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)

Acute GVHD was induced in unirradiated (DA x LEW)F1 rats by the injection of parental DA lymphoid cells. Serum sequentially derived from such animals was found to contain increased levels of antibodies reactive with 70-kDa heat-shock protein (hsp70). Elevated levels of antibody to hsp70 were detected as early as 7 days and were maximal 14 days after the induction of GVHD. These increased levels of antibodies reactive with hsp70 paralleled the onset of the signs and symptoms associated with the development of GVHD. Increased anti-hsp70 reactivity in GVHD sera was associated statistically with increased levels of hsp70-reactive IgM, IgG2a, and IgG2b. In addition, GVHD sera reacted with a 70-kDa protein found within (DA x LEW)F1 lymphoid tissue. These results demonstrate that increased levels of antibodies to hsp70 parallel the onset and development of GVHD in an acute model and are the first to show that antibodies reactive with hsp70 are associated with an ongoing disease process.
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PMID:Antibodies specific for the 70-kDa heat-shock protein parallel the development of acute graft-versus-host disease in (DA x LEW)F1 rats. 770 72

Chronic graft-versus-host disease (GVHD) was induced in female (C57 B10S/DBA/2)F1 hybrid mice with two successive injections of lymphoid cells from parental DBA/2 strain. Serial bleedings of 27 GVHD mice were screened with a panel of antigens including the five histones H1, H2A, H2B, H3 and H4, 15 histone peptides, core particles, dsDNA, heat-shock proteins hsp70 and ubiquitin, a branched peptide of ubiquitinated H2A (U-H2A), poly(ADP-ribose) and SSB/La protein. The predominant IgG response to histone peptides was directed against regions 204-218 of H1, 1-25 of H2B and 1-29 of H4. GVHD mice also produced IgG antibodies to dsDNA and chromatin core particles as reported previously. IgG antibodies reacting with dsDNA appeared before antibodies to core particles and histones. Raised levels of antibodies to U-H2A, but not to monomeric ubiquitin, were also found. While the level of antibodies to dsDNA, histones and core particles decreased significantly before the appearance of proteinuria, suggesting their involvement in glomerular injury, the longitudinal pattern of anti-U-H2A peptide response was apparently not linked to the manifestation of lupus nephritis in GVHD mice.
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PMID:Antibodies to DNA, chromatin core particles and histones in mice with graft-versus-host disease and their involvement in glomerular injury. 795 35

Acute lethal graft-versus-host disease (GVHD) was induced in unirradiated (LEW x DA)F1 rats by injection of DA parental lymphoid cells. Control rats received the same dose of (LEW x DA)F1 cells. The level of hsp70 at different stages of GVHD was examined in the spleen, lymph nodes, thymus, liver, lung, kidney, heart, and skeletal muscles of GVHD and control animals. Hsp70 was present in all organs analyzed in both groups and, with the exception of the spleen and lymph nodes, detectable levels remained constant during the disease. However, the spleen and lymph nodes of GVHD rats showed distinct changes in the hsp70 levels throughout the course of the disease. Expression of hsp70 in spleen and lymph nodes was augmented 7 and 14 days after induction of the disease. During the last stages of GVHD, 18-21 days after the induction, expression of hsp70 diminished to a level similar to that in untreated and control animals. Elevated levels of hsp70 in lymphoid organs during GVHD suggest an involvement of hsp70 in the pathology of the disease.
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PMID:Expression of 70-kDa heat-shock protein during acute graft-versus-host disease. 955 58

We have shown previously that increased levels of hsp70, and antibodies reactive with hsp70 parallel the onset and severity of graft-versus-host disease (GVHD) in a parent --> (DA x LEW)F1 rat model. In this study we have assessed the effect of reducing the levels of the 70 kDa heat shock protein (hsp70), on the morbidity and mortality of acute GVHD in (DA x LEW)F1 rats. The reduction was accomplished by the administration of 15-deoxyspergualin (DSG), an immunosuppressive agent which binds to a constitutively expressed member of the 70 kDa heat shock protein family. DSG administered via three different protocols reduced GVHD-associated morbidity. One of the regimens, which consisted of intermittent DSG administration, also significantly reduced GVHD associated mortality. This DSG treatment reduced hsp70 levels in spleen and lymph nodes, inhibited anti-hsp70 antibody production, and diminished the serum levels of IL-2, IFN-gamma, TNF-alpha, and IL-10. IL-4 levels in the serum did not change during GVHD and were not effected by DSG. These results show that the mechanism of DSG immunosuppressive effect in rat GVHD may involve DSG's capacity to bind to hsp70, which in turn may lead to a decrease in levels of circulating anti-hsp70 antibodies, and reduced production of cytokines.
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PMID:Reduced levels of Hsp70 result in a therapeutic effect of 15-deoxyspergualin on acute graft-versus-host disease in (DA x LEW)F1 rats. 1104 61

