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)

These studies examined the role of cytokines in chronic autoimmune graft-versus-host disease (GVHD) in B6D2F1 mice injected with lymphoid cells from DBA/2 mice. Anti-interleukin (IL)-4 and anti-interferon (IFN)-gamma mAb, or IFN-gamma, were used in vivo to modulate B cell hyperactivity and disease. Kinetic experiments showed that, 2-3 weeks after induction, GVH mice had 100x elevated serum IgE, while IgG1 and IgG2a were 10x above normal. Early treatment with anti-IL-4 mAb or IFN-gamma decreased serum IgE and IgG1 and had no effect on IgG2a. Anti-IFN-gamma mAb treatment increased serum IgE and IgG1 while reducing IgG2a. This increase in serum immunoglobulins could be correlated with an increased spontaneous secretion of IL-4, IL-5, and IL-6 in spleen cell cultures from anti-IFN-gamma mAb-treated GVH mice. While neither anti-IFN-gamma nor IFN-gamma treatments altered the disease course, anti-IL-4 treatment delayed proteinuria and death in GVH mice. These observations suggest an important role for IL-4 in immune complex-mediated glomerulonephritis in chronic GVHD.
 ...
PMID:Effects of in vivo administration of interferon (IFN)-gamma, anti-IFN-gamma, or anti-interleukin-4 monoclonal antibodies in chronic autoimmune graft-versus-host disease. 159 85

There is growing interest in studying pathways of mast cell activation. In a mouse model of chronic graft-vs-host disease (cGVHD) extensive mast cell activation and degranulation occurs in vivo coincident with the development of dermal fibrosis. An interesting feature of this model is that the mast cell reaction is slow to develop, occurring over a period of weeks and waning by 300 days. The aim of our work was to investigate the effects of supernatants from splenocytes of such cGVHD mice (cGVHD sups) on mouse and rat peritoneal mast cells cocultured with 3T3 skin fibroblasts. We found that cGVHD sups are able to release histamine from both mouse and rat cultured mast cells in a slow fashion. Histamine release became evident only after 5-8 days of coculture of the mast cells with the cGVHD supernatants and thereafter decreased to basal levels. Mast cell activation due to cGVHD supernatants was a noncytotoxic event as demonstrated by mast cell counts in the cocultures and by the ability of mast cells to exclude trypan blue. Mast cells that had been activated by incubation with the cGVHD sups were as responsive to stimulation with either anti-IgE antibodies or compound 48/80 as were mast cells incubated with control sups. Supernatants from mice early in GVHD (Days 11-28) were most active in promoting histamine release. Supernatants from spleens of mice which had GVHD for 290 days and where the mast cells had returned to full granulation in vivo were inactive. This is the first in vitro study demonstrating slow mast cell histamine release instituted by other cells, namely the splenocytes of cGVHD mice.
 ...
PMID:Histamine release from mouse and rat mast cells cultured with supernatants from chronic murine graft-vs-host splenocytes. 169 Jun 7

Immunoglobulin production, particularly IgE, is known to be dysregulated in graft-vs-host disease (GVHD). We examined serum levels of the highly T-dependent Ig isotypes, IgE, IgG1, and IgG2a, in two different mouse models of GVHD. GVHD across minor histocompatibility barriers is produced by injection of B10.D2 spleen cells into 600 rad irradiated BALB/c hosts. Both strains are H2d and mls b, but differ at the minor histocompatibility antigens. As GVHD progresses there is a rapid rise in serum IgE (300-fold) and IgG1 (2.5-fold) with a peak at Day 14. Concomitantly, IgG2a falls. Serum immunoglobulin levels return to normal by 11 weeks. The rise in IgE is abolished by increased (900 rad) recipient irradiation, suggesting that host-derived factors are important. GVHD across major histocompatibility barriers is produced by injection of DBA/2 spleen cells into unirradiated or 600 rad irradiated (B6 x DBA/2)F1 hosts. Only in the irradiated recipients is there severe Ig dysregulation. In this situation there is a 100-fold rise in IgE, and 5- to 10-fold rises in IgG1 and IgG2a. While the results in GVHD across minor barriers suggest stimulation of T helper cells secreting IL-4, the increase in IgE, IgG1, and IgG2a levels in GVHD across major barriers suggests activation of IL-4 and IFN-gamma-secreting T cells. These results indicate that different mechanisms may be operating in these two models of GVH. Murine GVHD can serve as a model for studying dysgammaglobulinemias in general and for hyper-IgE formation in particular.
 ...
PMID:Immunoglobulin dysregulation in murine graft-vs-host disease: a hyper-IgE syndrome. 235 59

