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)

MRL/l mice, which are homozygous at the lpr locus, can be inhibited in lpr phenotype expression (lymphadenopathy, accelerated death) by a transfer of MRL/n bone marrow cells following X-irradiation of the recipients (MRL/n bone marrow----X-irradiated MRL/l chimeras). Female MRL/l bone marrow----X-irradiated MRL/l chimeras express the lpr phenotype with a delay corresponding to the age at the time of cell transfer. However, the equivalent male chimeras resemble MRL/n bone marrow----X-irradiated MRL/l chimeras. When the reverse MRL/l bone marrow----X-irradiated MRL/n chimeras are constructed, one finds that whichever the sex is, the chimeras undergo a wasting disease looking like a graft-versus-host disease, with particularly a marked atrophy of the spleen. A similar GVH like disease is observed with C57Bl/6 lpr bone marrow----X-irradiated C57Bl/6 normal mice. These animals survive at least 5 months but manifest a spleen aplasia. When reconstituted with MRL/n bone marrow, MRL/l recipients develop higher levels of antinuclear and anti-ds/ss DNA antibodies than MRL/n recipients. This suggests that the 'lpr environment' of the host may have an influence on the development of B cell hyperactivity.
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PMID:Bone marrow transfers in X-irradiated mice congenic at the lpr locus: some paradoxical effects. 331 28

The sera of 26 patients with graft versus host disease (GVHD) were analyzed for the presence of autoantibodies. Because the clinical spectrum of GVHD resembles some of the systemic collagen vascular diseases, particular attention was given to antinuclear antibodies and autoantibodies directed against saline soluble cellular antigens. 39% (10/26) of the patients had a positive ANA at a titer of greater than or equal to 1/80. Antibodies to double-stranded DNA were demonstrated in 4 sera (15%), to smooth muscle in 9 (41%) and to nucleoli in 6 (22%). Three sera had precipitating antibodies to saline extracts of rabbit thymus and/or bovine spleen. None of these precipitins showed lines of identity with known autoantibody systems. High titers of ANA were correlated with a previous diagnosis of acute lymphoblastic leukemia and multiple autoantibodies correlated with the severity of GVHD.
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PMID:Autoantibody analysis of patients with graft versus host disease. 331 59

Twenty-two patients (acute myeloid leukaemia 13, acute lymphoid leukaemia 5, chronic myeloid leukaemia 4) with an average age of 25 years (range 8-36 years), had received allogeneic bone marrow transplantation (BMT) from an HLA identical sibling. The BMT recipients were followed up for a period of 4-65 months. All patients were given cyclophosphamide, total body irradiation and methotrexate in order to prevent graft-versus-host disease (GvHD). Eleven of 22 patients exhibited chronic graft versus host disease (cGvHD) (extensive in five, limited in six at the time of the study) assessed by clinical and histological parameters. Serum samples were collected from these patients, before BMT (except in one case) and then every 2 or 3 months. Sequential studies to determine the presence of autoantibodies against cytoskeletal proteins (actin, tubulin, myosin), dsDNA and dDNA in these sera were performed by an ELISA method. Simultaneously, immunoelectrophoresis and measurement of complement fractions C3, C4 were performed on each sample. High levels of autoantibodies against cytoskeletal proteins were found in 10/11 patients with cGvHD and were absent in 11/11 patients without cGvHD; none of them exhibited anti-DNA activity. At the same time, C4 levels were decreased in seven of these patients with cGvHD. Monoclonal immunoglobulins IgG and IgM (2-15 g/l) were found in 8/11, but the antibody activity was never found to be located within the M component. These results show a direct relationship between the presence of these autoantibodies and occurrence of cGvHD and indicate that they may constitute an immunological marker related to this complication. However, their predictive value is not clearly evident in this retrospective series as in some patients they preceded clinical signs of cGvHD, whereas in others they were associated with the onset of cGvHD.
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PMID:High levels of anti-cytoskeleton autoantibodies are frequently associated with chronic GVHD. 331 12

