Mohamed Attia

HLA-G Expression as a Prognostic Indicator in B-Cell Chronic Lymphocytic Leukemia

Background: The expression of human leukocyte antigen (HLA)-G was studied in certain malignancies and its role in escaping from immunosurveillance in cancers was proposed since HLA-G is a non-conventional HLA class I molecule that protects the fetus from immunorecognition during pregnancy. Some particles involved in the regulation of an immune system might represent prognostic value for B-cell chronic lymphocytic leukemia (B-CLL). The identification of novel prognostic factors in B-CLL may help define patient subgroups that may benefit from early therapeutic intervention. Objective: To evaluate the prognostic significance of HLA-G expression in B-CLL patients and its relationship with other well-established prognostic markers. Methodology: Thirty B-CLL patients diagnosed by clinical, morphological and immunophenotyping criteria were studied for HLA-G expression by flow cytometry. The relationship between HLA-G expression and some known prognostic markers was evaluated. Results: HLA-G was expressed in 36.7% of CLL patients at diagnosis, with a mean expression level of 35.31 ± 12.35%. A significant association between HLA-G expression and common prognostic markers of progressive disease was detected. The group of patients with positive HLA-G expression showed significantly higher absolute lymphocyte counts and serum levels of LDH and β2-microglobulin, lower platelet counts, positive CD38 expression and advanced stages of Binet clinical staging. Conclusion: The present study demonstrated that HLA-G expression correlates with prognostic markers of a poor B-CLL outcome, mainly Binet clinical staging and CD38 expression by B-CLL cells, which indicates that this parameter may play a role as an important prognosticator of disease progression and consequently targeted therapy in B-CLL.

Effect of iron deficiency anemia and its treatment on cell mediated immunity

Iron deficiency anemia (IDA) is one of the most prevalent micronutrient deficiencies particularly in the developing countries. While there is evidence of an altered immune profile in iron deficiency, the exact immunoregulatory role of iron is not known. Knowledge particularly in children, who are vulnerable to iron deficiency and infection, is lacking. We aimed to study the effects of IDA and its treatment with oral iron supplementation on cell-mediated immunity. The levels of T-lymphocytes, their CD4+, CD8+ and CD1a+ subsets, transferrin receptor (CD71) and serum ferritin were evaluated in 40 iron-deficient and 40 healthy children. The impact of oral iron supplementation for three months on the same parameters was also noted in children with IDA. The level of mature T-lymphocytes (CD4+ and CD8+) was significantly lower (P<0.001) while that of the immature T-cells (CD1a+) was significantly higher (p<0.001) in IDA children compared to the control. The mature T-cell count was significantly improved after iron therapy. In spite of significant reduction in the immature T-cells (CD1a+) level after iron supplementation, it was significantly higher than the control. The present study demonstrated that T-lymphocytes maturation was defective in IDA and improved partially after 3 months of iron supplementation. Therefore, longer time of iron therapy may be required to induce complete maturation of T-lymphocytes.

Decreased Circulating T Regulatory Cells in Egyptian Patients with Nonsegmental Vitiligo: Correlation with Disease Activity.

Background. Vitiligo is an acquired depigmentary skin disorder resulting from autoimmune destruction of melanocytes. Regulatory T cells (Tregs), specifically CD4+CD25+ and Forkhead box P3+ (FoxP3+) Tregs, acquired notable attention because of their role in a variety of autoimmune pathologies. Dysregulation of Tregs may be one of the factors that can break tolerance to melanocyte self-antigens and contribute to vitiligo pathogenesis. Methods. In order to sustain the role of Tregs in pathogenesis and disease activity of vitiligo, surface markers for CD4+CD25+ and FoxP3+ peripheral Tregs were evaluated by flow cytometry in 80 Egyptian patients with nonsegmental vitiligo in addition to 60 healthy control subjects and correlated with clinical findings. Results. Vitiligo patients had significantly decreased numbers of both peripheral CD4+CD25+ and FoxP3+ T cells compared to control subjects (11.49%  ± 8.58% of CD4+ T cells versus 21.20%  ± 3.08%, and 1.09%  ± 0.96% versus 1.44%  ± 0.24%, resp., P < 0.05 for both). Peripheral numbers of CD4+CD25+ and FoxP3+ Tregs correlated negatively with VIDA score. Conclusion. Treg depletion with impaired immune downregulatory function might play a key role in the autoimmune conditions beyond nonsegmental vitiligo particularly in active cases. Effective Treg cell-based immunotherapies might be a future hope for patients with progressive vitiligo.

A proposed generalized mean single multiplicative neuron model

This paper presents a single multiplicative neuron model based on a polynomial architecture. The proposed neuron model consists of a non-linear aggregation function based on the concept of generalized mean of all multiplicative inputs. This neuron model has the same number of parameters as the single multiplicative neuron model (SMN). The SMN model is a special case of the proposed generalized mean single multiplicative neuron (GMSMN) model. The structure of this model is simpler than higher-order neuron model. The simulation results show that the performance of the proposed neuron model is better than SMN model.

Are Peripheral Natural Killer Cells and Interleukin-21 Interrelated in Psoriasis Pathogenesis?

