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)

We report the immunological characteristics of five patients with Omenn's syndrome, a rare inherited immunodeficiency also known as combined immunodeficiency with hypereosinophilia. The syndrome is characterized by T cell infiltration of skin, gut, liver, and spleen leading to diffuse erythroderma, protracted diarrhea, failure to thrive, and hepatosplenomegaly. Blood T cells as well as those infiltrating the skin and gut were found to express activation markers and were partially activated by mitogens but not by antigens. Although the lesions resembled those in graft-versus-host disease, the blood T cells were shown by DNA haplotype analysis using probes revealing variable number of tandem repeats to belong to the patients as well as the T cells infiltrating the gut and skin in one patient. A given T cell subset (TCR alpha beta+, CD4+/CD8+, or TCR gamma delta+) was predominant in each patient, with a specific distribution in the skin lesions. Moreover, the study of T cell receptor beta, gamma, and delta gene rearrangements in four patients revealed oligoclonality involving C beta 1, C beta 2, or different V gamma J gamma or V delta J delta genes. This indicates that restricted heterogeneity of the T cell repertoire, previously reported in one case, is a major feature of this syndrome. The occurrence of alymphocytosis-type severe combined immunodeficiency in the brother of one of the patients suggests that the restricted heterogeneity of T cell receptor gene usage in Omenn's syndrome may arise from leakiness, within the context of a genetically determined faulty T cell differentiation.
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PMID:Restricted heterogeneity of T lymphocytes in combined immunodeficiency with hypereosinophilia (Omenn's syndrome). 201 May 48

Highly purified and cloned preparations of interleukin-1 (IL-1) were found to antagonize the capacity of erythropoietin (Epo) to stimulate the proliferation of mouse spleen and bone marrow erythroid precursor cells (EPC) in culture. Cloned murine IL-1 and purified and cloned human IL-1 alpha and IL-1 beta were approximately equipotent in this assay. IL-1 inhibited the proliferation response of EPC even when added as long as 17 h after Epo, suggesting that IL-1 does not affect binding of Epo to receptors or biochemical events following shortly thereafter. Indomethacin did not influence the inhibitory effect of IL-1 on Epo-induced proliferation, and PGE2 had no demonstrable effect on the process. Tumor-necrosis factor-alpha and interferons beta 1, and gamma did not affect Epo-induced proliferation. It is suggested that IL-1 mediated antagonism of the effects of Epo on erythroid precursors is a factor in the pathogenesis of many types of hypoplastic anaemia, including those associated with infections, rheumatoid arthritis and systemic lupus erythematosus, giant-cell arteritis, graft-versus-host disease and disorders associated with lymphocyte-mediated suppression of erythropoiesis.
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PMID:Inhibition by interleukin-1 of the action of erythropoietin on erythroid precursors and its possible role in the pathogenesis of hypoplastic anaemias. 349 70

Two distinct T-cell glycoforms of CD43 result from differential glycosylation of a single gene product in vivo. The 115 kDa glycoform carries mainly tetrasaccharides and is a pan T-cell marker, whereas the 130 kDa glycoform carries mainly hexasaccharides and is associated with T-cell activation. CD43 has been shown to play a role both in enhancing and inhibiting cell adhesion; however, the function of the individual glycoforms is unknown. We have examined the distribution and regulation of the CD43 glycoforms in a murine model of acute graft-versus-host disease (GVHD) using monoclonal antibodies (mAbs) S7 and 1B11 specific for the 115 and 130 kDa CD43 glycoforms, respectively. An increase in T-lymphocyte CD43 130 kDa expression occurred during GVHD from day 4 onwards and coincided with splenomegaly and upregulation of the beta 1-6GlcNAc transferase (C2GnT), the key enzyme responsible for the addition of complex O-glycan branching to CD43. When T-lymphocyte subsets were examined for CD43 expression, we found that in GVHD, both CD43 glycoforms were upregulated on CD4+ T cells. However, in CD8+ T cells, CD43 115 kDa was downregulated while CD43 130 kDa was dramatically upregulated, such that two distinct CD8+1B11+ T-cell subsets were observed. These data demonstrate differential expression of the CD43 glycoforms in both resting and activated CD4+ and CD8+ T cells, and suggest that glycosylation differences between the CD43 glycoforms may reflect participation in the different functions of these T-cell subsets in immune disorders in vivo.
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PMID:Differential regulation of CD43 glycoforms on CD4+ and CD8+ T lymphocytes in graft-versus-host disease. 753 57