Total serum IgE levels were followed in 135 bone marrow transplant recipients in order to determine the clinical significance of post-transplant serum IgE monitoring. Patients with IgE levels less than 60 U/ml at the time of bone marrow transplantation (BMT) (59%) experienced at least one IgE peak. Patients with pretransplant IgE levels greater than or equal to 60 U/ml (16%) showed decreasing values following BMT. In 19% of patients, IgE levels were low and did not change up to 3 months after BMT. Increase in IgE levels coincided in time with engraftment (p less than 0.01) and acute graft-versus-host disease (GVHD) (p less than 0.01). Early IgE peaks were also seen in patients without GVHD. Maximal IgE values did not differ during grades II-IV GVHD compared with grades 0-1, but two or more peaks were more common in patients with grades II-IV (p less than 0.001). IgE peaks also appeared in patients receiving T cell-depleted marrow without GVHD. Syngeneic bone marrow recipients had high IgE levels after BMT. Two patients had increasing IgE values following reconditioning and retransplantation, but booster grafts had no effect on IgE levels. IgE levels were not changed during septicemia, herpes simplex virus or cytomegalovirus infections, and chronic GVHD. No linear correlation was found between serum IgE levels and CD4+/CD8+ ratios, percentages, or absolute numbers of either group of cells. It was concluded that serum IgE elevation is found in association with engraftment and acute GVHD, but is mainly caused by the conditioning treatment.
 ...
PMID:Serum IgE levels after bone marrow transplantation. 265 11

We report four cases of Omenn's syndrome (OS), an autosomal recessive disease characterized by early erythrodermia, protracted diarrhea, severe infections, lymphadenopathy, hepatosplenomegaly, failure to thrive, and leukocytosis with marked eosinophilia. The immunological investigations revealed B lymphopenia with increased levels of serum IgE and marked depression of T-cell activation, not restored by the addition of exogenous interleukin 2 (IL-2). IL-2 and interferon-gamma (IFN-gamma) production in vitro were very low or absent. One patient was treated with HLA-identical bone marrow transplant with a complete remission of the clinical picture and the immunological defect. The infant died of graft versus host disease 4 months after the graft. For the remaining three infants the outcome was also fatal within the first year of life. In conclusion, OS should be considered a severe combined immunodeficiency disease with peculiar clinical, immunological, and histological findings.
 ...
PMID:Clinical and immunological findings in four infants with Omenn's syndrome: a form of severe combined immunodeficiency with phenotypically normal T cells, elevated IgE, and eosinophilia. 311 64

Mast cells are in close contact with other cells in neurofibromatosis, e.g. neural cells and fibroblasts. Secretory products of mast cells may be important in the regulation of collagen synthesis by fibroblasts and Schwann cells. Newer methods of detecting mast cells by avidin staining of granules and localization of membrane Fc receptors for IgE have been exploited in at least one experimental model of fibrosis (murine chronic graft-versus-host disease). Such approaches should help in understanding parameters involved in modulation of cell growth in neurofibromas. Future directions for the study of cellular dynamics in neurofibromas should include detection of activated (degranulated) mast cells, Schwann cells and effects of mast cell products on collagen gene expression.
 ...
PMID:Mast cells and neurofibromatosis. 315 31

