Browsing by Author "Dursun, Huseyin"

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Characterization of Peripheral Blood T Follicular Helper (Tfh) Cells in Patients With Type 1 Gaucher Disease and Carriers
(Academic Press inc Elsevier Science, 2023) Uzen, Ramazan; Bayram, Fahri; Dursun, Huseyin; Kardas, Fatih; Cakir, Mustafa; Cucer, Nurhan; Donmez-Altuntas, Hamiyet
Background: Gaucher disease (GD) is the most common autosomal recessive lipid storage disease. In this study, the changes in TFH cells and IL-4 and IL-21 cytokines in blood samples of GD patients, carriers and healthy volunteers were investigated.Methods: Two pretreatment type 1 GD patients, 20 currently treated type 1 GD patients, 6 carriers, and 27 healthy volunteers were enrolled in the study. TFH cell (CD45RA- CD4+CXCR5+) number, phenotype (PD1, ICOS expression), and cytokine production (IL-21, IL-4) were assessed via flow cytometric assays.Results: No significant differences were found between the groups with respect to the number, frequency and PD1 or ICOS expression of TFH cells between healthy controls, patients and carriers. However, IL-4+ TFH cells were significantly reduced both in percent and number in the treated GD patients compared with healthy controls (p < 0.05). Interestingly, the IL-21+ TFH cell number was increased in treated GD patients. When TFH cells were examined based on CXCR3 expression, the frequency of the PD1+Th17-Th2-like fraction (CXCR3-) was found to be significantly increased in treated GD patients. Conclusion: To our knowledge, this is the first study to assess TFH cells in GD patients, and to show that the production of IL-4 and IL-21 by TFH cells and their subsets may be altered in type 1 GD patients.
The Number and Frequency of Mucosal-Associated Invariant T (Mait), Γδ T, and Innate Lymphoid Cells (Ilcs) Altered in Patients With Type I Gaucher Disease
(Elsevier Science inc, 2025) Uzen, Ramazan; Bayram, Fahri; Dursun, Huseyin; Kardas, Fatih; Cakir, Mustafa; Cucer, Nurhan; Donmez-Altuntas, Hamiyet
Introduction: Gaucher disease (GD) is a rare lysosomal storage disease caused by mutations in the Glucocerebrosidase (GBA) gene. The innate immunopathology of GD beyond macrophage involvement is not well characterized. In the current study, the changes in ILC subsets, gamma delta T and MAIT cells, TNF-alpha and IFN-gamma cytokine levels in the peripheral blood of patients with Type 1 GD and GD carriers were evaluated. Methods: Peripheral blood mononuclear cells obtained from patients and controls were isolated using the Ficoll-Paque gradient method; after surface and intracellular staining, the cells were analyzed on FACSARIA III. Results: Our analyses revealed that CD8+ MAIT cells and CD8+ gamma delta T cells are reduced in the treated patients compared with the carriers. MAIT cell-specific IFN-gamma production and absolute counts of IFN-gamma+ MAIT cells significantly decreased in Type 1 GD patients who received ERT compared with healthy controls, which could be important indicators for the pathogenesis and severity of the disease. Additionally, total ILCs, particularly the ILC1 subset, were reduced in the Type I GD patients receiving ERT compared with healthy controls and the carriers. Conclusion: The changes observed in ILCs, gamma delta T cells, MAIT cells, TNF-alpha and IFN-gamma cytokine levels in both pre-and post-treatment Type 1 GD patients may play a vital role in the pathogenesis of GD.
Oxidative and Chromosomal Dna Damage in Patients With Type I Gaucher Disease and Carriers
(Pergamon-elsevier Science Ltd, 2023) Uzen, Ramazan; Bayram, Fahri; Dursun, Huseyin; Kardas, Fatih; Altin-Celik, Pinar; Cakir, Mustafa; Donmez-Altuntas, Hamiyet
Background and aims: Gaucher disease (GD) is caused by a genetic deficiency of the beta-glucocerebrosidase enzyme which results in the accumulation of glucosylceramide in macrophages. This accumulation may induce oxidative stress, resulting in DNA damage in patients with GD. The aim of this study was to assess plasma 8-hydroxy-2 '-deoxyguanosine (8-OHdG) levels and cytokinesis-block micronucleus cytome (CBMN-cyt) assay parameters in the peripheral blood lymphocytes of patients with GD and carriers, evaluate the possible associ-ations of these values with GD, and determine whether they can be used as potential biomarkers in GD.Methods: This study included 20 patients with type 1 GD, six carriers, and 27 age-and sex-matched healthy controls. CBMN-cyt assay parameters in peripheral blood lymphocytes of the patients with GD, carriers, and controls were evaluated and 8-OHdG levels in their plasma samples were measured.Results: CBMN-cyt assay parameters in patients with GD and carriers were not significantly different when compared with controls (p > 0.05). However, plasma 8-OHdG levels were found to be higher in both patients with GD and carriers than in control subjects (p < 0.01). Conclusions: Oxidative DNA damage may be a useful prognostic tool, whereas the CBMN-cyt assay cannot be used as a predictive biomarker of GD.
Tumor Suppressor and Oncogenic MiRNA Expressions in Patients With Type I Gaucher Disease and Carriers
(Bentham Science Publ Ltd, 2025) Uzen, Ramazan; Bayram, Fahri; Dursun, Huseyin; Kardas, Fatih; Cakir, Mustafa; Sohel, Md Mahmodul Hasan; Donmez-Altuntas, Hamiyet
Background: Gaucher disease (GD) occurs due to a mutation in the glucosylcerami-dase (GBA) gene and is a common lysosomal storage disease. It is well known that there is a strong association between the abnormal expression of miRNAs and various diseases including cancer. These abnormally expressed miRNAs can be used as biomarkers. Interestingly, several studies have reported a linkage between GD with an increased risk of cancer. Therefore, in the current study, we investigated the expression levels of selected miRNAs that are associated with cancers that might have potential use as biomarkers in GD. Methods: Blood samples were collected from 24 healthy volunteers, 6 carriers, and 20 treated patients with type 1 GD. A reverse transcription-quantitative real-time PCR (RT-qPCR) platform was used to analyze the miRNA expression levels. Results: While carriers had lower relative expressions of miRNA-15a with tumor suppressor ef-fect, and miRNA-150 and miRNA-181b with oncogene effect, treated patients with type 1 GD had lower relative expressions of miRNA-15a and miRNA-125b with tumor suppressor effect and higher relative expression miRNA-21 with oncogene effect (p<0.001, p<0.05, p<0.01, p<0.05, p<0.001, and p<0.05, respectively). Conclusion: The results suggested that the downregulation of miRNA-15a and miRNA-125b expressions with tumor suppressor effect and the upregulation of miRNA-21 expression with on-cogene effect can be indicated to an increased risk for cancers such as multiple myeloma (MM), B-cell lymphoma, leukemia, and hepatocellular carcinoma (HCC) in GD.