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 antigens are the major barrier to successful transplantation. Three of the seven heterodimers (HLA-A, -B, and -DR) contribute most to the immunogenicity of a mismatched organ. Although classical serology has been used in the past to phenotype donors and recipients, histocompatibility laboratories are increasingly turning to DNA-based methods to directly genotype patients and donors for the alleles of the HLA complex. Some methods are still evolving, while several others are established well enough to use in the clinical laboratory. The application to solid organ transplantation will result in greater accuracy and a better correlation between HLA matching and graft survival in the future. In fields such as bone marrow transplantation, where matching is critically important for prevention of graft-versus-host disease and engraftment, molecular HLA testing is already being mandated by the transplantation community.
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PMID:HLA molecular typing. 792 29

Materno-fetal GVHD is commonly a fatal condition occurring in patients with severe combined immunodeficiency (SCID). Definitive diagnosis is often difficult. We describe a patient with clinical features suggestive of materno-fetal GVHD but in whom histology was atypical. Y chromosome-specific PCR amplification analysis of DNA extracted from the skin biopsy was performed to detect chimeric evidence of infiltrating maternal T cells. This revealed strong positivity for the Y chromosome, indicating lack of maternal T cell engraftment and thus confirming a diagnosis of Omenn's syndrome, a variant of SCID in which atypical lymphocyte clones give rise to a similar picture. In contrast, Y chromosome-specific PCR analysis of skin biopsy DNA from a male patient with a rash clinically and histologically typical of materno-fetal GVHD revealed absence of the Y chromosome, indicating infiltration of maternal cells and thus confirming the diagnosis of materno-fetal GVHD. Y chromosome-specific PCR analysis is thus a useful investigation for the differentiation of materno-fetal GVHD from Omenn's syndrome in pre-BMT SCID patients presenting with unexplained rash.
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PMID:Differentiation of materno-fetal GVHD from Omenn's syndrome in pre-BMT patients with severe combined immunodeficiency. 795 Nov 6

The aim of this study was to evaluate immunological characteristics of human fetal liver (FL) cells, fresh and cryopreserved, 7-12 weeks post-conception. With monoclonal antibodies, HLA-associated determinants were demonstrated on FL. Although serological HLA determination of A, B, C and class II antigens was not possible, genomic HLA class II typing using RFLP technique or PCR amplification with sequence-specific primers was feasible. MLC induced only minor responses. Exposure to standard mitogens and polyclonal B cell activators did not stimulate DNA synthesis or antibody production. ABO antigens were expressed and determined. The apparent low immunological capacity of FL cells may reduce the risk of rejection and graft-versus-host disease when such cells are used in transplantation.
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PMID:Immunological capacity of human fetal liver cells. 795 Nov 26

It is now possible to access more than 1 million HLA-A, B typed volunteers willing to donate marrow. A preliminary search through the U.S. NMDP provides direct computerized access to the HLA-A, B, DR phenotypes of more than 186,000 registered donors. Fifty-one percent of preliminary searches yield at least one HLA-A, B, DR match, but a disproportional number of successful searches benefit primarily patients of Caucasian origin. Substantially greater recruitment among different racial and ethnic groups must occur if non-Caucasians are to have a better chance of finding an HLA-matched donor. Improved cooperation between registries and transplant networks in different countries remains an important goal. The optimal application of URD transplants may not be possible until an efficient and reliable worldwide marrow donor program has been established. DNA typing and matching for HLA alleles improves the timeliness of the donor search process and the precision of donor selection. HLA mismatching increases the probability and severity of GVHD, but minor mismatches for one HLA-A, B, or D/DRB1 locus does not appear to decrease survival. Although the risk of GVHD in URD transplants remains high and survival currently is not as favorable as HLA identical sibling transplants, better supportive care and GVHD control are providing a gradual improvement in the long-term disease-free survival of URD transplants.
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PMID:Marrow transplants from unrelated donors. 803 96

A 72-year-old woman with multiple recurrence of gallbladder cancer was treated by intrahepatic-arterial infusion of doxorubicin using an extracorporeal system of direct hemoperfusion with venovenous bypass. During this treatment, the patient received 600 ml of fresh whole blood and 30 units of platelet concentrate from five unrelated donors. Thereafter, high fever, skin rash over the whole body, and watery diarrhea developed, followed by leukopenia progressing to a fatal sepsis. Post-transfusion graft-versus-host disease (PT-GVHD) was suspected by the clinical manifestations and postmortem pathologic findings. To establish the diagnosis of PT-GVHD, polymerase chain reaction (PCR) amplification of DNA polymorphism associated with length variation in dinucleotide or trinucleotide microsatellite repeats at the loci of D6S89, int-2 protooncogene, and human growth factor with each of the different primer sets was performed using DNA from blood drawn from the patient with clinically established PT-GVHD of a donor origin and formalin-fixed pancreas of recipient origin. Genetic analysis revealed the changes in the patient's lymphocytes from that of the patient to that of donor origin. The present finding that formalin-fixed tissues can be used as a material of patient origin may contribute to accurate diagnosis of PT-GVHD after autopsy.
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PMID:Diagnosis of post-transfusion graft-versus-host disease after formalin-fixation. 808 23

