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 a study carried out for patients receiving intrafamilial HLA-A,B,DR identical, MLC negative bone marrow transplants, RFLP profiles of HLA-class II for 27 donor recipient pairs were analyzed. Twenty-four pairs were found HLA-class II identical while three pairs were HLA-DP incompatible. The patients of these three pairs did not reveal any acute GVHD greater than or equal to grade II. The seven cases of acute GVHD greater than or equal to grade II found in our panel were HLA-DR, DQ, and DP compatible. Thus, in practical terms pretransplantation HLA-DP typing does not seem necessary for intrafamilial HLA-identical, MLC negative BMT. On the other hand, this work confirmed that it is possible to type for HLA-DP using molecular biological techniques, and this in itself may have some important implications for unrelated BMT.
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PMID:HLA-DP genotyping in HLA-A,B, and DR identical intrafamilial bone marrow transplantation. 196 10

Sixteen recipient-donor pairs who underwent unrelated BMT were analyzed for their HLA-class II identity by DNA-RFLP, in order to evaluate the importance of the genotypic HLA-DR, DQ, DP identity in the clinical outcome of unrelated bone marrow transplantation. From our study, a clear correlation between the HLA-DR, DQ, and DP genetic identity and acute GVHD (aGVHD) is not obvious since the number of studied cases is still limited. Nevertheless, it seems that the genetic identity influence the clinical outcome and patient survival. Six patients out of the ten who experienced severe aGVHD (greater than grade II) differed from their respective donors by HLA-DP mismatch in the GVH direction. Two patients rejected their grafts, and both presented HLA-DP incompatibilities in both GVH and HVG directions. Hence, HLA-DP may function as a transplantation antigen like the other HLA-class II molecules (DR, DQ) in unrelated BMT. Accordingly, we propose considering it in the pretransplantation histocompatibility testing. Nevertheless, further studies with larger numbers of cases should be done in order to confirm the role of HLA-DP. No correlation was observed between the mixed lymphocyte reaction (MLR) reactivity and the incidence of aGVHD. Accordingly, MLR response seems to be an incomplete indicator of GVHD, and a functional test is still to be found.
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PMID:HLA-DR, DQ, and/or DP genotypic mismatches between recipient-donor pairs in unrelated bone marrow transplantation and transplant clinical outcome. 197 52

We have analyzed the immunocompetence of blood donor-derived, allogeneic T cells that had engrafted in a patient with severe combined immunodeficiency following transfusion with unirradiated blood. The blood donor T cells multiply and persist in the patients' bone marrow and peripheral blood over several months without leading to a graft-versus-host disease. The allogeneic T cells can be expanded in vitro and restimulated by cells expressing host HLA-DR antigens. The presence of blood donor-derived T cells prevented engraftment of a bone marrow graft from an HLA-identical sibling; in contrast, engraftment and immunological reconstitution by bone marrow donor-derived cells was seen following elimination of the allogeneic T cells in vivo. We conclude that the allogeneic T cells sensitized against host histocompatibility antigens were responsible for bone marrow graft failure, even though this sensitization did not lead to a graft-versus-host disease.
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PMID:Stable engraftment of allogeneic T lymphocytes in a patient with severe combined immunodeficiency following a transfusion with unirradiated blood. Specific recognition of host histocompatibility antigens and engraftment failure of a bone marrow transplant HLA-identical to the host. 201 36

Graft-versus-host reactions are mediated by subpopulations of donor T cells and can be attributed to host specific minor histocompatibility (mH) antigens. We isolated strong anti-host mH antigen proliferative T cell lines, LG2, PN2, and LH3, from three patients suffering from acute graft-versus-host disease (GVHD). To study the role of the different major histocompatibility complex (MHC) molecules in the anti-host mH antigen specific proliferative response, the reactivities of the three T cell lines were analysed in primed lymphocyte test (PLT) assays against panels of stimulator cells obtained from unrelated blood donors. LG2 and LH3 stimulating determinants were commonly detected in the unrelated panel, whereas the PN2 T cell line recognized a rare specificity. The responses were associated with the presence of self HLA-DR molecules on the stimulator cells, although not all DR sharing stimulator cells were recognized. The proliferative responses of LG2, LH3 and PN2 cells could be blocked by monoclonal antibodies (MoAbs) against HLA-DR, but not by MoAbs against HLA-A/B/Cw, HLA-DQ or -DP. At the responder cell level, depletion of CD4 cells as well as blocking with CD4 specific MoAbs abrogated the specific responses of the three T cell lines. Our findings suggest that anti-host Th cell responses activated in the acute phase of GVHD are directed against both frequent and rare mH antigens, are mediated by CD4 + ve class II restricted Th cells, and use the HLA-DR molecule as a common restriction element for mH antigen presentation.
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PMID:Graft-versus-host disease associated T helper cell responses specific for minor histocompatibility antigens are mainly restricted by HLA-DR molecules. 214 41