The development of graft-versus-host disease (GVHD) can be modified by non-MHC factors. Based on our previous studies that showed an involvement of 70kD heat shock protein (hsp70) in the pathology of acute GVHD in a rat model, we determined serum levels of antibodies to hsp70, hsp90 and hsp60 in human recipients after allogeneic peripheral blood stem cell transplantation (PBSCT). Serum levels of these antibodies were correlated with GVHD status in the recipients. Twenty-nine recipients with high-risk haematological malignances, who received G-CSF mobilized allogeneic PBSCT from HLA matched family donors, were evaluated between 30 and 960 days after transplantation. Two recipients had no GVHD, 18 developed acute followed by chronic GVHD and nine developed only chronic GVHD. Patients with acute GVHD had a significant increase in IgM anti-hsp70 and/or anti-hsp90 early (30-90 days) after transplantation. In addition, an increase in IgM anti-hsp70 and/or anti-hsp90 antibodies preceded or accompanied chronic GVHD. Antibody levels returned to normal within the next 400 days in the majority of patients. Anti-hsp60 antibody levels were not different from control levels regardless of GVHD status. This study implies that the development of acute and/or chronic GVHD in humans is accompanied by an increase in anti-hsp70 and anti-hsp90 antibodies. Monitoring levels of anti-hsp70 and anti-hsp90 antibodies in stem cell transplant recipients may serve as a diagnostic tool and help to predict the onset of GVHD.
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PMID:Antibodies to 70 kD and 90 kD heat shock proteins are associated with graft-versus-host disease in peripheral blood stem cell transplant recipients. 1196 75

GVHD is a major complication after allogeneic SCT. Etiology of GVHD is multifactorial. Known role of hSPS in antigen presentation could suggest their potential role in the alloreactive process that leads to aGVHD. HSPS represent major immunodominant antigens in a wide spectrum of microbial pathogens. Bacterial and fungal colonization, infection and sepsis are frequent in immunocompromised patients with various malignant and non-malignant diseases. We studied PBMC responses to recombinant human hsp60 (rh-hsp60), rh-hsp70 and Mycobacterium bovis hsp65 (M. bovis hsp65) in relation to aGVHD and infection in 34 pediatric patients with various lympho-hemopoietic malignancies as well as non-malignant disorders subjected to SCT. PBMC of patients before initiation of preparative regimen as well as after engraftment were stimulated with hSPS (1 microg/mL/well, 7-day cultivation). PHA was used as a control of the stimulation ability. Cell responses were measured after the incorporation of 3H-thymidin (pulsing with 1 microCi/well) and were expressed as stimulation indexes (SI). We demonstrated significantly high proliferative response to rh-hsp60 as well as M. bovis hsp65 in a cohort of pretransplant patients with anamnestic and/or actual infection when compared with a cohort of patients without infection and healthy individuals. Strong PBMC cell responses to hSPS were found in patients who were at present colonized with Escherichia coli and Klebsiella pneumoniae or had previously K. pneumoniae infection with subsequent sepsis. Our findings support various studies dealing with immunodominant hSPS in connection with several pathogens and infectious diseases. Although no statistical difference for proliferative response to PHA was observed, PBMC responses against all tested hSPS comparing a cohort of patients with aGVHD and that with no sign of GVHD resulted in significantly lower SI for all tested hSPS in patients with aGVHD. Lower stimulation with hSPS during aGVHD might be explained by the stress-induced upregulation of self-hSPS synthesis that might lead to the inhibition of self-hSPS reactive T-cell response. Vice versa, we hypothesize that increased hsp-specific stimulation may reflect the presence of protecting regulatory T cells preventing the development of Th1-mediated diseases involving aGVHD.
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PMID:Peripheral blood mononuclear cell responses to heat shock proteins in patients undergoing stem cell transplantation. 1657 4