Interleukin-1 (IL-1) molecules are cytokines involved in the acute-phase response against infection and injury. Three naturally occurring IL-1 molecules are known, two agonists: IL-1 alpha and IL-1 beta, and one antagonist, the IL-1 receptor antagonist (IL-1ra). Although IL-1 action protects the organism by enhancing the response to pathogens, its overproduction can lead to pathology and has been implicated in disease states that include septic shock, rheumatoid arthritis, graft versus host disease and certain leukemias. The crystal structure of IL-1ra has been solved at 0.21-nm resolution by molecular replacement using the IL-1 beta structure as a search model. The crystals contain two independent IL-1ra molecules which are very similar. IL-1ra has the same fold as IL-1 alpha and IL-1 beta. The fold consists of twelve beta-strands which form a six-stranded beta-barrel, closed on one side by three beta-hairpin loops. Cys69 and Cys116 are linked via a disulfide bond and Pro53 has been built in the cis-conformation. Comparison of the IL-1ra structure with the IL-1 alpha and IL-1 beta structures present in the Protein Data Bank shows that a putative receptor interaction region, involving the N-terminus up to the beginning of strand beta 1 and the loops D and G, is very different in the three IL-1 molecules. Other putative interaction regions, as identified with mutagenesis studies, are structurally conserved and rigid, allowing precise and specific interactions with the IL-1 receptor.
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PMID:Refined crystal structure of the interleukin-1 receptor antagonist. Presence of a disulfide link and a cis-proline. 786 45

Mik beta 1 is a mouse mAb directed at the beta-subunit of the human IL-2R (Tac) that inhibits IL-2 binding and inhibits IL-2 induction of large granular lymphocytes (LGL). Mik beta 1 alone does not inhibit IL-2-induced T-cell proliferation, but acts synergistically with anti-Tac to inhibit IL-2-induced proliferation of activated T cells. To evaluate these effects for possible therapy in humans, we constructed two humanized Mik beta 1 antibodies by combining the complementarity-determining regions of the murine antibody with human framework and constant regions. Compared with murine Mik beta 1, the two humanized Mik beta 1 antibodies, which differ in their degree of humanization, had similar affinities for IL-2R beta. The murine Mik beta 1 and one of the humanized Mik beta 1 antibodies were equivalent in competing for IL-2 binding to IL-2R beta and inhibiting IL-2 induction of LGL cytotoxicity. The activity of the second humanized antibody was significantly reduced. The three Mik beta 1 antibodies act synergistically to varying degrees with humanized anti-Tac to prevent IL-2-induced proliferation of activated T cells. This capacity to synergize paralleled their abilities to inhibit IL-2 binding. In addition, both humanized antibodies directed antibody-dependent cell-mediated cytotoxicity. We hope that humanized Mik beta 1 in combination with humanized anti-Tac will provide a new immunosuppressive therapy for the treatment of autoimmune diseases, graft-versus-host disease, and prevention of allograft rejection.
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PMID:Humanized Mik beta 1, a humanized antibody to the IL-2 receptor beta-chain that acts synergistically with humanized anti-TAC. 833 91

