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)

Human cord blood is an attractive alternative to marrow-derived stem cells for transplantation. Experiences with cord blood transplants suggest that graft-versus-host disease (GvHD) may be less readily induced, even in the face of HLA differences. However, this decreased potential for GvHD might also abrogate the graft-versus-leukemia (GvL) effects of the transplant. The GvL potential might be doubly compromised since cord blood NK activity is also decreased. We have compared alloreactivity, NK cell activity and lymphokine-activated killer cell (LAK) activity of cord blood mononuclear cells with adult mononuclear cells. We find a reduced (but not absent) alloproliferative, allostimulatory and allocytotoxic capacity of cord blood mononuclear cells. Phenotyping revealed no significant differences in the proportion of T cells in cord-versus-adult blood, but cord blood T cells were nearly all of the naive CD45RA subset. Expression of LFA-1 alpha and LFA-1 beta was normal on resting cord T cells; however, they expressed significantly less ICAM-1 (CD54) than did adult PBMC. Cord blood B cells and monocytes expressed normal levels of HLA Class II. Although no differences were found in NK cell percentages or subsets in resting cord blood, cord blood NK activity was very low. However, LAK activity was much more readily induced in cord blood as compared to adult PBMC, which could be explained in part by a higher frequency of LAK precursors (LAKp). Cord blood LAK cells were readily able to lyse fresh leukemia targets from patients with ALL, AML, and CML.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Characterization of cord blood lymphocyte subpopulations. 792 75

A 45-year-old male with chronic myelocytic leukemia who received a bone marrow transplantation from a phenotypically HLA-matched unrelated donor developed chronic GVHD on day 100 post transplantation. He developed a slight fever, malaise, hepatic dysfunction and extensive itchy erythema with scaling over his entire body. The inflammatory skin lesion developed into erythroderma in about two weeks. H&E staining of a skin biopsy revealed eosinophilic bodies and a lymphocytic infiltration in the dermis and epidermis, which were compatible with the early phases of chronic GVHD. Immunohistochemistry revealed that keratinocytes expressed dense HLA-DR and ICAM-1 epitopes. Langerhans cells (CD1a+ cells) had disappeared from the epidermis. Many T cells (CD3+ cells) had migrated into the epidermis as well as into the reticular dermis. The majority of the T cells in the epidermis were CD8+ cells, while almost all the T cells in the dermis were CD4+ cells. These immunohistochemical features were similar to those previously reported for acute cutaneous GVHD. Despite the corticosteroid therapy, the eruptions did not disappear. The patient was then treated with whole body bath-methoxsalen (Oxsoralen) plus ultraviolet A (UVA). The bath-psoralen plus UVA therapy was effective in this patient.
 ...
PMID:A case of chronic GVHD following bone marrow transplantation from a phenotypically HLA-matched unrelated donor. 805 98

The inflammation-associated molecules intercellular adhesion molecule (ICAM)-1, endothelial lymphocyte adhesion molecule (ELAM)-1, vascular cell adhesion molecule (VCAM)-1, human leukocyte antigen (HLA)-DR, interleukin (IL)-2R (CD25), CD34, alpha-1-antichymotrypsin (alpha 1-ACT), and L1 antigen were studied in skin from marrow recipients to determine the timing and distribution of their expression in relation to the clinical and histologic evolution of graft-versus-host disease (GvHD). Four phases were recognized: 1. pretransplant with no immunohistologic change; 2. posttransplant with no evidence of GvHD when dermal alpha 1-ACT + macrophages were increased; 3. posttransplant with clinical, but not histologic, evidence of GvHD with increased keratinocyte HLA-DR and ICAM-1 expression and increased numbers of VCAM-1+ dermal cells; and 4. posttransplant with clinical and histologic evidence of GvHD characterized by an infiltrate of CD25+ T cells, L1+, alpha 1-ACT+ and VCAM-1+ macrophages, L1 antigen expression on keratinocytes accompanied by further increases in HLA-DR and ICAM-1, and increased endothelial ELAM-1 staining with a reciprocal decrease in CD34. A sequential accumulation of cellular and molecular changes, therefore, occurs in the evolution of acute GvHD, and immunostaining for HLA-DR, ICAM-1, and VCAM-1 may be helpful in diagnosing early disease.
 ...
PMID:A prospective study of cellular and immunologic changes in skin of allogeneic bone marrow recipients. Relationship to clinical and histologic features of acute graft-versus-host disease. 817 66

