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)

The antigenic status of the preimplantation embryo is ill-defined and there are no clearly recognized maternal immune reactions against this early stage of development. Following implantation, the pregnant female shows evidence of immune recognition of her intrauterine allogeneic conceptus. In a proportion of pregnancies, particularly in multiparous women, there are maternal cytotoxic antibodies exhibiting specificity for the paternally inherited HLA antigens of the fetus. When these are undetectable there may be other antibodies that are non-complement fixing and non-cytotoxic or antibodies that are not present as free molecules and incapable of identification in conventional assays. Anti-HLA antibodies pose no threat to the fetus, principally owing to their absorption by the placenta and, very likely, the harmless binding of any that do reach the fetal circulation. No potentially deleterious cytotoxic T lymphocyte generation occurs in most pregnancies. The extent to which this is due to maternal immunoregulatory control processes is not yet established. The fetal trophoblast is able to act as a protective barrier by virtue of unique properties, including a lack of conventional class I and class II HLA molecules, that render it insusceptible to immune attack. The nature and significance of any maternal recognition of non-HLA antigens on trophoblast await elucidation. Maternal immune cell traffic across the placenta occurs only at a very low level, if at all, in normal pregnancy. This may take place to a greater degree in some of the rare instances of fetal graft-versus-host disease, but this is complicated by the associated fetal immunodeficiency. Maternal IgG antibodies are transmitted across the placental trophoblast by receptor-dependent mechanisms to provide immediate protection for the neonate against environmental pathogens. Leakage of fetal erythrocytes, leukocytes and platelets into the maternal circulation can elicit IgG isoantibodies that take advantage of the same mechanisms to gain access to the fetus, with pathological consequences. Autoantibodies in women with various disease states may similarly pass into the fetus but these normally produce only mild and transient effects. The development of the fetal immune system begins at an early stage of gestation. It is competent to respond to intrauterine infections from as early as 12 weeks and has full functional potential at birth. Maternally acquired IgG is available for up to 9 months of life until the infant's own immune system has been adequately primed and activated following first exposure to specific antigens. The normal fetomaternal immune relationship represents a remarkable harmonious association between two genetically disparate individuals.(ABSTRACT TRUNCATED AT 400 WORDS)
Baillieres Clin Obstet Gynaecol 1992 Sep
PMID:The normal fetomaternal immune relationship. 144 16

Transfer of fetal red blood cells and platelets to the maternal circulation can stimulate an immune response with production of immunoglobulin that can cross the placenta. Similarly, passage of maternal stem cells to an immunologically incompetent fetus can theoretically produce graft-versus-host disease. disease. Maternal sensitization to red blood cell antigens such as D and Kell can result in anaemia, hydrops, and death in an incompatible fetus. Current assessment of these pregnancies involves serial analysis of amniotic fluid bilirubin concentration, with umbilical cord blood sampling reserved for special circumstances; neither ultrasound or Doppler blood flow analysis are accurate in the prediction of fetal haematocrit. Intravascular transfusion is the treatment of choice for hydropic fetuses. Perinatal survival in non-hydropic fetuses is similar with either intravascular or intraperitoneal transfusion, and the choice of procedures is individualized. Isoimmune fetal thrombocytopenia is usually the result of maternal sensitization to the PlA1 antigen. There is significant risk of intracranial haemorrhage, both antepartum and during labour and delivery. Umbilical cord blood sampling at term can determine fetal platelet count and the need for platelet transfusion, and can aid in deciding the appropriate route of delivery.
Baillieres Clin Obstet Gynaecol 1992 Sep
PMID:Alloimmune conditions and pregnancy. 144 20

Over the last 20 years allogeneic bone marrow transplantation from an HLA-identical sibling donor has become the treatment of choice for a number of human haematological malignancies, severe aplastic anaemia, some congenital diseases of the immune and haemopoietic systems, and some inborn errors of metabolism. Recently, the successful introduction of HLA-matched unrelated donor transplants, convenient T cell depletion technology, combination immunosuppressive therapy to minimise graft-versus-host disease, blood products that are seronegative for cytomegalovirus, effective antiviral agents, and cloned haemopoietic and immune system growth factors have markedly increased the scope of bone marrow transplantation. Additionally, autologous transplantation appears to have promise especially in lymphoma and breast cancer.
Med J Aust 1992 Sep 21
PMID:Bone marrow transplantation. 144 94