A 19-year-old woman with acute lymphoblastic leukemia received an allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling during the second remission, on September 28, 1993. The conditioning regimen consisted of total body irradiation and cyclophosphamide. Short term methotrexate and cyclosporin A were given for prophylaxis of graft-versus-host disease (GVHD). On day 771 after BMT, she complained of bilateral forearm pain, and developed sclerotic lesions on the skin of the abdominal wall, forearms and legs. The diagnosis of sclerodermatous GVHD was established by skin biopsy on day 834. The values of CRP and IgG were elevated, and both antinuclear antibody and anti-DNA antibody became positive. Flow cytometric analysis showed a significant increase in the number of CD57+ cells after appearance of sclerotic change. In addition, 65% of CD8+ cells were positive for CD57. Circulating level of transforming growth factor (TGF)-beta 1 was high. These results suggest that overproduction of CD8+ CD57+ T cells and high level of circulating TGF-beta are related to the development of sclerodermatous GVHD.
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PMID:[An analysis of sclerodermatous graft-versus-host-disease after allogeneic bone marrow transplantation: CD8+CD57+T-cell proliferation and increased production of TGF-beta]. 957 41

Expansion of donor-derived lymphocytes after allogeneic stem cell transplantation is a serious and sometimes fatal complication. Lymphoproliferative disorders are reportedly caused mainly by reactivation of Epstein-Barr virus (EBV) and non-EBV-associated secondary lymphoma or leukemia. In this paper, we report massive proliferation of CD4+ lymphocytes in peripheral blood of a patient with chronic graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation (alloBMT) from an HLA-identical sibling donor. The abnormal lymphocytes showed CD3low, CD4+, CD8-, CD2+, CD5+, CD7+, CD25-, CD19-, CD20-, CD21-, CD16-, CD56low, T-cell receptor (TCR)-alpha/beta- and TCR-gamma/delta- phenotypes, and no rearrangement of either TCR-C beta 1 or IG(H)JH was detected from the lymphocytes by Southern blot analysis. EBV was not found in the nuclei of lymphocytes by an immunofluorescence antibody. The lymphoproliferation was resistant against immunosuppressive drugs, administered for the treatment of chronic GVHD, and it effectively inhibited aggravation of the chronic GVHD. Although antithymocyte globulin and cytosine arabinoside were administered later, the patient died of respiratory failure with bilateral pleural effusion and interstitial pneumonia. Because we found no evidence of monoclonality of the abnormal lymphocytes, we could not conclude that this patient had suffered from malignant lymphoproliferation. To our knowledge, this is the first case report of proliferation of CD4+ lymphocytes in a patient with chronic GVHD following alloBMT. In this paper, we discuss the possible pathophysiology of the patient.
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PMID:Proliferation of CD4+ lymphocytes in a patient with chronic graft-versus-host disease after allogeneic bone marrow transplantation. 1090 61

The aim was to evaluate two transplant strategies for patients who lack HLA-identical donors, namely HLA-A, HLA-B or -DR beta 1 mismatched unrelated donor (MM URD) transplants (n=14) and umbilical cord blood transplants (UCB, n=27). Diagnosis, disease stage and age were similar in the two groups. Cell dose was lower in the UCB group (P<0.001). Median time to ANC of >0.5 x 10(9)/l was 30 days in the UCB group and 17 days in the MM URD group (P=0.002). Engraftment of plt was delayed in the UCB group (P=0.03). The UCB patients required fewer erythrocyte transfusions (P=0.001). At 100 days, complete donor chimerism for CD3 was 63 and 44% in the UCB and MM URD groups, respectively. Acute GVHD of grades II-IV were 30% in the UCB group and 21% in the MM URD group. The corresponding figures for chronic GVHD were 9 and 20%, respectively. TRM was 30% in the UCB patients and 50% in the MM URD patients. Three-year survival was 66% in the UCB group and 14% in the MM URD group (P=0.006). Although the material is small and heterogeneous, engraftment was delayed, leukocyte chimerism was not significantly different and survival was superior using UCB rather than MM URD transplants.
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PMID:Unrelated cord blood and mismatched unrelated volunteer donor transplants, two alternatives in patients who lack an HLA-identical donor. 1876 60