Mice bearing the 'auto-immune' lpr gene develop a lympho-proliferative disease associated with the production of various antibodies. Lethally irradiated recipients were grafted with bone marrow cells (BMC) from syngeneic mice with or without the lpr gene. After 6 months, the survivors were 0/24 and 16/20 for the recipients of lpr and normal BMC respectively. The mortality rate was independent of the presence of T lymphocytes among the BMC. Histological evaluation showed that hepatitis, interstitial pneumonitis, and sclerosis of lymphohaemopoietic organs were the major causes of death for the recipients of lpr BMC. Hepatitis was associated with an increase in the number of liver interstitial cells (LIC) from about 2 X 10(6) up to about 10(7) cells per liver. The LIC associated with the hepatitis were composed of polymorphonuclear leucocytes and large mononuclear leucocytes, showing phenotypic (i.e. Thy.1+, asialo GM1, presence of cytoplasmic granules) and functional (i.e. non-phagocytic and cytolytic) properties of NK cells. The disease can be distinguished both from the spontaneous disease of the lpr mice (by the absence of 'lpr cells' and of anti-DNA antibodies) and from graft versus host disease by the absence of cutaneous and intestinal lesions. It may represent a model of tissue injury mediated by large granular leucocytes.
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PMID:Interstitial pneumonitis and hepatitis after transfer of bone marrow cells bearing the lpr gene to irradiated recipients: a disease due to large granular leucocytes? 332 8

A quantitative analysis of the frequencies of autoantibody-producing B cells in GVHD and in normal mice has been undertaken by generating collections of hybridomas of activated B cells. These hybridomas secreted sufficient quantities of Ig to allow binding analyses on a panel of autoantigens. B cells have been activated in a variety of ways. In vivo they were activated by injection of alloreactive T cells of one parent, leading to GVHD by a foreign antigen, sheep erythrocytes, in a secondary response, or by the polyclonal activator LPS. B cells from an experimentally unstimulated animal were used for an analysis of the normal background. In vitro B cells were activated by alloreactive T cells or by LPS. The frequencies of hybridomas and, therefore, of activated B cells producing autoantibodies to DNA or to kidney were not significantly different in mice activated by a graft-vs.-host T cell response as compared with B cell populations activated by any of the other procedures. They were found to compose 7.1-17.1% of the total repertoire of activated B cells. Moreover, the frequencies of autoantibody-producing activated B cells does not change with time after induction of the graft-vs.-host reaction. The pattern and frequencies of autoantigen-binding specificities to cytoskeleton, smooth muscle, nuclei, mitochondria, and DNA were not found to be different in any of the groups of hybridomas. The single notable exception, found in GVHD mice, were hybridomas producing autoantibodies to kidney proximal tubular brush border. These results allow the conclusion that autoantigen-binding B cells exist in an activated state in GVHD mice, as well as in mice activated by a foreign antigen or by a polyclonal activator, in B cell populations activated in vitro either by alloreactive T cells or by a polyclonal activator, and even in the background of experimentally unstimulated animals. T cell-mediated graft-vs.-host activation, in large part, does not lead to a selective expansion of autoantigen-binding B cells. The main difference between the graft-vs.-host-activated B cell repertoire and all others is that approximately 90% of teh autoantibodies were of the IgG class, whereas al autoantibodies found in the other groups were IgM.
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PMID:The autoantigen-binding B cell repertoires of normal and of chronically graft-versus-host-diseased mice. 349 30

Systemic lupus erythematosus-like graft-versus-host (GVH) disease was induced in 10-week-old male (C57BL/10 X DBA/2) F1 mice by the intravenous injection of spleen and thymus cells (2:1) from 10-week-old male DBA/2 mice. GVH mice were bled at regular intervals 1 month after injection. Antibody to nuclear antigens (ANA) were detected by immunofluorescence using HEp-2 cells as substrate, and antibody to histones and DNA were detected by enzyme-linked immunosorbent assay (ELISA). The titer and frequency of ANA were found to relate directly to the number of donor cells injected. In order to determine the spectrum of ANA in GVH disease, mice were reinjected with optimum cell numbers (120 X 10(6], and splenocytes from two mice with high titer ANA were fused to mouse myeloma cell line P3/X63Ag8.653. Hybridomas were analyzed for ANA by immunofluorescence and ELISA. Sixty-eight clones were found which secreted ANA. Of these, 59% produced antibody to double-stranded DNA, single-stranded DNA, and/or histones and the remainder gave a variety of nuclear immunofluorescence patterns including speckled, homogeneous, nuclear matrix, and nucleolar. This study indicates that GVH disease provides an excellent source of splenocytes for the production of ANA-producing hybridomas as well as a model for the study of autoimmunity.
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PMID:Monoclonal autoantibodies to nuclear antigens from murine graft-versus-host disease. 349 80