In a retrospective analysis lung biopsy specimens obtained postmortem from 30 consecutive allogeneic bone marrow transplant recipients who had died of either either interstitial pneumonitis (IP; 18/30 patients) or various other causes (12/30 patients) were studied for the local presence of human cytomegalovirus (HCMV) by culture, in situ hybridization, polymerase chain reaction (PCR) and immunohistochemistry for HCMV proteins. All patients suffering from IP were found to be HCMV positive in the lung biopsy. PCR revealed the highest sensitivity for HCMV detection in lung biopsies, but in 15/18 PCR-positive samples local HCMV infection could be confirmed by at least one additional technique. All the lung biopsies obtained from the 12 patients without IP were negative for HCMV by all techniques applied, except one with a weak HCMV-DNA signal in the PCR assay. The severity of the clinical, as well as histological and immunohistological alterations in the lung did not correlate with the amount of HCMV-DNA or the number of HCMV-positive cells detected in the biopsy. An increase of HLA-class II antigen and of ICAM-1 expression on the alveolar epithelium, as well as presence of activated CD8+ or CD4+ lymphocytes infiltrating only HCMV-positive lung biopsies revealed T cell-mediated immune reactions to be involved in the pathogenesis of IP. Since all analyzed patients presented with severe acute or extensive chronic graft-versus-host disease (GvHD), but only those with pulmonary HCMV infection developed IP, dissemination of HCMV appears to be the primary requirement for the initiation of IP. GvHD, however, may interfere with normal control of subsequent antiviral immune response and, thus, provoke the immunopathology of IP.
 ...
PMID:Correlation of interstitial pneumonia with human cytomegalovirus-induced lung infection and graft-versus-host disease after bone marrow transplantation. 857 11

A 20-year-old woman with aplastic anemia underwent bone marrow transplantation from an HLA-identical sibling after total lymphoid irradiation (TLI) and cyclophosphamide (CY). The post-transplant course was uneventful. CYA was discontinued on day 221. Three weeks later, the patient developed cutaneous GVHD precisely localized to the field of TLI. No other organs were involved. Immunohistochemical staining of the affected skin was strongly positive for ICAM-1, PECAM-1 and ELAM-1; normal skin was only weakly positive for ICAM-1. CYA was restarted, and the skin lesions disappeared. TLI may contribute to an unusual presentation of cutaneous GVHD associated with specific expression of adhesion molecules.
 ...
PMID:Cutaneous chronic graft-versus-host disease localized to the field of total lymphoid irradiation. 867 42

Cytomegalovirus (CMV) is a major pathogen in transplant recipients and AIDS patients, and the virus may also play a role in allograft rejection. Previous work from this laboratory demonstrated increased cell surface expression of the adhesion molecules ICAM-1 (CD54) and LFA-3 (CD58) following CMV infection in vitro. We investigated whether the induction of adhesion molecules by CMV was a direct viral effect or secondary to cytokine induction. Cytokines known to up-regulate ICAM-1, such as TNFalpha or IL-1beta, were not detected in the supernatants of infected fibroblasts, and neutralizing antibodies against these cytokines did not abrogate the induction of either ICAM-1 or LFA-3 by CMV. Infected cell supernatants had increased levels of IL-6, IL-8 and IFNbeta however, the addition of recombinant forms of these cytokines did not affect adhesion molecule expression. Neither virus-free infected cell supernatants nor UV-inactivated virus up-regulated adhesion molecules, demonstrating that the induction of ICAM-1 and LFA-3 by CMV was a direct effect requiring infectious virus. Effective antiviral treatment with ganciclovir or foscarnet accentuated rather than abrogated the up-regulation of adhesion molecules, suggesting that CMV immediate early/early gene expression, which is not blocked by such treatment, was responsible for the adhesion molecule induction. Thus, despite effective antiviral therapy in the transplant recipient, CMV infected cells may continue to provide a focus of proinflammatory activity, which could contribute to immunopathology and/or accentuate graft rejection or graft-versus-host disease in vivo.
 ...
PMID:Cytomegalovirus induced up-regulation of LFA-3 (CD58) and ICAM-1 (CD54) is a direct viral effect that is not prevented by ganciclovir or foscarnet treatment. 890 Mar 10

