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1.
Clin Immunol ; 253: 109691, 2023 08.
Article in English | MEDLINE | ID: mdl-37433423

ABSTRACT

In 15 Turkish LAD-1 patients and controls, we assessed the impact of pathogenic ITGB2 mutations on Th17/Treg differentiation and functions, and innate lymphoid cell (ILC) subsets. The percentage of peripheral blood Treg cells, in vitro-generated induced Tregs differentiated from naive CD4+ T cells were decreased despite the elevated absolute counts of CD4+ cells in LAD-1 patients. Serum IL-23 levels were elevated in LAD-1 patients. Post-curdlan stimulation, LAD-1 patient-derived PBMCs produced more IL-17A. Additionally, the percentages of CD18-deficient Th17 cells expanded from total or naïve CD4+ T cells were higher. The blood ILC3 subset was significantly elevated in LAD-1. Finally, LAD-1 PBMCs showed defects in trans-well migration and proliferation and were more resistant to apoptosis. Defects in de novo generation of Tregs from CD18-deficient naïve T cells and elevated Th17s, and ILC3s in LAD-1 patients' peripheral blood suggest a type 3-skewed immunity and may contribute to LAD-1-associated autoimmune symptoms.


Subject(s)
Leukocyte-Adhesion Deficiency Syndrome , T-Lymphocytes, Regulatory , Humans , Immunity, Innate , CD4-Positive T-Lymphocytes , Th17 Cells
2.
Infect Dis Clin Microbiol ; 5(1): 23-30, 2023 Mar.
Article in English | MEDLINE | ID: mdl-38633909

ABSTRACT

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 than asymptomatic patients (p<0.001 and p<0.001, respectively). We determined that decreased CD4+ T cell ratio (p<0.001) and CD4+ /CD8+ ratio (p<0.001) were indicative of the severity of the disease. CD4+ T cell ratio on admission (odds ratio [OR]=0.858; p=0.033), day seven CD4+ T cell ratio (OR=0.840; p=0.029), and C-reactive protein (CRP) levels (OR=1.014; p=0.043) were prognostic factors for mortality. According to receiver operating characteristics (ROC) curve analysis, the area under the curve was greater than 0.9 for decreased CD4 + T cell ratio on admission and the seventh day. Conclusion: A low CD4+ T helper ratio predicts a poor prognosis. In combination with CRP, it can be used in clinical follow-up.

3.
Med Hypotheses ; 144: 110202, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33254510

ABSTRACT

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.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , Imiquimod/therapeutic use , Toll-Like Receptor 7/agonists , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/therapeutic use , Antiviral Agents/administration & dosage , COVID-19/immunology , Humans , Imiquimod/administration & dosage , Immunity, Innate/drug effects , Models, Immunological , Pandemics , SARS-CoV-2 , Skin Cream
4.
Int Urol Nephrol ; 48(6): 891-9, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27068816

ABSTRACT

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Arteriovenous Shunt, Surgical , Endothelial Progenitor Cells/physiology , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/therapy , Monocytes/physiology , Renal Dialysis , AC133 Antigen/blood , Aged , Antigens, CD34/blood , Body Mass Index , Female , Humans , Male , Middle Aged , Prospective Studies , Vascular Endothelial Growth Factor Receptor-2/blood
5.
J Allergy Clin Immunol ; 132(5): 1156-1163.e5, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23910690

ABSTRACT

BACKGROUND: 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. OBJECTIVE: The aim of this study is to show the correlation between clinical, functional, and genetic data of patients with CGD from Turkey. METHODS: We report here the results of 89 patients with CGD from 73 Turkish families in a multicenter study. RESULTS: 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. CONCLUSION: 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.


Subject(s)
Granulomatous Disease, Chronic/diagnosis , Granulomatous Disease, Chronic/genetics , Cause of Death , Child, Preschool , Enzyme Activation , Female , Granulomatous Disease, Chronic/complications , Granulomatous Disease, Chronic/mortality , Humans , Incidence , Infections/etiology , Male , NADPH Oxidases/genetics , NADPH Oxidases/metabolism , Neutrophils/metabolism , Sequence Analysis, DNA
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