The impact of PD-1/PD-L1, CTLA-4, TIM-3 and LAG-3 immune checkpoint receptor expression in the development of acute graft versus host disease (aGVHD) and disease recurrence after allogeneic hematopoietic stem cell transplantation.

The immune checkpoint receptors play a crucial role in managing the transplantation outcome including development of acute graft versus host disease (aGVHD) and disease recurrence following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is well established. This study aimed to investigate the expression of immune checkpoint receptors, including PD-1/PD-L1, CTLA-4, TIM-3, and LAG-3 in donors, as well as changes in their expression during the first 90 days (day 30 and day 90) post-HLA-matched allo-HSCT, concerning the development of aGVHD and disease relapse. Forty-one donor/recipient pairs were included in this study.

Abnormal frequency of the memory B cell subsets and plasmablasts in patients with congenital severe hemophilia A: correlation with "Inhibitor" formation.

Background: Development of antibodies against infused Factor VIII (FVIII) or "inhibitors" represents a major challenge following FVIII replacement therapy in patients with hemophilia A (HA). Recent studies have shown that certain cellular compartments of the immune system contribute to the production of such antibodies. Herein, we determined the frequency of class-switched CD19IgDCD27/non-class-switched CD19IgDCD27 memory B cell subsets and CD19CD27CD38 plasmablasts in patients with severe HA and their association with the development of inhibitors in these patients.

Altered frequency of FOXP3 regulatory T cells is associated with development of inhibitors in patients with severe hemophilia A.

Introduction: The development of anti-factor VIII (FVIII) antibodies or "inhibitors" is a major complication following FVIII replacement therapy in patients with severe hemophilia A (HA), rendering the treatment inefficient. Data on the role of regulatory T cells (Tregs) in inhibitor formation in these patients are rare. Herein, we aimed to investigate whether a difference in the FOXP3 Tregs is linked to the formation of the inhibitors in severe HA patients.

Selenium Supplementation Alter the Frequency of Th17 but not Th1/Th2 Lymphocytes in Diffuse Large B Cell Lymphoma Patients.

Background: Selenium (Se) is a micronutrient, which has recently been proven to have a positive effect on the immune system of cancer patients, but the underlying mechanism is not clearly defined. In this randomized controlled trial, we evaluated the effect of three-month Se supplementation on the profile of CD4+ T-helper subsets including IFN-γ+/IL-4- Th1, IFN-γ-/IL-4+ Th2, and CD4+IL-17+ Th17 cells in sixteen diffuse large B cell lymphoma (DLBCL) patients at stable remission phase who consumed Se (Se+) compared to the fourteen control patients who did not receive Se (Se-).

Methods: The frequency of IFN-γ+/IL-4- Th1, IFN-γ-/IL-4+ Th2, and CD4+IL-17+ Th17 lymphocytes was determined using a four-color flow cytometry method.

Atopy manifestations in pediatric patients with acute lymphoblastic leukemia: correlation assessment with interleukin-4 (IL-4) and IgE level.

Background: Acute lymphoblastic leukemia (ALL) is the most common type of cancer in the age range of under 15 years old and accounts for 25-30% of all childhood cancers. Although conventional chemotherapy regimens are used to improve the overall survival rate, it has been associated with some complications, amongst which allergic manifestations with unknown mechanisms are more common.

Methods: Our study compared serum IgE and IL-4 concentration, as a hallmark of allergic responses in pediatric ALL patients before and after 6 months of intensive (high-dose) chemotherapy, to show whether changes in the level of these markers may be associated with atopy.

The prognostic significance of immune checkpoint receptor expression in patients with lymphoma: Association with disease status and clinical outcomes.

Introduction: Little is known about the expression of immune checkpoint receptors in the peripheral blood of lymphoma patients. Herein, we assessed the expression of inhibitory checkpoint receptors, including CTLA-4, PD-1/PDL-1, LAG-3, and TIM-3 in the peripheral blood of lymphoma patients and its correlation with the clinical outcomes of patients. Therefore, 47 classical Hodgkin lymphoma (cHL), 48 non-Hodgkin lymphoma patients with diffuse large B-cell lymphoma (DLBCL) subtype, and 30 healthy controls were recruited.

Study of the Serum Immunoglobulin and Cell-Mediated Immunity in Patients with Congenital Severe Hemophilia.

Background: It has been shown that a close relationship exists between the immune system and coagulation cascade. Hemophilia A is an X-linked, recessive bleeding disorder caused by deficiency of functional plasma clotting factor VIII that is classically treated with factor VIII replacement therapy. Despite this, some patients produce inhibitors or antibodies against epitopes of infused factor VIII, indicating the activation of the adaptive immune system.