Major histocompatibility complex antigens are critical to an animal's immune response. In most animals, the extreme polymorphism of MHC molecules complicates studies of the role of this complex in the immune response. In mice, however, MHC haplotype-homozygous inbred strains have been developed which are invaluable in the study of the immune system and the search for immune response genes. The human MHC bears many similarities to its murine equivalent with regard to antigen structure and polymorphism; furthermore, a number of combinations of specific MHC alleles between HLA-B and HLA-DR/DQ (extended haplotypes) are found in people more commonly than predicted by individual allele frequencies. Over 30 percent of Caucasian haplotypes are extended haplotypes, and over 55 percent of individuals have at least one extended haplotype. Examples of the same extended haplotype, even in unrelated individuals, should either all have or lack any gene within the MHC region. The value of considering extended haplotypes in searching for associations between the MHC and diseases, or immune response, is shown in three examples: congenital adrenal hyperplasia, hepatitis B immunization, and transfusion-associated graft-versus-host disease.
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PMID:The major histocompatibility complex: the value of extended haplotypes in the analysis of associated immune diseases and disorders. 229 6

A 32-year-old male patient with chronic myelocytic leukemia in accelerated phase received a bone marrow allograft from his 42-year-old HLA/MLC-identical sister. He recovered from acute graft-versus-host disease (GVHD) grade III-IV of skin, liver and gut, but chronic GVHD of progressive onset developed. On day 556 post-graft severe thrombocytopenia was resistant to prednisolone, cyclophosphamide and high dose immunoglobulin. Splenectomy was followed by a normalization of platelet counts. The subsequent clinical course was characterized by progressive muscular atrophy and weight loss. Dysphagia, dysarthria, cachexia and ultimately recurrent pneumonic episodes ensued. The cachectic patient developed a highly abnormal breathing pattern with hypoventilation and intermittent apnea requiring mechanical ventilation. Auditory evoked potentials revealed a considerable dysfunction of the brainstem. The patient died on day 1120 post-graft from pneumonia, aggravated by thoracic muscular insufficiency. Postmortem examination revealed diffuse predominantly lymphoid perivascular infiltration in meninges and CNS tissue; proliferation of activated microglial cells expressing the HLA-DR antigen was prominent in the brainstem. These histologic changes are similar to those observed in the CNS in experimental GVHD. We suggest that this case represents the first documentation of CNS involvement in chronic GVHD.
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PMID:Fatal encephalitis in a patient with chronic graft-versus-host disease. 239 Jun 33

Dermatopathologists observe mononuclear leukocytes in close apposition to keratinocytes (KCs) in graft versus host disease and in other lymphocyte-mediated skin diseases, such as lichen planus, erythema multiforme, and lupus erythematosus. Since the KCs are Class II histocompatibility antigen (HLA-DR) positive in these diseases (indicating local production of gamma interferon, IFN-gamma, by activated T-cells), we sought to determine whether IFN-gamma treatment of KCs would influence the ability of allogeneic peripheral blood mononuclear leukocytes (PBMLs) to adhere to cultured KCs in vitro. The adherence of PBMLs to KC monolayers was determined by the three following methods: (a) methanol fixation of the washed KCs (after PBML incubation), followed by hematoxylin-eosin staining and direct counting of adherent PBMLs; (b) fluorescein isothiocyanate (FITC) labeling of PBML, followed by measuring the amount of FITC-PBML bound to KCs after washing either by direct visualization with a fluorescence microscope; or by (c) quantitative fluorescence spectroscopy following lysis of the adherent cells. While untreated KCs bound allogeneic PBMLs minimally 15-120 min at 37 degrees C, pretreatment of the KCs with IFN-gamma (300 U/ml, 3 days) produced significantly increased binding of the PBMLs by approximately fivefold. By contrast, IFN-alpha and IFN-beta (10(3) U/ml) had no effect. Also, despite the induction of HLA-DR on cultured human fibroblasts, no increased binding of PBMLs after IFN-gamma treatment was observed. The selective ability of IFN-gamma to produce a marked increase in adherence between KCs and PBMLs suggests a new role for IFN-gamma in the immunobiology of the skin.
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PMID:Enhanced binding of peripheral blood mononuclear leukocytes to gamma-interferon-treated cultured keratinocytes. 244 18

