Toll-like receptor 7 is critical in recognition of single strand RNA viruses, including SARS CoV-... more Toll-like receptor 7 is critical in recognition of single strand RNA viruses, including SARS CoV-2, and generation of anti-viral immunity. Coronaviruses evolved strategies to dampen the host immunity. Herein, we discuss the potential use of TLR7 agonists in the early stages of COVID-19 treatment.
Objective: Most patients with coronavirus disease (COVID-19) have abnormalities of lymphocyte sub... more Objective: Most patients with coronavirus disease (COVID-19) have abnormalities of lymphocyte subsets. This study aimed to determine the distribution of lymphocytes in patients with various severity levels of COVID-19 and to describe the relationship between the CD4+ T helper and prognosis. Materials and Methods: Adult (>18 years old) patients with COVID-19 who followed up in a tertiary hospital were included in the study prospectively. Demographic and clinical characteristics of the patients were obtained from the hospital records. Peripheral flow cytometry was studied in patients with different severity of COVID-19 and different prognoses. Next, we analyzed the characteristics and predictive values of lymphocyte subsets in COVID-19 patients. Results: Totally 86 patients were included in the study, of which 21 (24.4%) had asymptomatic, 23 (26.7%) had mild/moderate, and 42 (48.8%) had severe/critical COVID-19. Severe/critical patients had lower lymphocyte levels and older age tha...
Abstract Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder characteri... more Abstract Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder characterized by impaired platelet aggregation due to defects in integrin αIIbβ3, a fibrinogen receptor. Platelet phenotypes and allelic variations in 28 Turkish GT patients are reported. Platelets αIIbβ3 expression was evaluated by flow cytometry. Sequence analyzes of ITGA2B and ITGB3 genes allowed identifying nine variants. Non-sense variation effect on αIIbβ3 expression was studied by using transfected cell lines. 3D molecular dynamics (MDs) simulations allowed characterizing structural alterations. Five new alleles were described. αIIb:p.Gly423Asp, p.Asp560Ala and p.Tyr784Cys substitutions impaired αIIbβ3 expression. The αIIb:p.Gly128Val substitution allowed normal expression; however, the corresponding NM_000419.3:c.476G>T variation would create a cryptic donor splicing site altering mRNA processing. The β3:p.Gly540Asp substitution allowed αIIbβ3 expression in HEK-293 cells but induced its constitutive activation likely by impairing αIIb and β3 legs interaction. The substitution alters the β3 I-EGF-3 domain flexibility as shown by MDs simulations. GT variations are mostly unique although the NM_000419.3:c.1752 + 2 T > C and NM_000212.2:c.1697 G > A variations identified in 4 and 8 families, respectively, might be a current cause of GT in Turkey. MD simulations suggested how some subtle structural variations in the β3 I-EGF domains might induce constitutive activation of αIIbβ3 without altering the global domain structure.
Arteriovenous fistula (AVF) failure is one of the most important clinical problems in end-stage r... more Arteriovenous fistula (AVF) failure is one of the most important clinical problems in end-stage renal disease. Endothelial progenitor cells (EPCs) have a role on vascular angiogenesis and endothelialization. We aimed to investigate the association markers of EPCs on AVF maturation by measuring the surface expressions of CD34, CD309 and CD133 on the monocytes. This prospective observational study was conducted in 54 voluntary patients with end-stage renal disease who were admitted for their first renal replacement therapy and were available for AVF creation. Venography was performed in all patients before AVF creation. Six patients were excluded due to inadequate veins after venographic imaging, and also seven patients were excluded due to postoperative thrombosis. The blood samples were analyzed a day before the fistula operation, and the expressions of CD34, CD133 and CD309 on the surface of monocytes were measured. Patients were divided into two groups after the evaluation of AVF maturation, as the mature group and the failure group. The CD309 expression level on the monocytes was 338.00 (35.00-479.00) in the mature group; however, it was 36.00 (5.50-237.00) (p 0.031) in the failure group. Multiple logistic regression analyses showed that both BMI and the mean fluorescence intensity level of CD309 expression on monocytes independently predicted AVF maturation. The presence of DM and increased BMI negatively correlated with AVF maturation. High intensity of CD309 expression on monocytes was observed in patients with successful AVF maturation.