108 Ann Dermatol Received August 10, 2015, Revised December 3, 2015, Accepted for publication January 5, 2016 Corresponding author: Doaa Salah Hegab, Department of Dermatology and Venereology, Faculty of Medicine, Tanta University Hospitals, El Geish Street, Tanta 31111, Al Gharbiyah governorate, Egypt. Tel: 20-1224500857, Fax: 20-403286114, E-mail: doaasalahhegab@yahoo.com This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/ licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright

Frequencies of circulating myeloid derived suppressor cells and dendritic cells in Egyptian patients with chronic Hepatitis C Virus infection undergoing treatment with IFN-α-based therapy

Background Hepatitis C Virus (HCV) is epidemic in Egypt and causes chronic hepatitis. Anti-HCVtherapy (IFN-a and Ribavirin) is only effective in 60% of patients with chronic HCV infection. This failure which is often associates with suppression of immunity results in progression of the disease and the development of hepatocellular carcinoma. Recent studies including ours have shown a positive correlation between accumulation of myeloid derived suppressor cells (MDSCs) and suppressed immunity in cancer and other diseases. Aim To assess the frequency of myeloid cells, including MDCS and dendritic cells (DCs) in chronic HCV patients and correlate it with the responses of the patients to IFNa-bases therapy. Methods

Single multiplicative neuron model based on generalized mean

This paper presents a single multiplicative neuron model based on a polynomial architecture. The proposed neuron model consists of a non-linear aggregation function based on the concept of generalized mean of all multiplicative inputs. This neuron model has the same number of parameters as the single multiplicative neuron model (SMN). The SMN model is a special case of the proposed generalized mean single multiplicative neuron (GMSMN) model. The structure of this model is simpler than higher-order neuron model. The simulation results show that the performance of the proposed neuron model is better than SMN model.

IFN-α-based treatment of patients with chronic HCV show increased levels of cells with myeloid-derived suppressor cell phenotype and of IDO and NOS

Abstract Introduction: Hepatitis C virus (HCV) infection causes chronic hepatitis, which is often associated with suppressed anti-HCV immune responses. We have recently reported accumulation of myeloid-derived suppressor cells (MDSCs) and suppressed immunity in cancer patients. Aim: The main aim of this study was to determine whether chronic HCV patients harbor high of MDSCs in general and in nonresponders to IFN-based therapy in particular as well as to analyze the immune suppressive molecules. Methods: Peripheral blood samples withdrawn from 154 patients with chronic HCV infection and were categorized into responders and nonresponders based on viral titer upon IFN-α treatment. Results: The relative and absolute numbers of MDSCs defined as Lin−/HLA-DR−/CD33+/CD11b+ increased in all HCV patients, where they were higher in nonresponders than in responders. Additionally, the levels of MDSCs after 4–6 months of treatment in responders were lower than during the course of treatment. The responders also showed higher levels of IL-2 coincided with increased numbers of dendritic cells (DCs), CD4+ and CD8+ T cells. The levels of total NOS and IDO were also higher in nonresponders as compared to responders and healthy controls, while the expression levels of CD3ζ was lower in responders as compared to nonresponders and healthy volunteers. Conclusion: Chronic HCV patients harbor high numbers of MDSCs, which are higher in nonresponders than in responders. The higher numbers of MDSCs associated with increases in the suppressing factors.

Increases in the numbers of cells with the phenotype of myeloid-derived suppressor and regulatory T cells in children with acute lymphoblastic leukemia

Background Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children. The precise mechanisms behind the relapse in this disease are not clearly known. One possible mechanism could be the accumulation of regulatory cells including myeloid-derived suppressor cells (MDSCs) and T regulatory cells (T regs ) which we and others have reported to mediate suppression of anti-tumor immune responses. Few previous studies investigated the roles of T reg cells in ALL, while no studies reported the emergence of MDSCs in ALL. Aim Therefore, we aimed to analyze the frequencies and phenotype of these cells in a group of Egyptian B-ALL pediatric patients (n=45). Materials and methods MDSCs were identified as Lin − HLA-DR − CD33 + CD11b + ; and T reg cells as CD4 + CD25 + CD127 −/low using multiparametric flow cytometer. Results We found significant increases in the numbers of MDSCs and T reg cells in B-ALL patients as compared to healthy control volunteers. B-ALL patients showed significant increased numbers of MDSCs and T regs before chemotherapy when compared to healthy volunteers. The numbers of MDSCs were more increased while the numbers of T reg cells were more decreased in patients during induction of chemotherapy. The highest increase in the numbers of MDSCs was observed in patients after induction of chemotherapy, while T reg cells showed the most significant decreased numbers after induction of chemotherapy. Conclusion Our results indicate that B-ALL patients harbor both MDSCs and T reg cells, opening a new avenue to investigate the mechanism mediating the emergence of these cells in larger numbers of patients at different treatment stages.

Study of peripheral stem cells mobilization as a treatment line of pediatric dilated cardiomyopathy

BACKGROUND Mobilizing hematopoietic stem cells may be a promising intervention for the treatment of idiopathic dilated cardiomyopathy (IDCM) in infant and children. So the aim of the work is to evaluate the efficacy of granulocyte-colony stimulating factor (G-CSF) as a therapeutic modality in pediatric IDCM. METHODS A randomized clinical trial was conducted on 40 pediatric patients with IDCM. They were subjected to history taking, clinical examination, serum lactate dehydrogenase (LDH), total creatinine phosphokinase (CPK), creatinine phosphokinase isoenzyme B (CK-MB) isoenzyme, and peripheral blood CD34(+) cell assessment before and at day 7 after subcutaneous G-CSF injection for 5 consecutive days. Echocardiography was done before and 1, 3 and 6 months after therapy. RESULTS Clinical improvement in the form of regression of patients Modified Ross heart failure (MRHC) classification classes. Increased percentage of CD34(+) mobilized cells from the bone marrow, and significant increase in blood counts especially white blood cells 7 days after G-CSF injection. Significant improvement was found in echocardiographic data evaluating systolic function of the heart [Ejection fraction, Fractional shortening and systolic velocity at mitral annulus (Sm)]. CONCLUSIONS Administration of G-CSF may be beneficial in improving systolic functions of the heart in pediatric IDCM and more studies with a large number of patients are needed.