(C57BL/6 X DBA/2)F1 mice undergoing the graft-vs-host reaction (GVHR) produce autoantibodies after the injection of DBA/2 lymphoid cells. The anti-nuclear antibodies, including anti-poly (ADP-ribose) and anti-extractable nuclear antigens (ENA), in the sera of the autoimmune GVH F1 mice were investigated. Antibodies to double-stranded DNA, single-stranded DNA and ENA were predominantly IgG. In contrast, the autoantibodies to poly(ADP-ribose) were both IgG and IgM, although the former was predominant. These autoantibodies induced by the GVHR showed similar cross-reactivities with a number of nucleic acids to the monoclonal and some serum antinuclear antibodies derived from mice or humans with systemic lupus erythematosus (SLE). These results support the idea that GVH F1 mice are a good model of human SLE.
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PMID:Specificity of anti-nuclear antibodies induced in F1 mice undergoing the graft-vs-host reaction: isotypes and cross-reactivities. 349 93

Highly purified populations of C57BL/6 (B6) L3T4+ and Lyt-2+ T cell subsets were compared for their capacity to exert alloreactivity to class I vs. class II H-2 differences in vivo. B6 Lyt-2+ cells responded strongly to the class I different mutant, bm1, as manifested by DNA synthesis in the spleen of irradiated mice followed by entry of blast cells into thoracic duct lymph, induction of splenomegaly in newborn mice, production of lethal GVHD in irradiated mice, and skin allograft rejection. By all of these parameters, B6 Lyt-2+ cells showed almost total unresponsiveness to the class II-different mutant, bm12. Reciprocal results were observed with B6 L3T4+ cells, these cells responding strongly against bm12 but not against bm1. In the case of purified T cell subsets from other strains, CBA/Ca and B10.BR L3T4+ cells both responded well to a full H-2 difference. Responses by Lyt-2+ cells from these strains were weaker, especially for CBA/Ca cells. The implications of these findings are discussed.
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PMID:Properties of purified T cell subsets. II. In vivo responses to class I vs. class II H-2 differences. 351 63

A lupus-like disease characterized by a severe immune complex glomerulonephritis and IgG autoantibody production was induced in (C57BL/6 X DBA/2)F1 mice by injection of parental DBA/2 lymphoid cells. The ensuing graft-vs-host (GVH) reaction resulted in a 10- and a 100-fold increase in serum IgG antibody levels to denatured DNA and total histones, respectively, compared with that in F1----F1 control mice. The level of anti-DNA antibodies peaked 2 wk after injection of DBA/2 cells and preceded peak anti-histone levels by approximately 2 wk. Anti-histone antibodies were generated predominantly to histones H1, H2A, and H2B, a profile different from that observed in NZB/NZW and MRL-lpr/lpr mice. The marked increase in IgG antinuclear antibodies did not correlate with increases in total IgG serum levels and was not associated with comparable increases in antibodies to transferrin, hemoglobin, fibrinogen, or thyroglobulin. Selective autoantibody production was also observed in vitro, wherein GVH spleen cells produced high levels of IgG antibodies to total histones and denatured DNA but not to these non-nuclear protein antigens. In contrast, spleen cells stimulated in vitro with lipopolysaccharide produced equivalent amounts of antibodies to all antigens tested. Our results are in agreement with those of other investigators and collectively suggest that IgG autoantibodies in GVH disease, and possibly in spontaneous lupus-like disease, are not secondary to a generalized B cell activation, but may be selectively generated in response to self antigens with unique configurational properties.
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PMID:Autoimmunization in murine graft-vs-host disease. I. Selective production of antibodies to histones and DNA. 387 58

In our model of GVHR, irradiated (DBA/2 X B10.D2)F1 mice were given splenic and bone marrow cells from B10.D2 donor mice. At different set times after the graft, recipient mice were given a single injection of a radioactive precursor of DNA (125IUdR) and killed one hour later. The radioactivity in excised organs reflected the label incorporation by the proliferating cells. When mice were killed from 1 hour to 96 hours after the label injection the residual radioactivity in individual organs reflected the number of the residual living cells arising from cells which were in S-phase during the label pulse. This study allowed us to specify the dynamics of the cell proliferative activity and the behavior of these proliferating cells through the whole organism at any time of a GVH disease. A very interesting point is that the minor non-H-2 histocompatibility antigens (MiHA) responsible of the GVHR induced a very important and specific stimulation of the grafted cell proliferation in all the non-lymphoid organs with a spatial and timing evolution through the whole organism. A great part of the cells specifically stimulated to divide by the MiHA are very short-lived. The remaining living cells migrate out of the spleen and bone marrow and accumulate into the non-lymphoid organs after a latency period lasting 12-24 hours following the label uptake. This cell invasion was mainly into the liver, vesicular glands, kidneys, salivary glands and lungs.
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PMID:Proliferation and migration of grafted hemopoietic cells during a graft-versus-host reaction induced by minor non-H-2 histocompatibility antigens in the mouse. 391 Jan 29


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