Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-1 receptor type 1 (IL-1R), IL-2 receptor alpha subunit (IL-2R) and IL-6 receptor alpha subunit (IL-6R) mRNA expression in peripheral blood mononuclear cells (PBMC) in 17 patients who underwent allogeneic bone marrow transplantation (allo BMT) and 2 patients who underwent autologous transplantation were analyzed using a semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). There were several exceptions in some cases and IL-1R expression was found to vary in a rather wide range, however, the expression of IL-2R and IL-6R mRNA tended to increase during the development of graft-versus-host disease (GVHD). In particular, IL-2R mRNA expression was increased in four patients with GVHD and graft failure. In contrast, IL-2R and IL-6R mRNA expression was not increased in autologous (auto) BMT and auto peripheral blood stem cell transplantation (PBSCT) patients. These findings suggest that IL-2R and maybe IL-6R mRNA expression in PBMC play an important role in the development of an allo response and GVHD. Therefore, the analysis of cytokine receptor mRNA expression in PBMC after allo BMT may provide important information concerning the immune response and the cytokine network system in marrow transplants.
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PMID:Cytokine receptor gene expression in peripheral blood mononuclear cells during graft-versus-host disease after allogeneic bone marrow transplantation. 853 20

Ex vivo IgG production was determined in 17 children and adolescents and in 14 adult patients between 10 months and 6 years after BMT. Twenty-four patients received allogeneic transplants. Seven patients were transplanted with autografts. Seven patients received immunosuppressive therapy. B cells were purified by positive selection with a CD20 antibody. After IL-2 or IL-10 stimulation, IgG production of SAC-preactivated B cells in patients with immunosuppression (median/range: 11/4-15 ng/ml or 14210-29 ng/ml) was significantly reduced compared with patients receiving allogenic (30/3-860 ng/ml or 33/2-3431 ng/ml; P < 0.01) or autologous transplants (75/7-1431 ng/ml or 269-/7-13600 ng/ml, P < 0.01). In 14/31 patients ex vivo IgG production was defective. Investigations of B cell function in patients with defective IgG production was performed significantly earlier after BMT compared with patients with normal IgG production ex vivo (2 +/- 1 years vs 3.3 +/- 1.5 years; P < 0.05). In addition, only patients with a B cell deficiency received immunosuppression. However, patients ex vivo IgG produced by B cells was decreased, but IgG production/sIgG+ B cells was within range of healthy volunteers. The number of IgG-committed B cells in these patients was significantly reduced compared to patients without deficiency (23/19-45/microliter vs 100/14-336/microliter; P < 0.05), indicating an in vivo switching defect. Although IL-10 is known to induce IgG-isotype switching in vitro, production of IL-10 by anti-CD3 activated MNCs obtained from patients with a switching defect did not differ from patients without B cell defects (1699/400-2662 pg/ml vs 724-112-1826 pg/ml). In nine patients IgG production and IgG production/sIgG+ B cells were impaired. The number of sIgG+ B cells was not decreased compared with patients without B cell deficiency (115/18-288/microliter), indicating a defective terminal differentiation of IgG-committed B cells to plasma cells. Although autocrine IL-6 is essential for plasma cell formation of isotype-determined B cells, it was comparable in patients with a terminal deficiency and without deficiency (3838/583-5967 pg/ml vs 2423/1643-6184 pg/ml). However, IL-10 production by anti-CD3 activated MNCs in patients with a terminal B cell defect (426/54-2262 pg/ml, P < 0.05) was significantly lower than in patients without deficiency, indicating a deviant cytokine production by T cells which might in part account for the B cell defect. Defective isotype switching as well as impaired terminal differentiation of B cells were found. Further analysis of factors regulating isotype-switching in vivo as well as cytokine receptor expression or signalling processes of differentiation factors in activated B cells might help to characterize the nature of these B cell deficiencies after BMT.
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PMID:Humoral immunodeficiency in patients after bone marrow transplantation. 897 82

The cytokine receptor common gamma chain (gamma c) plays a pivotal role in multiple interleukin signaling, and gamma c gene mutations cause an X-linked form of SCID (X-SCID). Recently, gamma c gene transfer into the autologous X-SCID BM achieved appreciable lymphocyte reconstitution, contrasting with the limited success in previous gene therapy trials targeting hematopoietic stem cells. To understand the mechanisms underlying this success, we examined the repopulating potential of the wild-type (WT) BM cells using an X-SCID mouse model. Limited numbers of WT cells were infused into non-ablated WT and X-SCID hosts. Whereas no appreciable engraftment was observed in WT recipients, donor-derived lymphocytes repopulated well in X-SCID, reaching 37% (10(6)cells given) and 53% (10(7) cells given) of the normal control value 5 months post BMT. A lineage analysis showed a predominance of the donor-derived lymphocytes (CD4(+) T, CD8(+) T, B and NK cells) in X-SCID while the donor-derived granulocytes and monocytes engrafted poorly. These results showed a selective advantage of WT cells in X-SCID, and that the advantage was restricted to lymphocytes. In human gene therapy for X-SCID, an analogous growth advantage would greatly enhance the repopulation of lymphocytes derived from a very small number of gamma c gene-supplemented precursors.
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PMID:Selective growth advantage of wild-type lymphocytes in X-linked SCID recipients. 1213 50