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)

HLA-DR expression on epidermal keratinocytes was studied in leukemic recipients of allogeneic marrow in order to clarify its relationship to GVHD, investigate its diagnostic value, and gain insight into the pathogenetic mechanisms. Using frozen-section immunohistological techniques, positive keratinocytes were encountered in a small minority of normal donors and in a few recipients prior to transplantation. In patients receiving marrow unpurged of T lymphocytes, keratinocyte HLA-DR staining was found in the majority of patients with, and in about one third of those without, histological evidence of GVHD. Positivity was strongly related to the presence of a rash and was more likely to be found if the interval between the onset of the rash and biopsy exceeded 24 hr. There was a strong association between the presence of positive cells and the subsequent development of systemic GVHD, indicating that staining for HLA-DR on keratinocytes may be a useful adjunct to conventional morphological analysis in the interpretation of post-transplant skin biopsies. Positivity was not observed in patients who received marrow depleted of T lymphocytes, indicating a crucial role for these cells in stimulating keratinocyte HLA-DR expression. Sequential studies, however, showed that keratinocyte positivity preceded lymphocytic infiltration of the epidermis.
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PMID:HLA-DR expression in epidermal keratinocytes after allogeneic bone marrow transplantation. Relationship to histology, rash, marrow purging, and systemic graft-versus-host disease. 306 Oct 79

Immunohistochemical analysis of oral lichen-planus-like eruption (LPLE) in graft-versus-host disease (GVHD) using monoclonal antibodies (MoAbs) was performed on five patients after allogeneic bone marrow transplantation (BMT) for leukemia. In the mucosal lesions of LPLE in GVHD, the major population of infiltrated lymphocytes in the areas of upper lamina propria (Lp), basal cell layer (Bc), and epithelium above the basal cell layer (Ep) were T-cells (Leu-1+, Leu-4+) and expressed the phenotype associated with suppressor/cytotoxic T-cells (Leu-2a+) rather than helper/inducer T-cells (Leu-3a+). Some of the infiltrated lymphocytes in the areas of Lp, Bc, and satellite cell necrosis (SCN) bore interleukin-2 (IL-2) receptor. HLA-DR antigen was expressed on keratinocytes in the LPLE lesions. Immunoelectron micrographs showed various degrees of degeneration of keratinocytes to which Leu-2a+ cells attached, whereas those with accidentally attached Leu-3a+ cells preserved normal structures. These findings suggest that cellular immunity mediated by cytotoxic T-cells may play a major role in the pathogenesis of oral LPLE in GVHD.
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PMID:Immunohistochemical analysis of oral lichen-planus-like eruption in graft-versus-host disease after allogeneic bone marrow transplantation. 327 80

Using immunohistological techniques the number of leucocytes present in the epithelium and lamina propria of the rectal mucosa were assessed in 16 allogeneic bone marrow transplant recipients, with and without evidence of graft-versus-host disease (GVHD), and compared with a non-transplant group of patients. Samples were obtained between 15 and 198 days after transplant. In marrow recipients without GVHD, compared with non-transplant cases, there was a decrease in T lymphocytes in the lamina propria due to a reduction in the helper-inducer (T4+) subset with no change in suppressor-cytotoxic (T8+) cells or epithelial leucocytes. In GVHD, the number of T lymphocytes increased both in the lamina propria and epithelium due to an increase in T8+ cells with no change in T4+ cells. Lymphocytes did not express the activation markers detected by Tac, OKT10 or HLA-DR. Macrophages and natural killer cells were not changed after transplant or in GVHD. Epithelial HLA-DR expression was detected in seven out of eight in the GVHD group, three out of eight in the non-GVHD transplant group and two out of eight in the non-transplant cases. These findings show several differences from those we have observed in cutaneous and hepatic GVHD. Although elevated numbers of T8+ cells are common to GVHD in all three sites, the precise role of these cells in producing epithelial damage is not clear.
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PMID:Changes in rectal leucocytes after allogeneic bone marrow transplantation. 330 37

