT). Among these patients, a number of late complications have been described but few data on the risk factors of these long-term effects of SCT are available. We report the analysis on 105 adult patients, surviving free of haematological disease at a median time of 15 months after SCT. At the time of screening, 52% had returned to work, general health status was normal in 67% and 47% were sexually active. Female patient gender odds ratio (OR) 2.9 (P = 0.01) and age > 25 years (OR = 3.2, P = 0.02) were associated with non-return to work. Decreased general status was associated with chronic graft-versus-host disease (GvHD) (OR = 3.2, P = 0.009) and irradiation (OR = 3.6, P = 0.004). Sexual inactivity was associated with younger age (OR = 7.0, P = 0.0002) and chronic GvHD (OR = 3.3, P = 0.006). Risk factors for altered pulmonary function tests included previous smoking habits, irradiation and chronic GvHD. Obstructive lung disease was associated with a previous history of asthma. Sicca syndrome and conjunctivitis were increased in patients with previous acute GvHD and cataracts were less frequent in patients with aplastic anaemia. Persistent impaired hair re-growth was less frequent in patients who received irradiation (OR = 0.18, P = 0.002) but increased in patients with previous acute GvHD (OR = 5.3, P = 0.007). Microalbuminuria was more frequent in irradiated patients (OR = 9.4, P = 0.05). Raised cholesterol was associated with age (OR = 20.8, P < 0.001), previous acute GvHD (OR = 4.7, P = 0.03), steroid use (OR = 6.3, P = 0.001) and familial hypercholesterolaemia (OR = 4.4, P = 0.04). Decreased bone density was associated with chronic GvHD (OR = 3.9, P = 0.001). Thus, using routine tests in adult patients we were able to detect significant numbers of-non-symptomatic complications enabling early treatment.
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PMID:Health and functional status of adult recipients 1 year after allogeneic haematopoietic stem cell transplantation. 1132 2

An understanding of the factors that place the post-transplant patient at increased risk for sinusitis would help identify patients likely to develop disease and possibly allow for interventions that would decrease the incidence or severity of sinus disease. This retrospective study investigates the ability of screening paranasal sinus computed tomographic scans (CTs), clinical history, and potential risk factors for sinusitis, including history of tobacco use, history of allergies or asthma, IgG level, history of sinusitis, remission status and acute graft-versus-host disease (GVHD) to predict post-transplant sinusitis. Medical records and sinus CTs of 100 allogeneic bone marrow recipients were reviewed. There was no increased risk of developing sinusitis post SCT for patients with significant disease on screening CT, symptoms at time of transplant, a history of tobacco use, asthma or allergies, low IgG level, history of sinusitis or for patients at high risk of relapse. Patients with GVHD were 4.3 times more likely than patients without GVHD to develop sinusitis post transplant (95% CI: 1.7-11.0, P = 0.002). Acute GVHD places patients at greater risk of developing sinus infections.
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PMID:Risk factors for post-stem cell transplant sinusitis. 1185 99

Adverse reactions to iodinated contrast media are varied and known to develop in patients with asthma and a history of allergy. We describe three successful allogeneic bone marrow transplantation (BMT) patients, who all developed dermal graft-versus-host disease (GVHD) after receiving contrast media. Cutaneous GVHD triggered by contrast media has not been reported to date and has implications for the assessment, monitoring and treatment of patients during the post-transplant period.
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PMID:Contrast media triggering cutaneous graft-versus-host disease. 1208 Mar 54

Fibroblasts play a sentinel role in asthmatic disease. They are the main constituents of connective tissue and are increased in number in the asthmatic lung. They are also capable of secreting a diverse repertoire of cytokines and are able to be activated by pro-inflammatory cytokines and cell-cell contact. Previously we have reported that normal human lung fibroblasts (NHLF) can be activated by monocytes (U937) through cell-cell contact to produce GM-CSF. Here we show that GM-CSF production from NHLF activated by monocyte contact is inhibited by prednisone, a synthetic glucocorticoid used in the treatment of asthma. GM-CSF is an acidic glycoprotein that potentiates development of cells in the granulocyte and macrophage lineage and is secreted at sites of peripheral inflammation. The receptor for GM-CSF was found on NHLF by flow cytometry and was able to be up-regulated by interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha and recombinant human (rh) GM-CSF. To test autocrine effects of GM-CSF on fibroblasts, rh GM-CSF was used in proliferation studies and was found to decrease fibroblast proliferation. Prednisone was used to block NF-kappaB activation and GM-CSF gene expression as well. These data indicate mechanism of action and treatment for cell-cell contact mediated inflammation of infiltrating monocytes with fibroblasts as seen in asthma and other diseases like graft versus host disease.
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PMID:Inhibition of GM-CSF production in fibroblast-monocyte coculture by prednisone and effects of rhGM-CSF on human lung fibroblasts. 1476 71

Immunex is carrying out worldwide phase II trials on a genetically-engineered soluble interleukin-4 receptor (IL-4R, Nuvance), administered as a nebulized liquid, for the potential treatment of allergic asthma. IL-4R may also be of use in the treatment of organ transplant rejection, graft versus host disease, allergy and infectious disease.
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PMID:Nuvance (Immunex). 1615 48

Recent advances in our (patho)physiological understanding have underpinned the frequent involvement of the protein family of selectins in the progression of serious illnesses, including cancer and cancer metastasis, and immunological diseases, such as asthma, allergy and autoimmune reactions. Moreover, selectins seem to have a role in post-ischemic damage and during transplant failures (e.g. in graft-versus-host disease). Although the interplay between selectins and their counter-receptors and ligands is not always primarily involved in the development of these pathological conditions, selectins have been investigated as potential therapeutic targets for therapeutic intervention. This review focuses on the latest trends and developments in anti-selectin antibodies, anti-selectin receptor antibodies, recombinant selectin counter-receptors, low molecular weight selectin antagonists (glycomimetics), induction of selectin tolerance and selectin-targeted imaging agents.
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PMID:Selectins--potential pharmacological targets? 1705 14


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