Mice with chronic graft-versus-host disease (GVHD), induced by injection of DBA/2 lymphocytes in (C57BL10*DBA/2) F1 hybrids, develop a syndrome resembling systemic lupus erythematosus (SLE) with immune complex glomerulonephritis. In this model we evaluated the role of interactions between CD11a (LFA-1alpha) and CD54 (intercellular adhesion molecule-1 (ICAM-1)) molecules on leucocytes in the development of renal disease in systemic autoimmunity. Two weeks after induction of GVHD, when anti-nuclear autoantibodies were detected in the circulation and immune complexes had formed in the glomeruli, mice were injected twice per week with rat anti-CD11a and anti-CD54 MoAbs, or with their vehicle PBS, or with control rat IgG. MoAb treatment significantly lowered albuminuria and increased survival compared with control mice with GVHD. In the glomeruli of MoAb-treated mice there was markedly less binding of immunoglobulin and C3, while anti-renal tubular epithelium autoantibodies, but not anti-glomerular basement membrane autoantibodies, were significantly lowered in the circulation 4 weeks after disease induction. In addition, MoAb treatment inhibited the glomerular influx of CD11a+ cells and decreased development of histological abnormalities in the kidneys. Both rat IgG- and MoAb-treated mice developed anti-rat immunoglobulin antibodies. Furthermore, a marked splenomegaly with an increase of the T cell compartment was observed in MoAb-treated mice with GVHD. These results show that CD11a/CD54 interactions are crucial for the full-blown development of lupus nephritis in this model. Treatment aimed at blocking the activity of these molecules profoundly attenuated the development of renal disease in chronic GVHD even if started when first symptoms of SLE (i.e. anti-nuclear autoantibodies in sera and glomerular binding of immunoglobulins) were already detectable.
 ...
PMID:Effective treatment of experimental lupus nephritis by combined administration of anti-CD11a and anti-CD54 antibodies. 915 6

Intensity of pretransplant conditioning has been closely correlated with regimen related toxicity in patients receiving allogeneic bone marrow transplantation (BMT). In this review, we summarize evidence for a direct link between inflammatory reactions induced by irradiation and cytotoxic treatment and occurrence of acute graft-versus-host disease (GvHD) as well as endothelial complications: In our studies, de novo release of TNFalpha during conditioning was associated with an increased risk of severe GvHD and mortality following BMT, whereas increased spontaneous production of IL-10, an endogenous TNF-antagonist, prior to conditioning protected from these complications. Immunogenetic differences in cytokine regulation and costimulation by endotoxin proved to be important cofactors determining the extent of inflammatory cytokine release in individual patients. Pathophysiological relevance of these findings seems to be confirmed by experimental as well as first clinical trials using TNF-antibodies and related antagonists during pretransplant conditioning. Preclinical experiments suggest additional, cytokine independent inflammatory reactions induced by irradiation such as expression of ICAM-1 and endothelial cell apoptosis. Although the exact impact of these findings on pathophysiology of BMT related complications needs further clarification by future studies, conditioning related inflammation as a first crucial step in induction of GvHD and complications has to be considered when designing new protocols for preparation of patients for allogeneic BMT.
 ...
PMID:Inflammatory reactions induced by pretransplant conditioning--an alternative target for modulation of acute GvHD and complications following allogeneic bone marrow transplantation? 916 32

The diagnosis of post-transfusion graft-versus-host disease (GVHD) in early period is critical for the prognosis of the patients. Exanthema and fever are the earliest symptom of the post-transfusion GVHD and usually precede the disturbance of the liver and bone marrow. Snap-frozen, cryostat-sectioned specimens from the lesional and perilesional skin were labeled by monoclonal antibodies against HLA-ABC, HLA- DR, ICAM-1, CD1a and CD8. The reaction was visualized by indirect immunofluorescence. Graft-versus-host reaction (GVHR) was immunopathologically characterized by extensive expression of HLA-DR and ICAM-1 in the epidermal keratinocytes, exocytosis of CD8 positive cytotoxic T-cell and the reduction or disappearance of CD1a expression by epidermal dendritic cells. The other GVHRs such as erythema exudativum multiforme (EEM), fixed drug eruption, toxic epidermal necrolysis (TEN) and lichen planus could not be separated. Our protocol of the immunopathologic examination could be done quickly (within 3 hours) and provides more detailed and useful information for the diagnosis of GVHD in early period compared with conventional histopathology.
 ...
PMID:[Differential diagnosis of post-transfusion graft-versus-host disease (GVHD) by rapid immunopathologic examination of the skin]. 930 Dec 87

Transfusion-associated graft-versus-host disease (TA-GVHD) in immunocompetent patients is mediated by activated lymphocytes derived from the donor directed against host allogeneic HLA antigens. When considering this pathogenesis, the target of TA -GVHD treatment should be focused on the cytotoxic T cells (CTL) directed against host HLA. The combination therapy of anti-CD3 monoclonal antibody, OKT3, cyclosporin A, and corticosteroid may be effective to inhibit the cytotoxic activity of CTL. In addition to these immunosuppressive agents, monoclonal antibodies against functional cell surface molecules, such as LFA-1, ICAM-1, Fas, and Fas ligand, must be effective for treatment of TA-GVHD. Since the effective standard therapy of TA -GVHD has not been established, the prevention by gamma irradiation of cellular blood components is most important.
 ...
PMID:[Treatment of transfusion-associated graft-versus-host disease]. 930 Dec 92


<< Previous 1 2 3 4 5 6 Next >>