We searched for evidence that immunodeficiency in graft-versus-host disease (GVHD) is in part due to alloimmune damage to lymph nodes. We used immunoperoxidase techniques to stain T-cell subsets, pan-B cells, and follicular dendritic reticular cells (FDRC) in frozen sections of lymph nodes from 80 marrow graft recipients (56 with GVHD, 11 autografts, and 13 allografts without GVHD). We found that 46% of the GVHD patients had reversed CD4:CD8 ratios and only 13% of non-GVHD patients had such disturbed ratios (p = 0.006). Pan-B (CD22) cell labeling was present in the follicular regions of 73% of patients without GVHD and only 53% of patients with GVHD (p = 0.05). Focal FDRC staining was geographically concordant with clusters of B cells in 88% of cases (p less than 10(-7)). These data confirm that disturbed intranodal CD4:CD8 ratios are present more frequently in GVHD patients than in non-GVHD patients or in autografted patients. They suggest more delayed follicular B-cell reconstitution in GVHD patients. They show an extremely tight association of FDRC with clusters of B cells in the recovering lymph node, as in the developing fetal node. We hypothesize that the lack of follicular dendritic cells may contribute to dysfunctional B-cell maturation by ablating orderly antigen presentation and clonal expansion in the lymph node cortex.
Exp Hematol 1992 Sep
PMID:Abnormal CD4:CD8 ratios and delayed germinal center reconstitution in lymph nodes of human graft recipients with graft-versus-host disease (GVHD): an immunohistological study. 150 36

Early trials of allogeneic marrow transplantation for homozygous thalassemia were disappointing in patients older than 16, with four of six patients dying early of graft-versus-host disease-related complications, one patient dying at 9 months of infection due to graft failure, and one dying at 6 years of recurrent thalassemia. Three classes of risk could be identified in analyses of results of transplantation in younger patients using the criteria of degree of hepatomegaly, the presence or absence of portal fibrosis, and a history of adequate or inadequate chelation therapy. Patients for whom all three criteria were adverse constituted a very high risk group (class 3) for marrow transplantation. On the basis of these analyses, a conditioning regimen was designed that yielded superior results for class 3 patients under 17 years of age. Most patients older than 16 years presenting for transplantation have disease characteristics that place them in class 3 and, because of the improved results with the new class 3 regimen in younger patients, a study was designed to treat patients older than 16 years using treatment regimens assigned on the basis of disease class. Twenty patients were treated using this protocol and, with a minimum follow-up of 9 months, there have been three early deaths, one patient has recurrent thalassemia, and 16 patients are alive disease-free. The actuarial probabilities of survival, disease-free survival, and rejection are 0.85, 0.80, and 0.05, respectively, with a survival plateau extending from 6 months to 3 years. Marrow transplantation is a reasonable option for adults with progressive thalassemia who have suitable donors.
Blood 1992 Sep 15
PMID:Bone marrow transplantation in adult thalassemia. 152 Aug 85

Intravenous immunoglobulin (IVIG) has several potential uses in bone marrow transplantation. Most often IVIG is used to modify cytomegalovirus (CMV) infection or CMV-related interstitial pneumonia. It also is used to modify graft versus host disease (GVHD) and decrease infections other than CMV. Another use is to treat autoimmune complications of bone marrow transplants. The data are reviewed indicating that IVIG decreases CMV-related interstitial pneumonia. Part of this efficacy may be a direct antiviral effect; decreasing GVHD and modifying the immune response to CMV-infected lung cells also may be important. Some studies suggest that IVIG and ganciclovir are effective therapy of CMV-related interstitial pneumonia. Results suggesting that IVIG administration decreases infections other than CMV are less convincing. There is little information regarding IVIG therapy of autoimmune transplant complications. These uses of IVIG are reviewed in the context of other potential interventions, and future research directions are defined.
Cancer 1991 Sep 15
PMID:Intravenous immunoglobulin in bone marrow transplantation. 165 50

Ganciclovir was given prophylactically to 25 patients receiving allogeneic bone marrow transplants for haematological malignancy. Patients who were seropositive for cytomegalovirus (CMV) pre-transplant were given ganciclovir both pre- and post-transplant. Those who were CMV seronegative, but who received marrow from a CMV seropositive donor, received ganciclovir post-transplant. No nonhaemopoietic toxicity was observed. Toxicity was restricted to late reversible haematological toxicity in four of the 19 evaluable patients (one thrombocytopenia, one pancytopenia, two leucopenia). No CMV interstitial pneumonitis (IP) was observed, nor were any other clinically manifest CMV infections detected. Sixteen patients remain alive at greater than 84 to greater than 518 d post-transplant. In a retrospective comparison of 152 recipients of allogeneic transplants for haematological malignancy not given prophylactic ganciclovir, and in whom either the recipient or the donor or both were CMV seropositive, the incidence of all clinically manifest CMV infections was 23% (P = 0.02) and that of CMV IP 17% (P = 0.05). If only patients in the study group and the control group receiving the same cyclosporin/short methotrexate prophylactic immune suppressive regimen, the same prophylactic acyclovir regimen and the same CMV and leucocyte-filtered blood product transfusion strategy were considered, the incidence of all clinically manifest CMV infections in the control group was 24% (P = 0.01) and that of CMV IP 13% (P = 0.07). Ganciclovir appears to reduce the incidence of CMV infections in allogeneic marrow transplant recipients even in those given immune suppressive regimens associated with adequate control of acute graft-versus-host disease.
Br J Haematol 1991 Sep
PMID:Prophylactic use of ganciclovir in allogeneic bone marrow transplantation: absence of clinical cytomegalovirus infection. 165 94

