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Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by an isolated decrease in platelets below 100 × 109/l after the exclusion of other conditions associated with thrombocytopenia. We investigated the role of different memory T-cell subsets, including T stem cell memory (TSCM), in children diagnosed with primary ITP and its association with therapeutic duration. This case-control study included 39 pediatric patients with acute ITP admitted to the Children's Hospital at Assiut University. Using a FACSCanto flow cytometer, CD8 + and CD4 + T-lymphocytes were gated. Five different subsets were characterized in each of these cells according to CD45RO and CD45RA expression. Afterward, gating was performed based on CCR7, CD95, and CD27. Examination of the CD8 + T cells subpopulation showed that Central memory T (TCM) and CD8+ Naïve T (TN) cells were significantly lower in ITP patients than in healthy children (p < 0.0001) and (p = 0.01), respectively. In addition, CD8 + TEMRA was significantly higher in ITP children than in controls (p = 0.001). CD4 + TCM cells were significantly lower in the ITP patient group (p = 0.04). However, CD4 + TEM was significantly higher in patients than controls (p = 0.04). Our research found that ITP patients had an imbalance in the ratio of CD4+ to CD8+ T cells in the peripheral blood and that TCM cells may be involved in the pathogenetic mechanism of ITP. TCMs could help in prediction of patients with higher risk of developing ITP.
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Linfócitos T CD8-Positivos , Citometria de Fluxo , Células T de Memória , Púrpura Trombocitopênica Idiopática , Humanos , Criança , Púrpura Trombocitopênica Idiopática/imunologia , Feminino , Masculino , Estudos de Casos e Controles , Pré-Escolar , Linfócitos T CD8-Positivos/imunologia , Células T de Memória/imunologia , Linfócitos T CD4-Positivos/imunologia , Adolescente , Subpopulações de Linfócitos T/imunologia , Memória Imunológica , LactenteRESUMO
Background: Viral infections can cause direct and indirect damage to hematopoietic stem cells. The objectives of this study were to identify the frequency and severity of aplastic anemia in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as recognize the response to treatment. Methodology: 13 children with newly diagnosed severe aplastic anemia were enrolled in this prospective clinical trial. Blood samples were obtained from all patients to detect SARS-CoV-2 antibodies, and nasopharyngeal swabs were collected for reverse-transcription Polymerase Chain Reaction to detect SARS-CoV-2 viruses. According to the laboratory results, patients were classified as having SARS-CoV-2 positive antibodies and SARS-CoV-2 negative antibodies. Both groups received combined cyclosporine (CsA) + Eltrombopag (E-PAG). The hematological response, either complete response (CR) or partial response (PR), no response (NR), and overall response (OR) rates of combined E-PAG + CsA treatment after 6 months were evaluated. Results: Four children were recognized to have aplastic anemia and SARS-CoV-2 positive antibodies. Two patients fulfilled the hematological criteria for CR and no longer required transfusion of packed red blood cells (PRBCs) or platelets, and one had PR and was still PRBC transfusion-dependent but no longer required platelet transfusion. The remaining patient showed NR, and he had died before reaching the top of the HSCT waiting list. Moreover, six patients in the SARS-CoV-2 negative antibodies group had CR, while three patients had PR. The difference in ANC, Hg, and platelet counts between both groups was not significant. Conclusion: The SARS-CoV-2 virus is added to several viral infections known to be implicated in the pathogenesis of aplastic anemia. Studies are needed to establish a definitive association and determine whether the response of bone marrow failure to standard therapy differs from that of idiopathic cases.
