Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Administration of the adenosine analogue fludarabine (FLU) in vivo induces a profound and prolonged T lymphopenia which mainly affects CD4(+) cells. To better understand the mechanistic basis underlying this preferential depletion, we analyzed the in vitro susceptibility of T cell subsets to FLU-induced apoptosis. Contrasting with observations in vivo, our results showed that treatment of peripheral blood mononuclear cells with FLU induced a higher level of apoptosis in CD8(+) than in CD4(+) T lymphocytes. This increased sensitivity of CD8(+) T cells to FLU was observed in samples from both, healthy donors and B cell chronic lymphocytic leukemia patients, and resulted in higher CD4:CD8 ratios in FLU-treated than in untreated cultures (P<0.01). Expression of factors involved in FLU transport and metabolism was then evaluated by quantitative real time-PCR in normal T cell subsets. It was found that mRNA levels of human equilibrative nucleoside transporter-1 nucleoside transporter were higher whereas deoxycytidine kinase and IMP/GMP selective 5'-nucleotidase mRNA levels were lower in CD4(+) cells. However the dCK/cN-II ratio was 2-fold greater in CD8(+) than in CD4(+) T lymphocytes, which could account for the higher apoptosis levels observed in the CD8(+) subset. These results favor the view that decreased CD4:CD8 ratios in FLU-treated patients should be attributed to differences in cell recovery and/or homing between T cell subsets.
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PMID:In vitro susceptibility of CD4+ and CD8+ T cell subsets to fludarabine. 1460 43

Inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme for de novo synthesis of guanine nucleotides, is required for lymphocyte proliferation. Inhibition of IMPDH by mycophenolic acid (MPA) constitutes part of an immunosuppressive therapy in kidney allograft recipients. The 3757T>C polymorphic variant (rs11706052) of the IMPDH2 gene, which encodes 1 of 2 IMPDH isoenzymes, has been associated with increased IMPDH activity and reduced ability of MPA to exert antiproliferative effects on lymphocytes. The association of IMPDH2 3757T>C SNP with posttransplant courses of kidney allograft recipients remains unclear. Therefore, the aim of the present study was to evaluate associations between this single nucleotide polymorphism and common posttransplant complications among Polish kidney allotransplant recipients. We observed that the frequency of IMPDH2 3757C allele in this group (n=177) did not differ significantly from a control cohort representing the background population of Poland (n=550). There were no significant differences between patients carrying the IMPDH2 3757CT and TT genotypes with respect to acute rejection risk, neutropenia, or incidences of serious infections or gastrointestinal side effects. However, we noted that the 3757C allele was associated with higher lymphocyte counts and a reduced incidence of lymphopenia among kidney allograft recipients. Our findings may be of practical significance to tailor immunosuppressive regimens in kidney transplant recipients.
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PMID:Lymphocyte counts in kidney allograft recipients are associated with IMPDH2 3757T>C gene polymorphism. 2199 96