Serum IgE levels were followed longitudinally twice a week for up to 100 days in 60 children treated for leukemia, severe aplastic anemia or severe combined immunodeficiency: 52 underwent allogeneic bone-marrow transplantation and 8 immunosuppressive treatment. In 55 of 58 treatment periods which could be analyzed (95%), a transient sharp increase of serum IgE was detected, irrespective of the initial diagnosis and mode of treatment. A second IgE peak was recorded in 16% of evaluable treatment periods. In the transplanted leukemia and aplastic anemia patients, the rise of serum IgE levels occurred at the same time, i.e. at a mean of 14 days after transplantation; it occurred significantly later in children grafted for severe combined immunodeficiency. In children who received immunosuppression for the treatment of severe aplastic anemia, IgE elevations were always seen within 2 weeks after institution of therapy. No relation was found between either the occurrence of clinically acute graft-versus-host disease or infections after treatment, and the time of onset of IgE elevations. It is suggested that the phenomenon of IgE peaks in the population of patients investigated was due to disturbance of T-cell regulation, i.e. a temporary impairment of T-suppressor cell activity.
 ...
PMID:Transient elevation of serum IgE after allogeneic bone-marrow transplantation. 330 75

Fever after bone marrow transplantation may indicate the onset of bacterial or opportunistic infection, or acute graft-versus-host disease (GVHD). In an attempt to differentiate between infection and GVHD, we prospectively studied 41 bone marrow transplants in 38 patients (24 allogeneic, 17 autologous). Elevation of C-reactive protein (CRP) proved to be a good indicator of disseminated infections. In 40 episodes of documented (11) or presumed (29) sepsis, CRP rose above 5 mg/dl in 38 episodes (95%), and above 10 mg/dl in 32 episodes (80%). The CRP concentration paralleled the clinical course of the infectious episodes. Elevated CRP values were not observed in the 15 episodes of acute GVHD without concurrent infection. High peak values of serum total IgE, ranging from 4-fold to over 4000-fold baseline, were observed posttransplant in 18/22 allogeneic BMT recipients, temporally associated with activation of acute GVHD. IgE was elevated neither in episodes of sepsis without concurrent GVHD, nor in viral or focal bacterial infections. In general, septic infections were characterized by high CRP but low IgE levels. Acute GVHD without concurrent infection was characterized by high IgE but low CRP. We conclude that CRP and serum total IgE utilized together in serial fashion are helpful in distinguishing sepsis from acute GVHD.
 ...
PMID:Differentiation of presumed sepsis from acute graft-versus-host disease by C-reactive protein and serum total IgE in bone marrow transplant recipients. 331 43

After conventional bone marrow transplantation serum IgG, IgM and IgA levels fall from pre-transplant levels and may not return to normal for 3-12 months. In contrast IgE may rise to supranormal levels, an event that may be associated with graft-versus-host disease. We have investigated the recovery of immunoglobulin isotypes in the recipients of allogeneic marrows depleted of T-cells to prevent graft-versus-host disease. We find that pre-transplant IgG, IgM and IgA levels are maintained throughout the post-transplant period but that there is a short-lived rise in IgE about 3 weeks after transplantation: this rise occurs in the absence of clinically detectable graft-versus-host disease. We conclude that specific T-cell depletion does not impair and may actually enhance the functional recovery of B cells after allogeneic BMT.
 ...
PMID:Recovery of immunoglobulin isotypes following T-cell depleted allogeneic bone marrow transplantation. 353 Mar 13

A patient with acute lymphoblastic leukaemia in first remission received a bone marrow transplant from his HLA-identical brother. The patient had a remote history of asthma and the bone marrow donor had allergic asthma. The patient developed acute graft-versus-host disease and died 2 months after transplantation. At autopsy there were high numbers of plasma cells in lymphoid tissues. The majority of this cell population was of polytypic IgG, IgM or IgA origin, but there was a significant contribution by monotypic IgE-lambda-containing cells, varying from 10% in the appendix to 35% in lymph node. The serum IgE level in the patient was less than 0.5 IU/ml before transplantation, and 8.5 IU/ml 1 month thereafter. In the donor the value was about 400 IU/ml. In the donor only, specific IgE antibodies to various allergens were detectable. The bone marrow of the donor contained 0.4% plasma cells, of which 36% were IgE positive (chi/lambda ratio 1/11). These findings are compatible with literature data on elevations in serum IgE level following bone marrow transplantation. We suggest that the IgE-lambda plasma cell population is of donor origin.
 ...
PMID:Monotypic immunoglobulin E plasma cells in an allogeneic bone marrow transplant recipient. 353 16


1 2 3 4 5 Next >>