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Background: Secondary iron overload, alloimmunization, and increased risk of infection are common complications in patients with transfusion-dependent thalassemia (TDT). Regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) play an essential role in preventing excessive immune response. This research aimed to study the interaction between Tregs and MDSCs in TDT patients and to evaluate the association of these cell types with disease severity. Methods: This case-control study included 26 patients with TDT and 23 healthy, age- and sex-matched controls. All patients were investigated for complete blood count (CBC), serum ferritin, and flow cytometric analysis of peripheral blood to detect Tregs, MDSCs, and MDSC subsets. Results: A significant increase was observed in the frequencies of Tregs and MDSCs, particularly monocytic MDSCs (MO-MDSCs), in TDT patients compared with controls. The frequencies of these cells showed a direct association with ferritin level and total leukocyte count and an inverse association with hemoglobin level. Furthermore, a positive correlation was observed between Tregs and each of the total MDSCs and MO-MDSCs. Conclusions: Levels of Tregs and MDSCs increased in TDT and may probably have a role in suppressing the active immune systems of TDT patients.
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BACKGROUND: Hydroxyurea (HU) has beneficial effects in the management of sickle cell anemia (SCA), but there is a paucity of data on the effect of HU on immune cells in SCA. Herein we aimed to evaluate the effect of HU on immune profiles of Egyptian children with SCA. METHODS: This was a controlled prospective cohort study conducted in 30 children with SCA and 30 healthy age-matched controls. Flow cytometry was used to evaluate lymphocyte profiles, including CD8+ T, CD19+ B, CD3+, CD4+, natural killer (NK), NK T, T helper 1 (Th1), Th2, T cytotoxic (Tc1), and Tc2 cells, prior to and after 1 year of treatment with HU. RESULTS: HU treatment led to significant increases in hemoglobin (Hb), red blood cell, and hematocrit counts and a significant decrease in the percentage of sickle Hb, with subsequent improvement in SCA complications. Compared with baseline values, CD3+, CD4+, Th1, and CD8+ T cells were significantly increased, while NK, Th2, and Tc2 cells were significantly decreased, with a resulting increase in the Th1/Th2 and Tc1/Tc2 ratios. CONCLUSIONS: HU has the beneficial effect of restoring the abnormally elevated immune parameters in children with SCA. IMPACT: Hydroxyurea treatment restores the abnormal immune parameters in children with sickle cell anemia. HU treatment led to significantly increased CD3+, CD4+, Th1, and CD8+ T cells, while NK, Th2, and Tc2 cells were significantly decreased, with a resulting increase in the Th1/Th2 and Tc1/Tc2 ratios. Our study showed the impact of HU therapy on immune parameters in children with SCA.
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Anemia Falciforme , Hidroxiureia , Humanos , Criança , Hidroxiureia/uso terapêutico , Células Th1 , Células Th2 , Estudos Prospectivos , Anemia Falciforme/tratamento farmacológico , Subpopulações de Linfócitos TRESUMO
Cytotoxic (CD8) T-cells and natural killer (NK) cells have a significant immune function role. The ongoing stimulation of immunity and the excessive release of proinflammatory cytokines observed in pediatric patients with Gaucher disease (GD) can affect immune cells. Few studies have looked at the proportion of cytotoxic CD8 T-cells and their subsets in children with GD. A prospective case-control study was performed involving twenty pediatric patients with type 1 GD and twenty healthy age-matched controls. All patients received regular enzyme replacement therapy (ERT) for at least 6 months before the study. Complete blood count and flow cytometric analyses of CD8 T, Tc1, Tc2, NK, and NK T-cells were performed. GD patients showed significantly increased of CD8 T, Tc1 and significantly decreased NK cells frequencies when compared to healthy controls. However, no significant difference in Tc2 and NK T-cells was found between the studied groups. GD patients on regular ERT have increased CD8+ T-cell frequencies, predominantly Tc1, together with a reduction in NK cells than in healthy controls. These crucial immunological changes may contribute to some extent to the pathogenesis and the progression of GD.
