Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immune mechanisms have been shown to contribute to the process of myelodysplastic syndromes (MDS)-related bone marrow (BM) failure. The aim of this study was to evaluate the possible contribution of activated monocytes through CD40-CD40L(CD154) interactions with activated T helper cells. We demonstrated in 77 predominantly lower risk MDS patients that the CD40 receptor was expressed significantly higher on monocytes and that CD40L was expressed significantly higher on T helper cells in peripheral blood (PB) and BM. Increased levels of CD40 and CD40L were detected in the same patients. In addition, stimulation of the CD40 receptor on purified PB monocytes led to a significantly higher tumor necrosis factor alpha production in patients. Co-culture of BM mononuclear cells of 21 patients in the presence of a blocking CD40 monoclonal antibody (ch5D12) led to a significant increase in the number of colony-forming units. A correlation was seen between increased CD40 expression on monocytes with patients' age below 60 years and with the cytogenetic abnormality trisomy 8. These results demonstrate that CD40 expression on monocytes may identify a subgroup of MDS patients in whom immune-mediated hematopoietic failure is part of the disease process. As such, the CD40-CD40L-based activation of monocytes might be a target to counteract MDS-related BM failure.
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PMID:Monocytes are activated in patients with myelodysplastic syndromes and can contribute to bone marrow failure through CD40-CD40L interactions with T helper cells. 1780 23

The study was aimed to detect the expressions of costimulatory molecules on CD3(+)CD4(+) T cells so as to accumulate informations for investigation of mechanism of myelodysplastic syndrome. 11 healthy blood donors as control and 38 patients with MDS de novo were studied. 38 MDS patients were divided into RA/RARS group and RAEB/RAEB-t group according to FAB classification. The expressions of CD28, CD154, CTLA-4, PD-1, CD25 on CD3(+)CD4(+) T cells in peripheral blood were detected by FCM. The results indicated that as compared with normal controls, the expression of CD28 in MDS patients decreased, and CD154 increased. The percentages of CTLA-4, PD-1 and CD25 in MDS were obviously higher than that in normal controls; the differences of CTLA-4, PD-1 and the ratio of CTLA-4/CD28 between RAEB/RAEB-t and RA/RARS were more significant with progressing of MDS. In conclusion, the expressions of costimulatory molecule in MDS patients were abnormal, which may be involved in the pathogenesis of MDS.
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PMID:[Expressions of costimulatory molecules on CD3(+)CD4(+) T cells in myelodysplastic syndrome]. 1892

Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic diseases which have a high risk of progressing to acute myeloid leukemia. MDS patients have immunologic deficiency, including T and B cells dysfunction. Follicular T helper cells (Tfh, CD4+CXCR5+) are an important subset of helper T cells which help to the formation of germinal centers and B cells differentiation. In this study, we investigated the proportion and function of Tfh using NUP98-HOXD13 transgenic (NHD13) mice model with MDS phenotype. The proportion of Tfh from bone marrow and spleen of NHD13 mice decreased compared with wild type (WT) mice tested by flow cytometry. In NHD13 mice spleens, there were decreased CXCR5+ cells and increased PD-1+ cells using immunohistochemistry. The active markers (ICOS, CD40L and OX40) expressed on Tfh of NHD13 mice were decreased. In contrast, PD-1 expression on Tfh of NHD13 mice was higher than that of WT mice. After coculture with Tfh from NHD13 mice, IgG and IgM production of B cells were decreased. In conclusion, the proportion and function of Tfh in the MDS mice model were altered. The dysfunction and reduction of Tfh may inhibit B cells differentiation and antibody production. Abnormal Tfh might contribute to the immune tolerance promoting the progression of MDS.
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PMID:Altered follicular helper T cell impaired antibody production in a murine model of myelodysplastic syndromes. 2922 88