Maria Ximeri

Publications (5)20.64 Total impact

• Source

  Available from: auth.gr

  Article: T-cell receptor Vβ repertoire analysis in patients with chronic idiopathic neutropenia demonstrates the presence of aberrant T-cell expansions.

  Michael Spanoudakis, Helen Koutala, Maria Ximeri, Katerina Pyrovolaki, Kostas Stamatopoulos, Helen A Papadaki
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  ABSTRACT: Chronic idiopathic neutropenia (CIN) is a bone marrow (BM) disorder characterized by presence of activated T-lymphocytes in peripheral blood (PB) and BM. We investigated the pattern of T-cell responses in CIN by analyzing the T-cell receptor β-chain variable (Vβ) gene repertoire. Compared to controls, CIN patients displayed different patterns of Vβ gene usage in PB CD3(+), CD4(+) and CD8(+) cells. The frequency of Vβ skewing and the number of expanded Vβ families per subject were higher in patients compared to controls in all cell subpopulations. Skewing was more profound within the CD8(+) cells. The number of Vβ expansions per patient was higher in BM compared to PB. The majority of patients displayed a skewed oligoclonal/monoclonal pattern within the PB and/or BM CD8(+) cells and a polyclonal profile within the CD4(+) cells. We concluded that aberrant T-cell expansions are invariably detected in CIN patients and may have a role in the disease pathogenesis.
  Clinical Immunology 12/2010; 137(3):384-95. · 4.05 Impact Factor
• Source

  Available from: Argiris Symeonidis

  Article: Effect of lenalidomide therapy on hematopoiesis of patients with myelodysplastic syndrome associated with chromosome 5q deletion.

  Maria Ximeri, Athanasios Galanopoulos, Mirjam Klaus, Agapi Parcharidou, Krinio Giannikou, Maria Psyllaki, Argyrios Symeonidis, Vasiliki Pappa, Zafiris Kartasis, Dimitra Liapi, Eleftheria Hatzimichael, Styliani Kokoris, Penelope Korkolopoulou, Constantina Sambani, Charalampos Pontikoglou, Helen A Papadaki
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  ABSTRACT: Lenalidomide improves erythropoiesis in patients with low/intermediate-1 risk myelodysplastic syndrome and interstitial deletion of the long arm of chromosome 5 [del(5q)]. The aim of this study was to explore the effect of lenalidomide treatment on the reserves and functional characteristics of bone marrow hematopoietic progenitor/precursor cells, bone marrow stromal cells and peripheral blood lymphocytes in patients with low/intermediate-1 risk myelodysplastic syndrome with del(5q). We evaluated the number and clonogenic potential of bone marrow erythroid/myeloid/megakaryocytic progenitor cells using clonogenic assays, the apoptotic characteristics and adhesion molecule expression of CD34(+) cells by flow cytometry, the hematopoiesis-supporting capacity of bone marrow stromal cells using long-term bone marrow cultures and the number and activation status of peripheral blood lymphocytes in ten patients with low/intermediate-1 risk myelodysplastic syndrome with del(5q) receiving lenalidomide. Compared to baseline, lenalidomide treatment significantly decreased the proportion of bone marrow CD34+ cells, increased the proportion of CD36(+)/GlycoA(+) and CD36(-)/GlycoA(+) erythroid cells and the percentage of apoptotic cells within these cell compartments. Treatment significantly improved the clonogenic potential of bone marrow erythroid, myeloid, megakaryocytic colony-forming cells and increased the proportion of CD34(+) cells expressing the adhesion molecules CD11a, CD49d, CD54, CXCR4 and the SLAM antigen CD48. The hematopoiesis-supporting capacity of bone marrow stroma improved significantly following treatment, as demonstrated by the number of colony-forming cells and the level of stromal-derived factor-1 alpha and intercellular adhesion molecule-1 in long-term bone marrow culture supernatants. Lenalidomide treatment also increased the proportion of activated peripheral blood T lymphocytes. The beneficial effect of lenalidomide in patients with lower risk myelodysplastic syndrome with del(5q) is associated with significant increases in the proportion of bone marrow erythroid precursor cells and in the frequency of clonogenic progenitor cells, a substantial improvement in the hematopoiesis-supporting potential of bone marrow stroma and significant alterations in the adhesion profile of bone marrow CD34(+) cells.
  Haematologica 09/2009; 95(3):406-14. · 6.42 Impact Factor
• Article: The -509C/T polymorphism of transforming growth factor-beta1 is associated with increased risk for development of chronic idiopathic neutropenia.

