Iranian Journal of Allergy, Asthma and Immunology

Research Progress of Immune Mechanisms Related to Persistent HPV Infection in CIN after Cervical Conization

Jingyi Yang, Fengxia Xue — Sun, 06 Oct 2024 00:00:00 +0330

Persistent human papillomavirus (HPV) infection is associated with the grading of cervical intraepithelial neoplasia (CIN), high-risk HPV infection, multiple HPV infections, high HPV load, HPV infection of surgical margin, and age in CIN after conization. The immune mechanism is complex and is primarily related to vaginal microecology disorders, immune escape, immune response impairment, and the release of regulatory cytokines. Currently, the treatment methods for postoperative persistent HPV infection include surgical treatment, antiviral treatment, vaccination, and other approaches.

Serum Galectin-3 Level in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-analysis

Sun, 06 Oct 2024 00:00:00 +0330

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial tissue transformation and fibroblast-like synoviocyte (FLS) proliferation. Galectin-3 is gaining attention as a diagnostic and prognostic biomarker for RA diagnosis. Elevated levels of Galectin-3 cause RA-FLSs to stimulate and generate proinflammatory agents, contributing to cartilage degradation and osteoclast formation. This systematic review and meta-analysis aimed to evaluate published evidence and support future investigation of Galectin-3 as an early biomarker for RA.
A systematic search was performed through four databases, including PubMed, the Web of Science, Scopus, and Embase, to find the studies examining Galectin-3 in individuals with RA compared to healthy controls. The risk of bias was evaluated using the Newcastle-Ottawa Quality Assessment Scale. Random-effects meta-analysis comparing serum/plasma Galectin-3 levels between individuals with RA and healthy control groups was performed to determine the standardized mean differences (SMD) along with 95% confidence intervals.
Following the initial search, studies went through screening. 12 studies, involving 773 patients with RA and 411 healthy controls, were included. Meta-analysis of the included studies revealed that individuals with RA had significantly higher levels of circulatory Galectin-3 compared to healthy control groups (SMD 0.957, 95% CI 0.393 to 1.520). Univariable meta-regression showed no significant association between age, publication year, sample size, or the male percentage with effect size.
According to the results, Galectin-3 might be useful as a biomarker for RA. To support these findings, further investigations of Galectin-3 as a possible early biomarker of RA is necessary.

Effect of Air Pollutants and Environmental Noise on the Childhood Asthma Prevalence in Tehran, Iran

Sun, 06 Oct 2024 00:00:00 +0330

The purpose of this study is to investigate the effect of air pollutants and noise on the prevalence of childhood asthma in Tehran, Iran.
The standardized questionnaire was completed by one of the parents of children aged 6–7 years or by adolescents aged 13–14 years.
The asthma prevalence in ages 6-7 and 13–14 was found to be 8.8% and 17.44%, respectively. A significant positive association was observed between “ever wheezing” and monoxide carbon (CO) concentration (OR=1.84, 1.05-3.25 in 13–14 years), the occurrence of 4 to 12 wheezing attacks and sulfur dioxide (SO₂) concentration (Odds Ratio (OR)=1.39, 1.04-1.91) and particulate matter less than 2.5 micron (PM_2.5) concentration (OR=1.38, 1.05-1.98 and OR=1.13, 0.98-1.39 in 6-7 and 13–14 years, respectively), as well as one night per week of sleep disturbances and nitrogen dioxide (NO₂) concentration (OR=1.09, 1.03-1.16 in 6–7 years, respectively). It was also found that there was a significant interaction between the noise level and particulate matter less than 10 micron (PM₁₀) level.
Based on the findings, exposure to certain outdoor air pollutants and noise can affect prevalence of asthma symptoms in residence of Tehran. The simultaneous presence of air pollutants and noise has an aggravating effect on the prevalence of asthma symptoms. Therefore, controlling sources of pollutants for reducing asthma symptoms is suggested.