We assessed the origin of peripheral blood cells and bone marrow cells obtained from 15 patients after allogeneic bone marrow transplantation (allo BMT) by sensitive two-step polymerase chain reaction (PCR) amplification of MCT118, a variable number of tandem repeats regions (VNTR), that can be used to detect the DNA pattern of a minor cell population of only 1% without using radioisotopes. Mixed chimerism(MC) was detected in the haematopoietic cells of 3 patients. Two patients developed relapse of leukaemia after the detection of MC and one patient died of bone marrow hypoplasia 7 months after BMT. These findings indicate the clinical usefulness of this method to monitor patients with MC. Also, we analyzed cytokine gene expression in peripheral blood mononuclear cells during the development of graft-versus-host disease (GVHD) in patients who underwent allo BMT using a semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The expression of interleukin(IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha mRNA was increased during the development of GVHD and the degree of this increment depended on the severity of the disease. These findings suggest that IL-1 beta, IL-6, and TNF-alpha produced by peripheral blood mononuclear cells play an important role in the development of GVHD. Therefore, analysis of MC and cytokine mRNA expression using the PCR technique after allogeneic bone marrow transplantation provide important information for treatment and monitoring of marrow transplant patients.
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PMID:[Clinical application of gene technology to monitor bone marrow transplantation]. 815 60

To evaluate the potential role of human herpesvirus type 6 (HHV-6) infection in patients after bone marrow transplantation (BMT) we sequentially analyzed buffy coat leukocytes, oral lavage fluid, and urine from 57 patients for the presence of HHV-6 DNA by polymerase chain reaction (PCR) before and after 60 BMTs. Twenty-four patients undergoing autologous BMT and 36 with allogeneic BMT were studied. Thirty-six patients (60%) were PCR positive in one or more tests. The majority of PCR-positive patients had positive results only sporadically, in 1 (n = 23) or 2 weeks (n = 5). Six patients were positive in 3 to 5 weeks. In 2 patients, we found a high frequency of positive tests, in 7 of 7 and 10 of 10 weeks analyzed. Twenty-four patients (40%) remained PCR negative throughout the post-BMT period. There was a significant correlation between the results of HHV-6 PCR and the occurrence of acute graft-versus-host disease (aGVHD). In grade II-IV, 6 of 8 (75%) patients had 2 or more positive PCR tests, compared with 5 of 25 (20%) patients without or with grade I aGVHD (P = .01). There was no difference in the outcome of PCR tests with respect to the type of BMT or pre-BMT HHV-6 enzyme-linked immunosorbent assay titers. Restriction enzyme analysis of PCR amplificates from 18 patients showed HHV-6 variant B in 16 (88.9%) and variant A in 2 cases (11.1%). We conclude that HHV-6 DNA can be detected in 60% of the patients after BMT. HHV-6 DNA can be detected more frequently in patients with moderate and severe aGVHD than in patients without aGVHD or with mild aGVHD.
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PMID:Herpesvirus type 6 in patients undergoing bone marrow transplantation: serologic features and detection by polymerase chain reaction. 818 Apr 2

Natural suppressor (NS) activity is detected in tissues undergoing intense hematopoietic regeneration. This includes the spleens of mice recovering from total lymphoid irradiation or cyclophosphamide treatment, or after induction of chronic graft-versus-host disease against minor histocompatibility antigens. NS cells are thought to act via an antiproliferative mechanism, based on the observation that NS cells inhibit thymidine ([3H]TdR) uptake by mitogen- or antigen-activated lymphocytes. In the present study, the mechanism of B cell inhibition by NS activity present in normal adult bone marrow is analyzed. [3H]TdR uptake of LPS-stimulated B cells is inhibited by the presence of bone marrow cells (BMC). Consistent with the decrease in DNA synthesis, cell cycle analysis reveals that the majority of B cells fail to exit G0. To determine whether cells in G1 are also susceptible to inhibition by BMC, we tested the ability of cells with NS activity to inhibit the LPS response of either low-density B cells or B cells preactivated by LPS. Both populations of cells were readily inhibited in their uptake of [3H]TdR. Direct analysis of B cell growth in suppressed cultures demonstrates that B cell numbers remain constant, with only 6-30% of the control number of B cells present in cultures containing BMC. Taken together, these results indicate that the antiproliferative effect of NS cells is a result of not only resting B cells being inhibited from entering the cell cycle, but also the inhibition of B cells already in G1.
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PMID:Effects of bone marrow-derived natural suppressor activity on B cell responses to lipopolysaccharide. 821 70

The origin of cells in almost all allogeneic donor-recipient pairs can be determined through the use of highly polymorphic minisatellite DNA probes. Single-locus probes were cloned from hypervariable fragments in a human DNA fingerprint detected with a multi-locus probe. While each probe is highly polymorphic and locus specific, they all contain repetitive sequences. The properties of single-locus probes have improved the sensitivity of detecting mixed chimerism in comparison with multi-locus probes. The use of single-locus probes permitted detection of mixed chimerism (MC) at levels as low as 0.625%, approaching that obtained by PCR methods. In the present study, five patients who received allogeneic BMT for hematologic malignancies were analyzed. Two patients exhibited MC after BMT. One developed acute GVHD and chronic GVHD and remained in CR while the second patient who had no signs of GVHD suffered a relapse.
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PMID:Evaluation of chimerism after bone marrow transplantation with single locus minisatellite DNA probes. 824 80

The follow-up of patients after bone marrow transplantation (BMT) revealed some discrepancies between red blood cell and white blood cell origin. In all six patients under study, the DNA analysis showed full engraftment, while red blood cells in some of them indicated persistence of recipient bone marrow activity. Abnormalities detected by the probe p362A (XY homologous region) in electrophoretic patterns observed during the period of graft versus host disease (GVHD) are discussed.
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PMID:Molecular follow-up of patients after bone marrow transplantation. 831 18


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