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Doença de Gaucher , Linfócitos T CD8-Positivos , Estudos de Casos e Controles , Criança , Humanos , Linfócitos T Citotóxicos , Regulação para CimaRESUMO
BACKGROUND: Regulatory T cells (Tregs) are linked to a reduction in alloreactive immune responses, but few studies have investigated the impact of hydroxyurea (HU) therapy on Tregs in sickle cell disease (SCD). METHODS: Our case-controlled study presented here included two groups, the first comprising 60 pediatric SCD patients, 30 of whom did not receive any treatment and 30 who received HU, and the second group consisting of 30 healthy controls. Flow cytometry was used to evaluate the percentage of CD4+CD25+highFoxp3+ Tregs present and their phenotypes. RESULTS: The percentage of CD4+CD25+high Tregs was significantly increased in untreated SCD patients in comparison to treated SCD patients and controls. Conversely, treated SCD children had a lower percentage of CD4+CD25+high Tregs than controls. In addition, a significant increase in the percentage of CD4+CD25+highFoxp3+ Tregs was found in untreated SCD patients, compared to in HU-treated patients and controls. The percentage of naive CD45RA+ Tregs was significantly decreased in untreated SCD patients when compared to other groups. CONCLUSIONS: Among children with SCD, HU treatment exhibited significant qualitative and quantitative effects on Tregs by decreasing their frequency, and increasing the proportion of naive CD45RA+ Tregs and reducing levels of the most suppressive Tregs: HLA-DR+, CD39+, and CD69+. IMPACT: Among children with, SCD, HU treatment exhibited significant qualitative and quantitative effects on Tregs. HU treatment in SCD decreases the frequency of Tregs, as well as the levels of the most suppressive Tregs: HLA-DR+, CD39+, and CD69+. At the same time, HU increases the proportion of naive CD45RA+ Tregs. Our study showed the impact of HU therapy on Tregs in children with SCD.
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Anemia Falciforme , Linfócitos T Reguladores , Anemia Falciforme/tratamento farmacológico , Criança , Fatores de Transcrição Forkhead , Antígenos HLA-DR , Humanos , FenótipoRESUMO
The Mediterranean hemopathic syndromes (MHS) are the most prevalent hemoglobinopathies in the Mediterranean basin. Transfusion therapy is the main therapy for these disorders, particularly for severe forms of the disease. Currently, pre-transfusion serological typing of erythrocyte antigens is the standard tool for reducing complications of transfusion in those patients. This study compared genotyping with phenotyping of non-ABO erythrocyte antigens in patients with MHS and assessed the effect of transfusion therapy on their results. One-hundred ninety-eight MHS patients were recruited, screened, and proven negative for allo-antibodies. They were grouped into two groups: (1) 20 newly diagnosed patients with no transfusion history and (2) 178 previously diagnosed patients undergoing transfusion therapy. Patients were interviewed and clinically examined. Full blood count (FBC) and high performance liquid chromatography (HPLC) were done for group 1 only. Genotyping and phenotyping of non-ABO erythrocyte antigens were performed for group 1, and 25 patients out of group 2 were propensity score-matched (PSM) with group 1. Both groups were gender and age matched; 55% and 74% of groups 1 and 2 had major disease, respectively. Insignificant differences were observed between genotyping and phenotyping of non-ABO erythrocyte antigens in group 1, while significant discrepancies and mixed field results were noted in group 2 patients. Discrepancies were obvious with JKa, JKb, and little c antigens. Conclusively, molecular typing is a powerful tool for pre-transfusion testing in chronically transfused MHS patients. This testing reduces incidence of transfusion reactions. JKa, JKb and little c antigens are the most clinically significant non-ABO erythrocyte antigens.
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Sistema ABO de Grupos Sanguíneos/imunologia , Genótipo , Hemoglobinopatias/imunologia , Fenótipo , Adulto , Humanos , MasculinoRESUMO
Our study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients' clinical and laboratory features, and the impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children's Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL.