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder of phagocytes res... more Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder of phagocytes resulting in impaired killing of bacteria and fungi. A mutation in one of the 4 genes encoding the components p22(phox), p47(phox), p67(phox), and p40(phox) of the leukocyte nicotinamide dinucleotide phosphate reduced (NADPH) oxidase leads to autosomal recessive (AR) CGD. A mutation in the CYBB gene encoding gp91(phox) leads to X-linked recessive CGD. The aim of this study is to show the correlation between clinical, functional, and genetic data of patients with CGD from Turkey. We report here the results of 89 patients with CGD from 73 Turkish families in a multicenter study. Most of the families (55%) have an AR genotype, and 38% have an X-linked genotype; patients from 5 families with a suspected AR genotype (7%) were not fully characterized. We compared patients with CGD according to the severity of NADPH oxidase deficiency of neutrophils. Patients with A22(0), A67(0) or X91(0) phenotypes with a stimulation index of 1.5 or less have early clinical presentation and younger age at diagnosis (mean, 3.2 years). However, in p47(phox)-deficient cases and in 5 other AR cases with high residual oxidase activity (stimulation index ≥ 3), later and less severe clinical presentation and older age at diagnosis (mean, 7.1 years) were found. Pulmonary involvement was the most common clinical feature, followed by lymphadenitis and abscesses. Later and less severe clinical presentation and older age at diagnosis are related to the residual NADPH oxidase activity of neutrophils and not to the mode of inheritance. CGD caused by A22(0) and A67(0) subtypes manifests as severe as the X91(0) subtype.
Toll-like receptor 7 is critical in recognition of single strand RNA viruses, including SARS CoV-... more Toll-like receptor 7 is critical in recognition of single strand RNA viruses, including SARS CoV-2, and generation of anti-viral immunity. Coronaviruses evolved strategies to dampen the host immunity. Herein, we discuss the potential use of TLR7 agonists in the early stages of COVID-19 treatment.
Toll-like receptor 7 is critical in recognition of single strand RNA viruses, including SARS CoV-... more Toll-like receptor 7 is critical in recognition of single strand RNA viruses, including SARS CoV-2, and generation of anti-viral immunity. Coronaviruses evolved strategies to dampen the host immunity. Herein, we discuss the potential use of TLR7 agonists in the early stages of COVID-19 treatment.
Objective: Most patients with coronavirus disease (COVID-19) have abnormalities of lymphocyte sub... more Objective: Most patients with coronavirus disease (COVID-19) have abnormalities of lymphocyte subsets. This study aimed to determine the distribution of lymphocytes in patients with various severity levels of COVID-19 and to describe the relationship between the CD4+ T helper and prognosis. Materials and Methods: Adult (>18 years old) patients with COVID-19 who followed up in a tertiary hospital were included in the study prospectively. Demographic and clinical characteristics of the patients were obtained from the hospital records. Peripheral flow cytometry was studied in patients with different severity of COVID-19 and different prognoses. Next, we analyzed the characteristics and predictive values of lymphocyte subsets in COVID-19 patients. Results: Totally 86 patients were included in the study, of which 21 (24.4%) had asymptomatic, 23 (26.7%) had mild/moderate, and 42 (48.8%) had severe/critical COVID-19. Severe/critical patients had lower lymphocyte levels and older age tha...