Risk Factors and Comorbidities of Recurrent Nasal Polyposis

Sun, 06 Oct 2024 00:00:00 +0330

Chronic rhinosinusitis is divided into two groups, which are Chronic rhinosinusitis with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP). The rate of post-surgical recurrence in the CRSwNP is high, and predicting factors are unknown. This study aims to identify and evaluate risk factors associated with treatment-resistant and recurrent CRSwNP.
This cross-sectional study evaluates demographic data and atopic risk factors in patients with CRSwNP, including a high IgE level (≥100 U/mL), skin prick test (SPT) for aeroallergens, aspirin-exacerbated respiratory disease (AERD), and asthma prevalence. An oral aspirin challenge was performed to diagnose AERD. 191 patients with CRSwNP were enrolled, with 73 patients in the recurrent, and 118 patients in the non-recurrent group. The mean age of the patients in the recurrent group was 45.08±12.05. The mean age of the patients in the non-recurrent group was 42.89±11.73. 49. Asthma prevalence in recurrent- CRSwNP is significantly higher than non-recurrent CRSwNP Asthma severity in recurrent CRSwNP and AERD patients was significantly higher than in nonrecurrent CRSwNP and non-AERD patients. The level of IgE in the recurrent- CRSwNP is higher than non-recurrent CRSwNP. Positive SPT results for tree, weed, and mite allergens were higher in the non-recurrent- CRSwNP group compared to the recurrent CRSwNPgroup.
Asthma had a significantly higher difference in AERD compared to non-AERD. The level of IgE in AERD is higher than non-AERD.
Recurrent CRSwNP patients and AERD patients had Higher IgE levels. Asthma is more prevalent and more severe in both AERD and recurrent CRSwNP. However, a positive SPT result has been seen higher in non-recurrent CRSwNP.

High Expression of Immune Checkpoint Molecules in Different Types of Thyroid Cancer

Sun, 06 Oct 2024 00:00:00 +0330

This study aimed to investigate the expression of programmed cell death protein-1 (PD-1) and its ligand (PD-L1) immune checkpoint molecules in thyroid carcinomas and determine their association with the clinicopathological characteristics of patients.
Thyroid tissue specimens from 100 patients diagnosed with primary thyroid carcinomas including papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC) were collected. Sections were prepared from formalin-fixed paraffin-embedded samples, and PD-1 and PD-L1 expressions were examined using immunohistochemistry.
PD-1 was detected in tumor-infiltrating lymphocytes (TILs) in 88% of the patients and tumor cells in 28% of the patients with 10% in PTC, 5% in FTC, 5% in MTC, and 8% in ATC). PD-L1 was found in tumor cells and TILs in 30% and 79% of the patients, respectively. Moreover, a significant difference was observed in PD-1 and PD-L1 expression between tumor cells and TILs across different tumor types. However, their expression in tumor cells and TILs was significantly higher in ATC compared to other tumor types. Additionally, the expression of PD-1 and PD-L1 was significantly associated with an advanced stage, higher tumor size, tumor necrosis, and mitosis. A significant positive correlation was also observed between the expression of PD-1 and PD-L1 in tumor cells and TILs.
The higher expression of PD-1 and PD-L1 may contribute to tumor progression. Therefore, combinational immunotherapy by these immune checkpoint inhibitors might be a promising strategy for clinical improvement in patients with thyroid cancer, especially those with ATC.

The Immunomodulatory Effects of Curcumin on Forkhead Box O1 and MicroRNA-873 in Patients with Osteoarthritis