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Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Células Supressoras Mieloides/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Adolescente , Fatores Etários , Biomarcadores , Estudos de Casos e Controles , Criança , Pré-Escolar , Suscetibilidade a Doenças , Feminino , Humanos , Imunofenotipagem , Lactente , Linfócitos do Interstício Tumoral/patologia , Masculino , Células Supressoras Mieloides/metabolismo , Células Supressoras Mieloides/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Prognóstico , Linfócitos T Reguladores/patologia , Microambiente TumoralRESUMO
BACKGROUND: There are minimal data on the frequencies of monocyte subsets and dendritic cells (DCs) in children with Gaucher disease (GD), as nearly all previous studies have involved adult patients. Consequently, we aimed to describe the changes in these cell subpopulations in children with GD type 1 who were on regular enzyme replacement therapy (ERT). METHODS: This case-control study included 25 children with GD1 and 20 healthy controls. All participants underwent investigations such as complete blood count and flow cytometric assessment of DC and monocyte frequencies and phenotype. RESULTS: We found that GD1 children had significantly reduced percentages of both types of DCs, i.e., plasmacytoid DCs and myeloid DCs, compared to the control group. There was also a significant reduction in absolute monocyte numbers and percentage of classical monocyte. Moreover, the GD1 children had higher frequencies of non-classical and intermediate monocytes than the control group. CONCLUSIONS: Our results so far indicate that, when compared to the control group, the GD1 children had significantly reduced total and classical monocyte, with significantly decreased frequencies for both types of DCs. These changes can contribute to immunological abnormalities in pediatric patients with GD1. IMPACT: Children with Gaucher disease type 1 (GD1) have significantly reduced total and classical monocyte frequencies, with decreasing percentages for both types of dendritic cells. GD1 children had significantly reduced frequencies of myeloid and plasmacytoid dendritic cells as compared to the controls. The GD1 children also had significant changes in monocyte subsets when compared to the controls. Our results show that monocytes and dendritic cells' significant changes could contribute to immunological abnormalities in pediatric patients with GD1.
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Células Dendríticas/citologia , Doença de Gaucher/imunologia , Monócitos/citologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Doença de Gaucher/patologia , Humanos , MasculinoRESUMO
Background: Dysfunction of the peripheral blood monocytes in the form of changes in their proportion, cytokines or pattern-recognition receptors (PRR) expressions may be involved in the pathogenesis of type 1 diabetes mellitus (T1DM). Our aim is to analyze the three monocyte subsets; classical, non-classical and intermediate monocytes and their expression of Toll-like receptors 2 (TLR-2) and 4 (TLR-4) in T1DM patients. Methods: The peripheral blood monocytes of 20 T1DM patients were analyzed by Flow cytometry to measure their count and TLR-2 and TLR-4 expression. Results: T1DM patients had more non-classical and intermediate monocytes, whereas classical monocytes were comparable between patients and control (20 healthy volunteers). Classical, non-classical and intermediate monocytes had no significant correlations with hemoglobin (Hb) A1C in controls, while all subsets showed positive correlations with HbA1C in T1DM. TLR-2 and TLR-4 expression were significantly increased in classical monocytes in patients, especially those with diabetic ketoacidosis (DKA), and both of them showed positive correlations with the duration of T1DM. The expression of TLR-2 inside non-classical monocytes showed a negative correlation with LDL cholesterol and TLR-4/TLR-2 ratio showed positive correlations with the duration of T1DM and negative correlations with total cholesterol. The expression of TLR-2 inside intermediate monocytes showed positive correlations with the duration of T1DM and TLR-4/TLR-2 ratio showed negative correlations with the duration of T1DM Conclusions: The observed changes in both proportions and TLR-2 and TLR-4 expression of monocyte subsets can raise the possible role in the pathogenesis of early stages of T1DM and DKA. Abbreviations APC: allophycocyanin; CBC: complete blood picture; DKA: diabetic acidosis; DM: diabetes mellitus; FITC: fluorescein isothiocyanate; FSC: forward scatter; Hb: haemoglobin; MFI: mean channel fluorescence intensity; PE: phycoerythrin; PRR: pattern-recognition receptors; SPSS: statistical package for the social sciences; SSC: side scatter; T1DM: Type1DM; TLRs: toll-like receptors.