Abstract Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder characteri... more Abstract Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder characterized by impaired platelet aggregation due to defects in integrin αIIbβ3, a fibrinogen receptor. Platelet phenotypes and allelic variations in 28 Turkish GT patients are reported. Platelets αIIbβ3 expression was evaluated by flow cytometry. Sequence analyzes of ITGA2B and ITGB3 genes allowed identifying nine variants. Non-sense variation effect on αIIbβ3 expression was studied by using transfected cell lines. 3D molecular dynamics (MDs) simulations allowed characterizing structural alterations. Five new alleles were described. αIIb:p.Gly423Asp, p.Asp560Ala and p.Tyr784Cys substitutions impaired αIIbβ3 expression. The αIIb:p.Gly128Val substitution allowed normal expression; however, the corresponding NM_000419.3:c.476G>T variation would create a cryptic donor splicing site altering mRNA processing. The β3:p.Gly540Asp substitution allowed αIIbβ3 expression in HEK-293 cells but induced its constitutive activation likely by impairing αIIb and β3 legs interaction. The substitution alters the β3 I-EGF-3 domain flexibility as shown by MDs simulations. GT variations are mostly unique although the NM_000419.3:c.1752 + 2 T > C and NM_000212.2:c.1697 G > A variations identified in 4 and 8 families, respectively, might be a current cause of GT in Turkey. MD simulations suggested how some subtle structural variations in the β3 I-EGF domains might induce constitutive activation of αIIbβ3 without altering the global domain structure.
Arteriovenous fistula (AVF) failure is one of the most important clinical problems in end-stage r... more Arteriovenous fistula (AVF) failure is one of the most important clinical problems in end-stage renal disease. Endothelial progenitor cells (EPCs) have a role on vascular angiogenesis and endothelialization. We aimed to investigate the association markers of EPCs on AVF maturation by measuring the surface expressions of CD34, CD309 and CD133 on the monocytes. This prospective observational study was conducted in 54 voluntary patients with end-stage renal disease who were admitted for their first renal replacement therapy and were available for AVF creation. Venography was performed in all patients before AVF creation. Six patients were excluded due to inadequate veins after venographic imaging, and also seven patients were excluded due to postoperative thrombosis. The blood samples were analyzed a day before the fistula operation, and the expressions of CD34, CD133 and CD309 on the surface of monocytes were measured. Patients were divided into two groups after the evaluation of AVF maturation, as the mature group and the failure group. The CD309 expression level on the monocytes was 338.00 (35.00-479.00) in the mature group; however, it was 36.00 (5.50-237.00) (p 0.031) in the failure group. Multiple logistic regression analyses showed that both BMI and the mean fluorescence intensity level of CD309 expression on monocytes independently predicted AVF maturation. The presence of DM and increased BMI negatively correlated with AVF maturation. High intensity of CD309 expression on monocytes was observed in patients with successful AVF maturation.
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder of phagocytes res... more Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder of phagocytes resulting in impaired killing of bacteria and fungi. A mutation in one of the 4 genes encoding the components p22(phox), p47(phox), p67(phox), and p40(phox) of the leukocyte nicotinamide dinucleotide phosphate reduced (NADPH) oxidase leads to autosomal recessive (AR) CGD. A mutation in the CYBB gene encoding gp91(phox) leads to X-linked recessive CGD. The aim of this study is to show the correlation between clinical, functional, and genetic data of patients with CGD from Turkey. We report here the results of 89 patients with CGD from 73 Turkish families in a multicenter study. Most of the families (55%) have an AR genotype, and 38% have an X-linked genotype; patients from 5 families with a suspected AR genotype (7%) were not fully characterized. We compared patients with CGD according to the severity of NADPH oxidase deficiency of neutrophils. Patients with A22(0), A67(0) or X91(0) phenotypes with a stimulation index of 1.5 or less have early clinical presentation and younger age at diagnosis (mean, 3.2 years). However, in p47(phox)-deficient cases and in 5 other AR cases with high residual oxidase activity (stimulation index ≥ 3), later and less severe clinical presentation and older age at diagnosis (mean, 7.1 years) were found. Pulmonary involvement was the most common clinical feature, followed by lymphadenitis and abscesses. Later and less severe clinical presentation and older age at diagnosis are related to the residual NADPH oxidase activity of neutrophils and not to the mode of inheritance. CGD caused by A22(0) and A67(0) subtypes manifests as severe as the X91(0) subtype.
Toll-like receptor 7 is critical in recognition of single strand RNA viruses, including SARS CoV-... more Toll-like receptor 7 is critical in recognition of single strand RNA viruses, including SARS CoV-2, and generation of anti-viral immunity. Coronaviruses evolved strategies to dampen the host immunity. Herein, we discuss the potential use of TLR7 agonists in the early stages of COVID-19 treatment.
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