Expression of the immune checkpoint receptors CTLA-4, LAG-3, and TIM-3 in β-thalassemia major patients: correlation with alloantibody production and regulatory T cells (Tregs) phenotype.

Alloimmunization is a serious complication in β-thalassemia major patients as a result of repeated blood transfusion. The immune checkpoint receptors play an important role in regulating immune system homeostasis and the function of the immune cells. This study aimed to evaluate the expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), lymphocyte activation gene 3 (LAG-3), and T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) immune checkpoint molecules in β-thalassemia major patients with and without alloantibody.

The impact of selenium on regulatory T cell frequency and immune checkpoint receptor expression in patients with diffuse large B cell lymphoma (DLBCL).

For many decades, selenium (Se) has been known as a potential anti-cancer agent that can also improve the function of immune cells in a variety of solid tumors. However, there is no report on the role of Se on CD4 T cell subsets like CD4CD25FOXP3 regulatory T cells (Tregs) in lymphoma patients. In this randomized clinical trial, we investigated the effect of 3-month Se consumption on the frequency of CD4CD25FOXP3 Tregs and the expression of immune checkpoint receptors in thirty-two non-Hodgkin lymphoma (NHL) patients (16 patients with Se (Se+) and 16 without Se (Se-) consumption) with diffuse large B-cell lymphoma (DLBCL) subtype at stable remission.

Higher Peripheral Blood IFN-γ-/IL-4+ Th2 Lymphocytes Are Associated with Lower Rate of Relapse in Patients with Lymphoma.

Background: The role of T-helper lymphocytes especially T helper 2 (Th2) subsets in lymphoid malignancies is debatable and unknown.

Methods: Herein, we evaluated the polarization of the IFN-γ/IL-4 Th1 and IFN-γ/IL-4 Th2 lymphocytes in 95 lymphoma patients including 47 classical Hodgkin's lymphoma (cHL) and 48 diffuse large B cell lymphoma patients (DLBCL) at different disease phases and its correlation with the clinical outcomes of patients using flow cytometry method.

Results: The proportion of IFN-γ/IL-4 Th1 lymphocytes was significantly higher in cHL patients at remission compared to the newly diagnosed ones.

Association of killer-cell immunoglobulin-like receptor genes with acute myelogenous leukaemia.

Killer-cell immunoglobulin-like receptors (KIRs) are important because of their key roles in NK cell development and function. Some KIR genes have been associated with the incidence of haematological malignancies. This study was designed to determine whether the inheritance of specific KIR genes is associated with susceptibility to acute myelogenous leukaemia (AML) in Persians living in south-western Iran.

Aberrant peripheral blood CD4 CD25 FOXP3 regulatory T cells/T helper-17 number is associated with the outcome of patients with lymphoma.

Little is known about the clinical significance of the peripheral blood CD4 CD25 FOXP3 regulatory T cells (Tregs) and T helper-17 (Th17) cells in lymphoma patients. In this study, the prognostic and clinical significance of peripheral blood Tregs and Th17 cells were evaluated in lymphoma patients during different phases. The frequency of Tregs and Th17 lymphocytes was measured by flow cytometry method in 47 classical Hodgkin's lymphoma (cHL) and 48 diffuse large B cell lymphoma (DLBCL) patients.

Aberrant Expression of the miR-181b/miR-222 after Hematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia.

Recently, dysregulated expression of various micro RNAs has been reported in hematologic malignancies, especially AML disease which affects normal hematopoiesis in these patients and thereby contribute to clinical outcome of AML patients, associated with either poor or favorable prognosis. Herein, we evaluated the expression of miR-181b and miR-222 in acute myeloid leukemia patients and correlation with response to therapy after hematopoietic stem cell transplantation. Eighty newly diagnosed AML patients and 80 healthy controls were recruited.

Overexpression of indoleamine 2,3-dioxygenase correlates with regulatory T cell phenotype in acute myeloid leukemia patients with normal karyotype.

Background: Production of immunosuppressive enzymes such as indoleamine 2,3-dioxygenase (IDO) is one of the strategies employed by hematologic malignancies, including acute myeloid leukemia (AML), to circumvent immune surveillance. Moreover, IDO has the ability to convert CD4CD25 conventional T cells into regulatory T cells (Tregs). In this study, we evaluated the expression of IDO in cytogenetically normal acute myeloid leukemia (CN-AML) patients and its correlation with the Treg marker, FOXP3, as well as clinical and laboratory parameters.