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Diabetes Mellitus Tipo 1/imunologia , Cetoacidose Diabética/imunologia , Monócitos/fisiologia , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Separação Celular , Células Cultivadas , Criança , Pré-Escolar , Progressão da Doença , Feminino , Citometria de Fluxo , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genéticaRESUMO
This study intended to measure the expression of complement regulatory proteins CD55 and CD59 on RBCs membrane in patients with ß-thalassemia (ß- thal) major in addition to investigate if splenectomy affects their expression pattern. This was a case-control study, participants were allocated in three groups. The study group 1 consisted of ß-thal patients who underwent splenectomy. The study group 2 consisted of ß-thal patients without splenectomy. Group 3 consisted of apparently healthy volunteers as a control group. A significant decrease in CD55 expression in patients' group 1 (46.35±14.61) and group 2 (56.90±9.28) in comparison with group 3 (86.20±9.62) was observed. The percentage of CD55 expression was significantly lower in group 1 patients than group 2 (P=0.01). However, there was no difference in the percentage of CD59 marker expression between any of the patient's groups and the control group. In conclusion, CD55 under-expression on RBCs of ß- thal patients may be considered one of the factors that cause hemolysis in those patients and this complement mediated hemolysis may be one of the underlying causes of organ damage. Additional deficiency of this receptor occurs with splenectomy.
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Antígenos CD55/metabolismo , Antígenos CD59/metabolismo , Eritrócitos/metabolismo , Esplenectomia , Talassemia beta/sangue , Estudos de Casos e Controles , Hemólise , HumanosRESUMO
BACKGROUND AND AIM: There is a limited data at the moment regarding the clinical value of inflammatory indices and malnutrition markers in children with acute leukemias. We have examined the usefulness of prognostic nutritional index (PNI), Glasgow prognostic score (GPS), Prognostic Index (PI), monocyte to lymphocyte (MLR), neutrophil to lymphocyte (NLR), and platelet to lymphocyte (PLR) ratios to stratify patients as regards the response to induction therapy correlating them to different prognostic factors. PATIENTS AND METHODS: Children with acute leukemia and without microbial-induced inflammation at the time of diagnosis were prospectively recruited. Preliminary total and differential CBC, c-reactive protein (CRP), serum albumin (ALB) were used to calculate different inflammatory indicators including NLR, MLR, PLR, PNI, GPS, and PI. RESULTS: Higher PNI was significantly more associated to children who achieved remission as compared to those without remission (p< 0.0001). Patients without remission had GPS 1 or 2 compared to GPS 0 or 1 in those who entered remission (p= 0.001). NLR was significantly lower in patients in remission than in those without remission (p= 0.005). Similarly, complete remission was significantly associated to MLR ⩽ 0.45 as compared to MLR > 0.45 (p< 0.0001). CONCLUSION: Pretreatment PNI, GPS, CRP, serum albumin, NLR, MLR, and PLR are remission promising prognostic markers in pediatric acute leukemias, which deserve to be further investigated in large-scale studies.
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Leucemia/diagnóstico , Doença Aguda , Criança , Estudos de Coortes , Feminino , Humanos , Leucemia/patologia , Masculino , Prognóstico , Estudos ProspectivosRESUMO
Gaucher disease (GD) involves a broad spectrum of immunological cells, including T helper (Th) cells and regulatory B cells (Bregs), which function to resolve the immune response and inhibit excessive inflammation. This study aimed to explore T helper cells, B cells, and Bregs in GD children undergoing enzyme replacement therapy (ERT). Our study included 20 GD patients; six patients were categorized as type 1 and 14 as type 3 GD. All patients were on regular ERT. Twenty healthy children were enrolled as controls. All patients and controls were subjected to complete blood analysis, abdominal ultrasound, and flow cytometric detection of T helper cells, B cells, and Bregs. Despite undergoing ERT, CD4+ T helper lymphocytes and Bregs were still significantly lower in patients with GD compared with the controls. Th1 and B cells were more in the patients than in the healthy controls. Lower levels of Bregs were found in type 3, compared with type 1 patients. Increased platelet count was directly associated with increased levels of Bregs and lower levels of B cells. Elevated children's height was also accompanied by decreasing levels of Th1. Our results propose that ERT in GD is associated with partial improvement in immune status, and long-term ERT might be needed for the restoration of the desired immune response levels. Levels of Bregs and Th1 can be employed for monitoring improvement of immune status in GD patients undergoing ERT.