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) secreted by a hepatoma cell line, HA22T/GVH, was purified and assessed for its effects in vivo on blood leukocytes and bone marrow granulocyte-macrophage progenitor cells (CFU-GM) in ICR mice pretreated with a sublethal dose of cyclophosphamide (cytoxan). The hGM-CSF preparations were natural and had no detectable endotoxin. Five days after the administration of 300 mg/kg cytoxan, severe leukopenia with marked myelopoietic suppression was induced. The cytoxan-treated mice were then injected intraperitoneally with 10,000 units of purified hGM-CSF/mouse daily for three days. Leukopenia was totally abrogated and the leukocyte number greatly increased to a level 2- to 3-fold higher than in GM-CSF-uninjected mice. Differential white cell count showed that the subpopulations of leukocytes responsive to hGM-CSF stimulation were mainly of neutrophils and monocytes, while the lymphocytes remained unaffected. Meanwhile, in the bone marrow, hGM-CSF administration induced an apparent (3-fold) increase in the number of myeloid progenitor cells, CFU-GM. However, the effect in vivo of a single hGM-CSF injection could only maintain for 48 hrs. In addition, the loss in body weight caused by cytoxan was less in the mice with subsequent hGM-CSF than those without CSF. These results suggest that injection of GM-CSF can effectively reconstitute the cytotoxic drug-damaged myelopoiesis without apparent in vivo toxic reaction.
Zhonghua Yi Xue Za Zhi (Taipei) 1991 Sep
PMID:In vivo stimulation of myelopoiesis in cyclophosphamide-treated mice by purified human GM-CSF. 165 33

Twenty-nine patients with advanced leukemias (median age 34 years) received histocompatible sibling marrow that had been depleted of T cells by ex vivo incubation with anti-CD5 monoclonal antibody-ricin immunotoxin (T101-R) for the purpose of graft-versus-host disease prophylaxis. Donor cell engraftment was documented in 28/29 patients by DNA restriction fragment length polymorphisms. In this pilot study the dose of T101-R incubated with donor marrow was increased in a stepwise manner from 300 ng (10 patients) to 600 ng (5 patients) to 1000 ng immunotoxin (IT)/10(7) bone marrow mononuclear cells (14 patients) in an attempt to achieve more effective GvHD prophylaxis. A statistically significant reduction in acute GvHD was achieved for patients receiving marrow pretreated with 1000 ng of immunotoxin (34%) compared to recipients of BM treated with 300 ng immunotoxin (100%, P = 0.0004). T-depleted marrow samples were evaluated for residual T cell activity using several in vitro assays including proliferation to the purified mitogen PHA (HA-17) and in mixed lymphocyte culture (MLC), T cell cytotoxicity, a limiting dilution assay for detecting precursors of proliferating T cells (LDApPTL), and phenotypic analysis of viable T cells expanded in 16-day culture with interleukin 2. The extent of T cell depletion determined by LDA assay varied widely at each immunotoxin concentration used. Thus, there was no correlation between the dose of T cells infused and subsequent GvHD. Phenotyping of lymphocytes recovered from immunotoxin-treated marrow demonstrated that residual T cells were CD5 negative in all cases tested. The only in vitro parameter that predicted subsequent acute or chronic GvHD was the demonstration of viable CD5 negative lymphocytes with T cell phenotype (CD2, CD3, and/or CD7 positive) after 16-day culture with IL-2 of the T-depleted bone marrow. We observed that such CD5 negative cells expressing other T cell markers have cytotoxic function and speculate that these cells may be capable of mediating GvHD in allogeneic transplantation.
Transplantation 1990 Sep
PMID:T cell depletion with anti-CD5 immunotoxin in histocompatible bone marrow transplantation. The correlation between residual CD5 negative T cells and subsequent graft-versus-host disease. 169 19

The levels of alpha-1 microglobulin (alpha 1m) and beta-2 microglobulin (beta 2m) in serum were estimated in 77 bone marrow transplant recipients. In comparison to pre-transplant levels, the highest levels of alpha 1m and beta 2m were found during impairment of renal function, i.e., during cyclosporin-induced nephrotoxicity and during treatment with other nephrotoxic drugs (P less than 0.001). The alpha 1m levels were less elevated during infections and acute graft-versus-host disease (P less than 0.01), while beta 2m levels were markedly elevated during the same conditions (P less than 0.001). The linear correlations between serum creatinine and alpha 1m and creatinine and beta 2m were r = 0.7 and 0.8, respectively (P less than 0.001). The overall correlation between alpha 1m and beta 2m was 0.4 (P less than 0.001). It is concluded that alpha 1m might be a complement to serum creatinine levels in monitoring renal function after bone marrow transplantation.
Transpl Int 1991 Sep
PMID:Serum levels of alpha-1 microglobulin and beta-2 microglobulin in bone marrow transplant recipients treated with cyclosporin A. 172 Mar 17


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