  Dimitrios G Eliopoulos, Irene Mavroudi, Charalampos Pontikoglou, Maria Ximeri, Emily Stavroulaki, Katerina Pyrovolaki, Maria Velegraki, Michael Spanoudakis, George Goulielmos, Helen A Papadaki
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  ABSTRACT: Impaired granulopoiesis in chronic idiopathic neutropenia (CIN) has been associated with an inflammatory bone marrow (BM) microenvironment consisting of pro-inflammatory and pro-apoptotic mediators, such as tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, and Fas-Ligand (Fas-L). In this study, we evaluated the frequency of TNF-alpha, TGF-beta1 and Fas-L gene polymorphisms in CIN patients and explored their role in excessive cytokine production and their association with CIN development. The TNF-alpha-308G/A, TGF-beta1 -509C/T, +869T/C, +915G/C, and Fas-L -844T/C polymorphisms were studied in 57 CIN patients, and 100 healthy controls from Crete, a well-defined area with genetically homogeneous population, using a polymerase chain reaction-based restriction fragment length polymorphism assay. The mutant genotype C/T or T/T of TGF-beta1 -509C/T polymorphism was more common in CIN patients than in controls (P = 0.033). Compared to wild-type genotype, the TT genotype was associated with increased risk for CIN development (OR: 5.7; 95% CI: 1.18-27.26; P = 0.033). Compared to controls, patients with CT and TT genotypes displayed increased TGF-beta1 levels in serum (P < 0.0001 and P = 0.0002, respectively) and BM (P < 0.0001 and P = 0.0002, respectively). No significant difference was found between patients and controls in the frequency of TNF-alpha-308G/A, TGF-beta1 +869T/C and +915G/C and Fas-L -844T/C polymorphisms. The TGF-beta1 -509C/T polymorphism is associated with increased risk for CIN and contributes to the pathophysiology of the disorder by inducing TGF-beta1 overproduction. This is the first study providing evidence that genetic factors may predispose to CIN and may have a role in the pathophysiology of the disorder.
  European Journal Of Haematology 07/2009; 83(6):535-40. · 2.61 Impact Factor
• Article: Transforming growth factor-beta1 affects interleukin-10 production in the bone marrow of patients with chronic idiopathic neutropenia.

  Katerina Pyrovolaki, Irene Mavroudi, Nicolas Papadantonakis, Maria Velegraki, Maria Ximeri, Christina Kalpadakis, Gilda Gvazava, Mirjam Klaus, George D Eliopoulos, Helen A Papadaki
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  ABSTRACT: Chronic idiopathic neutropenia (CIN) is a bone marrow (BM) failure syndrome characterized by accelerated apoptosis of myeloid progenitor cells because of a local imbalance between pro-inflammatory and anti-inflammatory cytokines. In this study, we investigated the interplay among transforming growth factor-beta1 (TGF-beta1), interleukin-10 (IL-10), and soluble flt-3 ligand (sFL) within the BM of CIN patients and probed the role of these cytokines in the pathophysiology of CIN. We used long-term BM cultures (LTBMC) to evaluate TGF-beta1, IL-10, and sFL levels in CIN patients (n = 70) and healthy subjects (n = 35). Cytokine levels in LTBMC supernatants were correlated with the number of circulating neutrophils and the proportion of BM CD34+/CD33+ myeloid progenitor cells. CIN patients had increased TGF-beta1 and sFL levels in LTBMCs compared with controls and individual cytokine values were found to be correlated inversely with the number of neutrophils and the proportion of CD34+/CD33+ cells. Patients displayed low supernatant IL-10 levels compared with controls and cytokine values were found to be correlated positively with the number of neutrophils and the proportion of CD34+/CD33+ cells. The levels of TGF-beta1 were found to be inversely correlated with IL-10 and positively with sFL values in LTBMC, supernatants suggesting a possible interplay among these cytokines in CIN BM. Neutralization of TGF-beta1 in LTBMCs increased IL-10 levels significantly in patients but not in controls, while neutralization had no effect on sFL levels. Excessive production of TGF-beta1 within the BM microenvironment of CIN patients results in downregulation of IL-10 and reduction of myeloid progenitor cells. Overexpression of sFL probably represents a compensatory mechanism to the low myeloid progenitor cells.
  European Journal Of Haematology 01/2008; 79(6):531-8. · 2.61 Impact Factor
• Article: Pro-inflammatory bone marrow milieu in patients with chronic idiopathic neutropenia is associated with impaired local production of interleukin-10.

  Vasiliki Koumaki, Athina Damianaki, Maria Ximeri, Charis Pontikoglou, Fani Axioti, Michael Spanoudakis, George D Eliopoulos, Helen A Papadaki
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  ABSTRACT: The levels of interleukin-10 (IL-10) were evaluated in long-term bone marrow (BM) culture supernatants from 54 patients with chronic idiopathic neutropenia (CIN) and 30 healthy volunteers using enzyme-linked immunoabsorbent assay. Cytokine levels were significantly reduced in patients, compared with controls, and strongly correlated with peripheral blood neutrophil counts. Low levels of supernatant IL-10 were associated with increased values of supernatant IL-1beta, tumour necrosis factor-alpha, IL-6 and transforming growth factor-beta(1). We suggest that the pro-inflammatory milieu in the BM of CIN patients may be causatively related to the impaired production of IL-10, a cytokine normally displaying strong anti-inflammatory properties.
  British Journal of Haematology 12/2006; 135(4):570-3. · 4.94 Impact Factor