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Subpopulações de Linfócitos B/imunologia , Linfócitos B Reguladores/imunologia , Terapia de Reposição de Enzimas/métodos , Doença de Gaucher/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Células Th1/imunologia , Adolescente , Criança , Progressão da Doença , Egito , Feminino , Citometria de Fluxo , Doença de Gaucher/diagnóstico , Humanos , Imunofenotipagem , Masculino , Monitorização Imunológica , FenótipoRESUMO
Background and Aim. We studied through flow cytometry the expression of CD146 on different T cells, and B-cell ALL blasts trying to correlate its expression with different prognostic factors of B-cell ALL and treatment outcomes. Patients and Methods. All pediatric patients with B-cell ALL were subjected to bone marrow examination and cytochemistry, flow cytometric immunophenotyping using monoclonal antibodies utilized for diagnosis of B-ALL including CD34, CD19, CD10, CD22, and intracellular IgM. The diagnosis was based on standard morphologic, cytochemical, and immunophenotypic followed by flow cytometric detection of CD146 expression on blast cells, CD4+, and CD8+ T cells. RESULTS: Significant accumulations of CD146+CD4+ cells, CD146+CD8+ cells, CD4+, CD8+, and lymphocytes in patients were compared to controls, the mean percentages of CD146+CD4+ cells, CD146+CD8+ cells, and CD146+ blasts were significantly higher in patients than controls, and in addition, these cells were associated with poor overall survival and disease-free survival. The median OS for patients with complete response was 22 ± 1.633 (95%CI = 18.799-25.201), while for those without complete response, it was 13 ± 3.928 (95%CI = 5.301-25.699), with log-rank = 5.71, P = 0.017. CONCLUSION: CD146 was expressed significantly in children's B-ALL and associated with poor prognostic features including poor response and treatment outcomes and could be a possible poor prognostic factor in pediatric B-cell ALL.
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Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Antígeno CD146/genética , Antígeno CD146/metabolismo , Criança , Pré-Escolar , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Imunofenotipagem , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/etiologia , Prognóstico , Modelos de Riscos Proporcionais , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Resultado do TratamentoRESUMO
BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) was introduced as a potential inflammatory marker in sickle cell disease (SCD). This study aimed to evaluate the impact of hydroxyurea (HU) treatment on the value of NLR and some inflammatory mediators in SCD. METHODS: The hematological parameters and clinical events were analyzed in 35 children with SCD under HU treatment and followed up for 1 year and in 20 healthy controls. Enzyme-linked immunosorbent assay was performed for the evaluation of proinflammatory cytokines, including interleukin (IL) 6, IL-8, high-sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor α (TNF-α). RESULTS: Hydroxyurea significantly improves most of the hematological parameters in children with SCD. The percentages of hemoglobin fraction S, serum levels of TNF-α and IL-6 were significantly decreased when compared to baseline value but did not reach the value of the healthy control. The HU treatment led to a significant decrease in NLR compared to the baseline values and reached healthy control values. Neutrophil-to-lymphocyte ratio was positively correlated with hs-CRP, TNF-α, and IL-8 serum levels and negatively correlated with percentage of fetal hemoglobin and hematocrit values. The cutoff value of NLR to expect a response to HU among SCD was 3.0, with 76% specificity and 85% sensitivity (area under the curve: 0.85, P < .0001). In conclusion, hydroxyurea induced a decrease in NLR and inflammatory cytokines, which represent a biomarker of inflammation in SCD. The calculation of NLR is a straightforward and cheap method for SCD outcome prediction in young children.
