Altered Pattern of Naive and Memory B cells and B1 Cells in Patients with Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder characterized by a greatly increased susceptibility to severe fungal and bacterial infections caused by defects in NADPH oxidase of phagocytic cells. We aimed to investigate immunophenotype alterations of naive and memory B cells and B1a cells in peripheral whole blood from Iranian patients with CGD. Flow cytometric analysis was performed on peripheral blood samples from 31 CGD patients and 23 healthy controls (HC) to study naive (IgD+/CD27-), memory (CD27+) B and B1a (CD5+) cells. Soluble CD27 (sCD27) and immunoglobulins were also measured by ELISA and the nephelometric method, respectively. We found significantly higher levels of naive B cells and B1a cells but lower levels of memory B cells in CGD patients compared to HC. There was no significant difference in soluble CD27 (sCD27) alteration between CGD patients and HC. Our findings suggested a role for NADPH oxidase in process of B cell differentiation and impairing conversion of naive B cells to memory B cells and altered B1a cells in CGD patients. Increased susceptibility of CGD patients to opportunistic infections and autoimmune disorders could be partly explained by the altered phenotype of B lymphocytes in these patients

Global systematic review of primary immunodeficiency registries

Introduction During the last 4 decades, registration of patients with primary immunodeficiencies (PID) has played an essential role in different aspects of these diseases worldwide including epidemiological indexes, policymaking, quality controls of care/life, facilitation of genetic studies and clinical trials as well as improving our understanding about the natural history of the disease and the immune system function. However, due to the limitation of sustainable resources supporting these registries, inconsistency in diagnostic criteria and lack of molecular diagnosis as well as difficulties in the documentation and designing any universal platform, the global perspective of these diseases remains unclear. Areas covered Published and unpublished studies from January 1981 to June 2020 were systematically reviewed on PubMed, Web of Science and Scopus. Additionally, the reference list of all studies was hand-searched for additional studies. This effort identified a total of 104614 registered patients and suggests identification of at least 10590 additional PID patients, mainly from countries located in Asia and Africa. Molecular defects in genes known to cause PID were identified and reported in 13852 (13.2% of all registered) patients. Expert opinion Although these data suggest some progress in the identification and documentation of PID patients worldwide, achieving the basic requirement for the global PID burden estimation and registration of undiagnosed patients will require more reinforcement of the progress, involving both improved diagnostic facilities and neonatal screening.Peer reviewe

The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells

Abstract The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays critical roles in orchestrating of immune system, especially cytokine receptors and they can modulate the polarization of T helper cells. This pathway is regulated by an array of regulator proteins, including Suppressors of Cytokine Signaling (SOCS), Protein Inhibitors of Activated STATs (PIAS) and Protein Tyrosine Phosphatases (PTPs) determining the initiation, duration and termination of the signaling cascades. Dysregulation of the JAK-STAT pathway in T helper cells may result in various immune disorders. In this review, we represent how the JAK-STAT pathway is generally regulated and then in Th cell subsets in more detail. Finally, we introduce novel targeted strategies as promising therapeutic approaches in the treatment of immune disorders. Studies are ongoing for identifying the other regulators of the JAK-STAT pathway and designing innovative therapeutic strategies. Therefore, further investigation is needed

Increased production of nitric oxide by neutrophils from patients with chronic granulomatous disease on interferon-gamma treatment

Chronic granulomatous disease (CGD) is a rare immunodeficiency disorder in which phagocytic leukocytes fail to generate superoxide (O-2(-)) and antimicrobial oxidants. The therapeutic validity of interferon-gamma (IFN-gamma) has been well established in CGD patients but its underlying mechanisms remain poorly understood. One probable mechanism has been suggested to be modulation of nitric oxide (NO) release from phagocytic cells. Herein, we investigated NO production from neutrophil cells in CGD patients on treatment with IFN-gamma in vivo and in vitro. We measured NO levels in sera from 19 CGD patients (group I: 7 patients treated with TMP-SMX, group II: 12 patients treated with TMP-SMX and IFN-gamma simultaneously) and healthy control individuals (8 cases). We also measured NO production from neutrophils in both patients groups as well as in control group after adding 100 U IFN-gamma in vitro. Our results showed that there was a significant difference between the groups in the NO levels of serum; patients who received IFN-gamma had significantly higher amount of NO than the other groups. Besides, NO levels increased significantly after adding 100 U IFN-gamma in vitro in three studied groups, considerably in the patients on treatment with IFN-gamma. As a brief conclusion, the effect of IFN-gamma in increasing NO production is obvious. This could be an explanation for the therapeutic effect of IFN-gamma in patients with CGD as NO acts as a bactericidal agent and plays a role in host defense mechanism instead of O-2(-). (C) 2012 Elsevier B.V. All rights reserved

Enhancing of Wound Healing in Burn Patients through Candida albicans β-Glucan

The mortality and disability-adjusted life years (DALYs) of burn patients are decreasing over time. However, finding novel effective treatment approaches using natural agents is highly considered to reduce the burden of burn injuries. One of the recent agents used in wound healing is β-glucan, mainly extracted from fungi cell walls. This study aimed to evaluate the effect of 5% (m/m) of yeast β-glucan ointment on burn wound healing and to assess the impact of β-glucan on cytokines during the treatment. Thirty-three patients with second or third-degree burns were enrolled in this study. Two groups of twenty-three and ten patients used yeast 5% (m/m) β-glucan ointment (study group) and Stratamed ointment (control), respectively, on a daily basis, for a maximum of four weeks. The size of the burn wounds was measured before and at the end of the treatment. Blood samples of 14 and 10 patients in the β-glucan and control groups, respectively, were obtained before and after the treatment, and the enzyme-linked immunosorbent assay (ELISA) was performed to measure the serum concentration of the IL-4, IL-17, and IFN-γ cytokines. The log-binomial model was used to assess the efficacy of the β-glucan ointment on burn wound healing. ANOVA/ANCOVA was employed to assess the effects of β-glucan on the serum concentration of cytokines. After adjusting for potential confounders/covariates, patients receiving β-glucan had better wound healing (RR = 4.34; 95% CI: 0.73 to 25.67; p = 0.11). There was a significant difference in IL-4 secretion between the β-glucan and control groups after adjusting for potential confounders/covariates (MD = 77.27; 95% CI: 44.73 to 109.82; Cohen’s d = 2.21; 95% CI: 1.16 to 3.24; p = 0.0001). The results indicate that 5% (m/m) of β-glucan has efficacy in burn wound healing, and a significant difference was found in the level of IL-4 after receiving β-glucan. Further studies with a two-arm design and long-term use of ointment are needed to confirm the effect of β-glucan on wound healing and cytokine secretion