Genetic Variation of Costimulatory Molecules, Including Cytotoxic T-Lymphocyte Antigen 4, Inducible T-Cell Costimulator, Cluster Differentiation 28, and Programmed Cell Death 1 Genes, in Iranian Patients With Leukemia.

Objectives: There are limited studies about the possible relationship between genetic variations of costimulatory genes and susceptibility to hematologic malignancies like leukemia and lymphoma.

Materials And Methods: This cross-sectional study included 59 leukemia patients. The polymorphisms of costimulatory molecules, including the CTLA-4 gene (-318 C/T, -1722 T/C, -1661 A/G, +49 A/G), PD-1 gene (1.

Association Between Cytotoxic T-Lymphocyte Antigen 4 Gene Polymorphisms and Torque Teno Virus Infection After Hematopoietic Stem Cell Transplantation.

Objectives: An association between costimulatory molecule gene polymorphisms and viral infection after hematopoietic stem cell transplantation may be related to clinical outcomes, especially acute graft-versus-host disease. Cytotoxic T-lymphocyte antigen 4 has been suggested as a crucial negative regulator of the immune system. In this study, our objective was to investigate the association between cytotoxic T-lymphocyte antigen-4 gene polymorphisms (including -1722 T/C, -1661 A/G, -318 C/T, and +49 A/G) and torque teno virus infection after hematopoietic stem cell transplantation in patients with and without acute graft-versus-host disease.

FMS-Like Tyrosine Kinase 3 (FLT3) and Nucleophosmin 1 (NPM1) in Iranian Adult Acute Myeloid Leukemia Patients with Normal Karyotypes: Mutation Status and Clinical and Laboratory Characteristics.

Objective: In this study, we evaluated the frequency of FMS-like tyrosine kinase 3 (FLT3-ITD and FLT3-TKD) and nucleophosmin (NPM1) mutations in Iranian patients with cytogenetically normal acute myeloid leukemia (CN-AML). The clinical and laboratory characteristics were compared between wild-type and mutant cases.

Materials And Methods: Seventy newly diagnosed de novo AML patients were recruited at the time of diagnosis prior to chemotherapy; among them, 54 had CN-AML.

Efficacy of Deferasirox (Exjade®) in Modulation of Iron Overload in Patients with β-Thalassemia Intermedia.

Because of insufficient erythropoiesis, peripheral hemolysis and increased gastrointestinal iron absorption, iron overload is still a matter of debate in β-thalassemia intermedia (β-TI) patients, which can be overcome using iron chelators. However, data on use of iron chelators in β-TI patients is highly restricted. The aim of this study was to evaluate the efficacy of oral administration of deferasirox (Exjade(®) or DFX) by assessment of serum ferritin levels in β-TI patients.

Polymorphism in Exon 2 of CD1 Genes in Southwest of Iran.

Background: The CD1 family is less variable transmembrane antigen presenting molecules related to the MHC molecules. CD1a and CD1e genes are the most polymorphic ones associated with autoimmune diseases. The aim was to better clarify the map of CD1 genes in Southwest Iranian normal population for implications in vaccine design.

Alteration in frequency and function of CD4⁺CD25⁺FOXP3⁺ regulatory T cells in patients with immune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder characterized by production of auto-antibodies against platelet antigens. It is obvious that regulatory T cells (Tregs) have a major role in controlling immune homeostasis and preventing autoimmunity.To investigate the frequency and functions of Tregs, twenty ITP patients and twenty age- and sex-matched healthy controls were recruited.

Evaluation of CD4+CD25+FOXP3+ regulatory T cells function in patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is one of the predominant antibody disorders where abnormalities in regulatory T cells (Tregs) may result in autoimmunity and chronic inflammation. To evaluate Tegs frequency and function, 13 CVID patients and 10 age- and sex-matched healthy volunteer were enrolled. The percentages of Tregs were calculated using flow cytomety method.

Intercellular adhesion molecule-1 genetic markers (+241G/A and +469A/G) in Iranian women with breast cancer.

Breast cancer is the most common cancer among women, the second-most leading cause of women's death after lung cancer. ICAM-1 is a cell adhesion molecule that belongs to the Ig-superfamily, with a glycoprotein structure playing a key role in leukocyte recruitment into inflammatory sites, as well as in leukocyte activation and effector function. Proteolytic cleavage of ICAM-1 results in the formation of a soluble form, sICAM-1, which is present in low-serum levels in healthy individuals but becomes elevated in inflammatory and malignant conditions.