Induced class II histocompatibility antigens have been observed in the target tissues of rodents and humans with acute graft-versus-host disease (GVHD). Possibly this expression triggers the target tissue phase, through antigen presentation, lymphocyte recruitment, or additional antigenic stimulus. We have tested whether the induced expression is required for cutaneous GVHD in human marrow recipients. Ninety-two skin biopsies from 37 allogeneic marrow recipients at the Johns Hopkins Bone Marrow Transplant Unit were stained for HLA-DR, OKT6 (Langerhans cells), and for surface markers of lymphocyte and monocytes. Of 22 biopsies taken at the onset of GVHD, 12 did not have detectable HLA-DR antigen, and 10 had patchy-to-diffuse expression. The biopsies with HLA-DR- GVHD consisted primarily of epithelial infiltrates of cytotoxic/suppressor cells (CD8+), while those with HLA-DR+ GVHD had a mixed infiltrate with more helper/inducer/class-II-reactive cells (CD4+) in the epidermis and dermis and more monocytes in the dermis. Eight of 9 patients with HLA-DR- GVHD had follow-up biopsies that later expressed epithelial DR antigen, but the epidermal and dermal infiltrates showed no significant changes. Most of those receiving cyclosporine (CsA) prophylaxis (7/9) developed HLA-DR- GVHD, while those receiving cyclophosphamide were split between the two groups (8 of 13 were HLA-DR+). HLA-DR antigen expression was evident in some biopsies with no GVHD or minimal GVHD but did not appear to predict the development of GVHD or the type of GVHD. HLA-DR antigen expression was not evident in 2 of 3 initial biopsies of lichenoid-type chronic GVHD. Class II antigen induction is clearly not necessary for the target phase in most patients of this study.
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PMID:Epithelial class II antigen expression in cutaneous graft-versus-host disease. 330 48

A major hypothesis to explain the immunodeficiency associated with bone marrow transplantation states that thymic epithelial damage due to graft-versus-host disease (GVHD) abrogates or delays the recovery of normal immunologic function. This study evaluated the thymus glands of 36 human bone marrow transplant recipients dying between 4 and 1742 days after transplant using histology, histochemistry, and immunohistology. The observations lead to a model of thymic damage by irradiation, chemotherapy, and GVHD in which early injury by all three of these agents results in profound thymic atrophy followed by long-delayed restitution. Patients undergoing total body irradiation showed more severe damage to thymic cortical and medullary epithelium than did patients undergoing chemotherapy alone as preparation for transplantation. Patients with GVHD showed additional damage in the form of individual thymic epithelial cell death and showed HLA-DR surface protein expression on thymic epithelium during GVHD. Longer-term survivors showed a profoundly delayed restitution of normal thymic epithelium and delayed evidence of restored lymphopoiesis. A few patients dying late after transplant showed evidence of reconstitution of normal thymic structure or nodules of lymphopoiesis in focal areas of epithelial-cell reconstitution. Evidence of such lymphopoiesis was seen at times ranging between 90 and 1742 days after grafting. The data are consistent with a model of long-standing thymic damage caused by GVHD which is reversible after the development of tolerance.
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PMID:Pathology of the thymus after allogeneic bone marrow transplantation in man. A histologic immunohistochemical study of 36 patients. 331 29

A comparative study of the healthy skin of patients who had undergone bone marrow grafting and not developed graft-versus-host disease (GVHD) and of patients with cutaneous lesions of acute GVHD has been carried out. The aim of this study was to assess the diagnostic value of cutaneous immunopathology in the diagnosis of acute GVHD. A double-labelling immunofluorescence technique was used with a panel of monoclonal antibodies. The results showed a lack of specificity for GVHD in the distribution of Langerhans cells, but confirmed the diagnostic value of HLA-DR staining of epidermal keratinocytes. Cellular polymorphism of the T cell infiltrate in the dermis was observed (T helpers 40% and T suppressors 20%). The expression of the 55-57 Kd keratin polypeptide and of bullous pemphigoid antigen showed modification during acute GVHD while that of pemphigus antigen remained unchanged.
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PMID:Cutaneous immunological studies in diagnosis of acute graft-versus-host disease. 351 Jun 54

Using immunohistological techniques, leucocytes were enumerated in portal tracts and bile duct epithelium in bone marrow transplant recipients with and without evidence of hepatic graft versus host disease (GvHD) and compared with normal subjects. Samples were obtained 8-169 days after transplantation. In marrow recipients without graft versus host disease (GvHD), inducer and suppressor/cytotoxic lymphocytes were reduced in number in the portal tracts compared with normal subjects. In GvHD, suppressor/cytotoxic lymphocytes were increased relative to non-GvHD recipients, but did not exceed normal values, while inducer cell numbers remained low. Natural killer cells (HNK1+) were not found in normal subjects, were present in small numbers in non-GvHD transplant cases and significantly increased in GvHD. The total number of portal tract leucocytes was not elevated in GvHD and the changes in the relative proportions of cells were similar to those that have been observed in the peripheral blood after transplantation. There was no increase in the number of lymphocytes expressing the activation markers Tac, T10 and HLA-DR nor in the number of leucocytes within the bile duct epithelium itself. These findings differ from those we have previously obtained in a similarly treated group of patients with cutaneous GvHD where lymphocytes were increased in the epithelium and stroma and expressed activation markers. Like the epidermis of the skin, however, the bile duct epithelium showed increased staining for HLA-DR antigens in all cases, but focal staining was also present in four of the seven marrow recipients without GvHD. The significance of these findings is discussed.
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PMID:An immunohistological study of human hepatic graft-versus-host disease. 391 Mar 17