Because keratinocytes (KCs) express HLA-DR in a wide variety of skin diseases in which mononuclear leukocytes are observed in close apposition to KCs (i.e., graft-versus-host disease), and since gamma interferon (IFN-gamma) induces HLA-DR expression on KCs, we asked whether IFN-gamma treatment of KCs would influence the adherence of mononuclear leukocytes. When allogeneic peripheral blood mononuclear leukocytes (PBML) and a Leu-3+ T cell clone were coincubated with IFN-gamma-treated KCs (300 U/ml, 3 days), there was a marked increase in binding compared with nontreated KCs. Similar binding results were obtained using a cutaneous squamous carcinoma cell line (SCL-1) after IFN-gamma treatment. The IFN effect was relatively specific for IFN-gamma, as neither IFN-alpha nor -beta had any effect. Tumor necrosis factor exposure (500 U/ml, 3 days) increased the binding of the Leu-3+ T cell clone to both KCs and SCL-1 cells. Neutrophils displayed a less marked (but statistically significant) increase in binding to IFN-gamma-treated KCs. Using the Leu-3+ cell clone and SCL-1 cells, detailed kinetic analysis of the effect of IFN-gamma on binding was performed. The increased adherence between the cells began to appear after only 7 hours of treatment with r-IFN-gamma (300 U/ml) and reached a plateau at 48 hours, with significantly enhanced binding continuing for at least 48 hours after removal of IFN-gamma. The mechanism of binding was explored by preincubation of the PBML/Leu-3+ T cells with anti-LFA-1 (lymphocyte function-associated antigen) antibody (0.6-6.0 micrograms/ml), which totally inhibited the binding with no effect by anti-LFA-2 or -3 or class I or II antibodies despite documented binding of these antibodies to the cells. These results suggest that, after exposure to IFN-gamma, the ability of KCs to bind mononuclear leukocytes is strongly enhanced, and this adherence may be important in leukocyte trafficking in the skin as well as contributing to altered KC-leukocyte interaction, which may be of fundamental importance in a variety of skin disease.
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PMID:Recombinant gamma interferon increases the binding of peripheral blood mononuclear leukocytes and a Leu-3+ T lymphocyte clone to cultured keratinocytes and to a malignant cutaneous squamous carcinoma cell line that is blocked by antibody against the LFA-1 molecule. 244 90

HLA-DR expression by keratinocytes and enterocytes was studied in 23 patients undergoing BMT (12 autologous; 11 allogeneic). Two monoclonal antibodies were used to detect the HLA-DR antigen. Only in two patients before transplant and in one following autologous BMT was HLA-DR expressed on keratinocytes. Of 11 allogeneic recipients, 7 developed clinical GVHD, and HLA-DR-positive keratinocytes were seen in 6 of these. HLA-DR was expressed by enterocytes in 5 patients with GVHD and 4 of these also showed HLA-DR expression by keratinocytes. HLA-DR expression by keratinocytes correlated well with clinical GVHD. Expression of this antigen by enterocytes was associated with characteristic histological appearances of GVHD, even in the absence of intestinal symptoms. A combination of traditional and immunocytochemical techniques offers a sensitive and accurate method of confirming GVHD before it becomes florid.
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PMID:Class II antigen expression by keratinocytes and enterocytes--an early feature of graft-versus-host-disease. 245 41

Many skin diseases, such as graft-versus-host disease (GVHD), are marked by lymphocyte infiltrates in the skin. Severity of these diseases is often correlated with the induced expression of class II antigens (human, HLA-DR,; murine, Ia) by the keratinocytes. This suggests that HLA-DR-expressing keratinocytes may be involved in the pathogenesis of these diseases. Since some of these diseases are effectively treated with ultraviolet radiation (UVR), this study was conducted to determine whether UVR alters the keratinocyte expression of class II antigens. To test this hypothesis, 2 models of experimentally induced keratinocyte Ia expression were employed. First, athymic nude mice with one ear protected by electrical tape were exposed to UVR (450 J/m2/day on 4 consecutive days). They were then given an i.v. injection of normal mouse serum (NMS) to induce keratinocyte Ia expression. Keratinocytes in the UVR-exposed skin of these animals were not induced to express Ia; however, Ia-expressing keratinocytes were observed in the epidermis of shielded skin sites. Likewise, it was determined that UVR was capable of downregulating keratinocyte expression of Ia when administered to nude mice 7 d after receiving an injection of NMS. Second, employing a clinically relevant model, we found that Ia expression by keratinocytes in mice undergoing experimentally induced GVHD was abrogated by UVR treatment. This appeared to be a direct effect of the UVR, since keratinocytes in shielded skin sites and mucosal cells in the intestinal epithelium of animals with GVHD were shown to express Ia. These data provide compelling evidence for our hypothesis that decreased HLA-DR expression by keratinocytes in diseased skin treated with UVR is a mechanism by which UVR exerts its therapeutic effect.
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PMID:Effect of ultraviolet radiation on Ia expression by keratinocytes. 256 38


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