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Anemia Falciforme/patologia , Hidroxiureia/farmacologia , Inflamação/diagnóstico , Linfócitos/citologia , Neutrófilos/citologia , Adolescente , Anemia Falciforme/tratamento farmacológico , Biomarcadores/sangue , Contagem de Células , Criança , Pré-Escolar , Citocinas/metabolismo , Feminino , Humanos , Hidroxiureia/uso terapêutico , Inflamação/tratamento farmacológico , Masculino , PrognósticoRESUMO
Gaucher disease (GD) is one of the most important lysosomal storage disorders. T-lymphocytes perform and regulate many of the immune processes and play a major role in immune homeostasis. Studies have shown that GD causes impairment in T-lymphocyte functions, although the role and status of T-lymphocytes in GD are still under investigation. It is still not fully known how GD leads to the altered biochemical and immunological cellular functions observed in the disease. Our study aimed to evaluate the variations of regulatory T-lymphocytes (Tregs) in 20 Egyptian children with GD under enzyme replacement therapy, managed in Assiut University Hospitals. Tregs were detected using 3-color flow cytometric immunophenotyping, in which subpopulations of T-lymphocytes and the expression of CD4+ on their surfaces were gated. The expression of CD25+ was assessed on CD4+ cells with different gates to define CD4+CD25, CD4+CD25+high, and CD4+CD25+ low cells. Then, CD4+CD25+highFoxp3+cells and MFI of Foxp3+ expression on CD4+CD25+ high were determined. We found the levels of CD4+CD25+/CD4+, CD4+CD25+high/CD4+, CD4+CD25+highFoxp3+ Tregs, and median fluorescence intensity of Foxp3+ expression on CD4+CD25+high were significantly lower in children with GD compared to healthy controls. In conclusion, our data showed significantly decreased regulatory T-lymphocytes in children with GD. The reduced effect of Tregs may have a role in the pathogenesis of immune dysregulation in children with GD. The relationship of these cells to immune disorders in GD children remains to be determined. Therefore, we recommend further studies to elucidate the role and function of Tregs in GD and its potential role in the disease phenotype, as well as how it is affected by electrical resistivity tomography.
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Terapia de Reposição de Enzimas/métodos , Doença de Gaucher/genética , Linfócitos T Reguladores/metabolismo , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Regulação para Baixo , Feminino , Doença de Gaucher/tratamento farmacológico , Humanos , MasculinoRESUMO
Juvenile idiopathic arthritis (JIA) is one of the most common autoimmune diseases in children. Our study aimed to evaluate the peripheral blood B and T lymphocyte subpopulations in children with JIA. This case-control study included 20 children with JIA as well as 20 healthy children with matching age and sex as a control group. All patients included in the study were in activity as determined by visual analog scale. In addition to complete clinical evaluation, basic investigations, peripheral blood B and T lymphocyte subpopulations were done to all participants by flow cytometry. JIA patients displayed a significant decrease in IgM memory B lymphocytes, switched memory B lymphocytes, and total memory B lymphocytes when compared to the healthy controls. The percentages of naïve B lymphocytes were significantly increased in JIA patients than in controls. Total T lymphocytes, CD8+CD28null cells, and CD4+CD28null cells were significantly increased in JIA patients as compared to controls. In conclusion; JIA patients have an alteration in both B and T lymphocytes with the predisposition of memory cells which may have a role in sustaining the JIA disease activity.
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Artrite Juvenil/imunologia , Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Subpopulações de Linfócitos/imunologia , Adolescente , Estudos de Casos e Controles , Criança , Progressão da Doença , Feminino , Citometria de Fluxo , Humanos , Imunoglobulina M/metabolismo , Memória Imunológica , Masculino , Escala Visual AnalógicaRESUMO
The contribution of innate immune cells, including natural killer (NK) and natural killer T (NKT) cells, in systemic lupus erythematosus (SLE) is still unclear. Herein, we examined the frequency of peripheral NK cells, CD56dim and CD56bright NK cells, and NKT cells in patients with juvenile SLE and their potential relations to SLE-related clinical and laboratory parameters. The study included 35 SLE children and 20 apparently healthy controls. After baseline clinical and lab work, SLE Disease Activity Index (SLEDAI-2K) and Pediatric Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (Ped-SDI) scores were assessed. The frequency of peripheral NK cells, CD56dim and CD56bright NK cells, and NKT cells was examined using flow cytometry. SLE patients showed significantly lower frequency of NK cells and NKT cells and higher frequency of CD56bright NK cells compared to controls. Disease activity, urea, and creatinine correlated negatively with NK, but positively with CD56bright NK cells. NK and NKT cells exhibited inverse correlation with the renal biopsy activity index; however, CD56bright NK cells showed direct correlations with both activity and chronicity indices. Regarding Ped-SDI, renal, neuropsychiatry disorders, and growth failure correlated inversely with NK but directly with CD56bright NK cells. NKT cell inversely correlated with renal damage and delayed puberty. In conclusion, low frequency of NK and NKT and expansion of CD56bright NK cells are marked in juvenile SLE, particularly with activity. These changes have direct effect on renal impairment and growth failure, reflecting their potential influence on disease progression.