The major limitation of mismatched bone marrow transplantation is fatal graft versus host disease (GVHD). We processed haplotype-identical parental marrow with soybean agglutinin (SBA), sheep erythrocytes (SRBC), and neuraminidase-treated SRBC (N-SRBC) to enrich for marrow stem cells and remove mature T cells. Nine patients with severe combined immunodeficiency disease (SCID) who lacked histocompatible donors received these SBA-negative, SRBC-negative, N-SRBC-negative marrow transplants (0.5-5.0 X 10(8) cells/kg). Seven of the nine patients (78%) had documented T-lymphocyte engraftment based on HLA typing and/or chromosomal analysis. Six patients showed evidence of B-cell immunity on the basis of increased immunoglobulin levels, isohemagglutinins, and/or HLA-DR typing of non-T cells. Three patients received marrow ablative chemotherapy pretransplant for maternal-fetal GVHD; neutrophil engraftment occurred between 9 and 17 days posttransplantation, erythrocytes engrafted within 3-4 weeks of transplantation, and platelet recovery was seen between day 17 and day 49 following the transplants. No immunosuppression was given prophylactically posttransplant. Three patients had no GVHD, two had transient rash and/or fever, and two developed mild focal (stage I) chronic cutaneous GVHD. Of the seven who engrafted, five (71%) are alive and clinically well without GVHD 18-35 months posttransplant. These data demonstrate that SBA- and SRBC/N-SRBC-treated haploidentical marrow transplantation results in functional lymphocyte engraftment in SCID without significant GVHD, and can be used for some patients who otherwise would have no hope for survival.
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PMID:Haploidentical bone marrow transplantation for severe combined immunodeficiency disease using soybean agglutinin-negative, T-depleted marrow cells. 391 Jun 75

We have observed marked depletion of epidermal dendritic cells, defined by monoclonal antibodies directed against HLA-DR (Ia-like) and T6 antigens, after allogeneic bone marrow transplantation. To more precisely characterize this observation, we examined a total of 39 sequential biopsies from 15 patients both before and after allogeneic bone marrow transplantation. Profound depletion of HLA-DR and T6-positive epidermal dendritic cells was observed early after transplantation (1-4 weeks), followed by gradual and variable repopulation. Transmission electron microscopy confirmed absence of dendritic cells in selected biopsies. Depletion of dendritic cells did not appear to be related to development of clinical or histologic evidence of graft-versus-host disease, suggesting that depletion may relate to pretransplant conditioning regimens. The rate of return of these cells, however, may be influenced by the presence or persistence of clinical disease. Repopulation of epidermal dendritic cells after initial depletion in bone marrow transplantation represents a human model relevant to studies concerned with the origin and kinetics of Langerhans cells.
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PMID:Depletion and repopulation of epidermal dendritic cells after allogeneic bone marrow transplantation in humans. 391 9

Recombinant human gamma interferon (r-IFN-gamma) induces the synthesis and expression of HLA-DR antigen on cultured, normal, human keratinocytes depleted of Langerhans cells. After removal of r-IFN-gamma from the culture medium of keratinocytes that are expressing HLA-DR antigen, the cells continue to express this antigen for at least 2 days. r-IFN-gamma induces, in a dose dependent fashion, the synthesis of several triton-soluble proteins with the most prominent having an apparent molecular weight of 53,000. Whereas normal keratinocytes do not express HLA-DR antigen in vivo, they do express HLA-DR in a variety of skin diseases such as lichen planus, graft-versus-host disease, and mycosis fungoides. We propose that an understanding of lymphocyte-keratinocyte interactions in vivo may be achieved by further studies of the mechanism of action of r-IFN-gamma on cultured keratinocytes and that the results may provide insight into the patho-physiology leading to a number of common inflammatory and neoplastic skin diseases.
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PMID:Induction of the synthesis of triton-soluble proteins in human keratinocytes by gamma interferon. 392 29


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