Assuntos
Antígeno CD56/metabolismo , Células Matadoras Naturais/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Células T Matadoras Naturais/imunologia , Adolescente , Antígeno CD56/imunologia , Separação Celular/métodos , Criança , Estudos Transversais , Progressão da Doença , Feminino , Citometria de Fluxo/métodos , Humanos , Imunidade Inata , Células Matadoras Naturais/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/patologia , Masculino , Células T Matadoras Naturais/metabolismo , Índice de Gravidade de DoençaRESUMO
Sickle cell disease (SCD) is a genetically inherited hemolytic anemia increasingly appreciated as a chronic inflammatory condition and hypercoagulable state with high thrombotic risk. It is associated with disturbed immune phenotype and function and circulating microparticles (MPs) derived from multiple cell sources. This study was carried out to determine MPs profiles in patients with sickle cell anemia (either on hydroxyurea (HU) therapy or those with no disease-modifying therapy) and to compare these profiles with healthy children. Moreover, our study assesses the potential impact of HU on other aspects of circulating MPs. We performed a cross-sectional study on 30 pediatric patients with SCD divided by treatment into 2 groups (those receiving HU or no therapy) attending Hematology Clinic and 20 age-matched healthy children. The blood samples obtained were analyzed for MPs by flow cytometry. Sickle cell disease group with no therapy showed elevated levels of total, platelet, and erythroid MPs. In contrast, therapy with HU was associated with normalization of MPs. This study provided additional evidence that HU is an effective treatment option in pediatric patients with SCD, as it seems that it decreases the abnormally elevated MPs in those patients.
Assuntos
Anemia Falciforme/sangue , Micropartículas Derivadas de Células/metabolismo , Anemia Falciforme/metabolismo , Criança , Egito , Feminino , Citometria de Fluxo , Humanos , Masculino , Centros de Atenção TerciáriaRESUMO
BACKGROUND AND AIM:: Hyperglycemia in type 1 diabetes (T1D) is accompanied by endothelial cell dysfunction which is known to contribute to the pathogenesis of cardiovascular disorders. The aim of the current study was to explore the profile of circulating endothelial progenitor cells (EPCs), circulating endothelial cells (CECs), endothelial and platelet derived micropaticles (EMPs, PMPs) and total microparticles (TMPs), in T1D children in relation to each other and to the metabolic disorders accompanying T1D. PATIENTS AND METHODS:: Thirty T1D patients and 20 age and sex matched healthy volunteers were assessed for HbA1c level and lipid profile. Quantification of CECs, EPCs, TMPs, EMPs and PMPs was done by flow cytometry. RESULTS:: The mean levels of EMPs, PMPs, TMPs and CECs were significantly higher in diabetic children compared to controls. Meanwhile, the levels of EPCs were significantly lower in diabetic children compared to controls. Both PMPs and CECs showed the highest significant differences between patients and controls and their levels were directly related to HbA1c, total cholesterol, LDL and triglycerides. A moderate correlation was observed between the frequency of PMPs and CECs. EPCs revealed negative correlations with both LDL and triglycerides. TMPs were only related to LDL, while EMPs were only related to HbA1c. CONCLUSION:: Although there is disturbance in the levels of EMPs, PMPs, TMPs, CECs and EPCs in type 1 diabetic children compared to the controls, only the levels of PMPs and CECs were closely affected by the poor glycemic control and dyslipidemia occurring in T1D; thus may contribute to a higher risk of cardiovascular diseases.