Sun, 06 Oct 2024 00:00:00 +0330

Osteoarthritis (OA) is among the most prevalent articular disorders, whose incidence is directly related to aging. Due to the antiinflammatory potential of curcumin as the active component of turmeric, the present study evaluated the effects of curcumin on the expression of genes related to T helper 17 (Th17), including forkhead box p3 (FOXP3), forkhead box o1 (FOXO1), transforming growth factor-β (TGFB1) and microRNA-873, human (HSA-MIR-873), in OA patients.
Female patients with knee OA (n=30) were randomly categorized into 2 groups, including the intervention group who received curcumin (n=15) and the placebo (n=15) in a double-blind clinical trial for 3 months. The expression of FOXO1, FOXP3, TGFB1, and HSA-MIR-873 genes was evaluated by SYBR Green real-time reverse transcription polymerase chain reaction.
In the curcumin group, FOXO1 gene expression was significantly increased, while the increase in FOXP3 gene expression was not significant. Moreover, the expression level of the HSA-MIR-873 gene showed a significant increase in the curcumin group.
The modulatory effects of curcumin on Th17 function might be associated with the expression of FOXO1 and HSA-MIR-873 genes.

Mechanism of PD-1/PD-L1 in Regulating cTfr/cTfh Balance in Patients with Rheumatoid Arthritis

Xiuzhen Wang, Caijie Liu — Sun, 06 Oct 2024 00:00:00 +0330

Rheumatoid arthritis (RA) is frequent, an imbalance between helper cells (Th) and regulatory T cells (Treg) is the fundamental immunological cause of RA. This study investigates how recombinant human programmed cell death 1 (PD-L1) protein affects circulating T follicular helper (cTfh), circulating T follicular regulatory (cTfr), and their equilibrium.
Magnetic bead sorting was used to select CD4+CXCR5+T cells from RA patients' and healthy individuals' peripheral blood mononuclear cells for in vitro growth. Recombinant human PD-L1 protein stimulated CD4+CXCR5+T cells. Cell counting kit 8 (CCK-8), flow cytometry surface labeling, ELISA, and RT-PCR were used to measure CD4+CXCR5+T cell proliferation inhibition, cTfh and cTfr frequencies, IL-21 expression, and PI3K, AKT, Bcl-6, and Blimp-1 mRNA levels.
The recombinant human PD-L1 protein dose-dependently inhibited the proliferation of CD4+CXCR5+T cells in active RA peripheral blood. However, it has a weaker inhibitory effect on healthy peripheral blood CD4+CXCR5+T cells. PD-L1 protein decreased cTfh in active RA peripheral blood CD4+CXCR5+T overall cultured cells but did not affect cTfr; The cTfr/cTfh ratio increased but did not affect the frequency of cTfh and cTfr in healthy persons' cultured CD4+CXCR5+T cells. PD-L1 protein reduced IL-21 in CD4+CXCR5+T cell culture supernatant from active RA peripheral blood. Recombinant human PD-L1 protein lowered PI3K, AKT, and Bcl-6 mRNA in active RA peripheral blood CD4+CXCR5+T cell culture, including significant differences. But Blinmp-1 mRNA variations were neither substantial nor statistically different.
PD-1/PD-L1 limits cTfh proliferation, differentiation, and activation via the PI3K/AKT signaling pathway regulates its immunological balance with cTfr, and corrects the cTfr/cTfh imbalance by controlling their interaction.

Emodin-based Regulation and Control of Serum Complement C5a, Oxidative Stress, and Inflammatory Responses in Rats with Urosepsis via AMPK/SIRT1

Juan Cui, Shufang Wang, Sicheng Bi, Hong Zhou, Lichao Sun — Sun, 06 Oct 2024 00:00:00 +0330

Emodin, derived from Rheum officinale and aloe, is known for its diverse benefits such as anti-inflammatory, antioxidant, and antibacterial properties. Currently, the impact of emodin on urosepsis is unclear. This study aims to investigate the mechanism of action of emodin in urosepsis.
Peripheral blood mononuclear cells (PBMCs) were purchased from Cloud-Clone Animal Inc. and treated with emodin. Cell viability and the lactate dehydrogenase (LDH) level were then assessed. In a separate experiment a urosepsis model was established in Sprague Dawley rats which were subsequently treated with emodin. The levels of oxidative stress-related factors, serum complements and inflammatory factors were measured using commercial kits. Blood urea nitrogen and serum creatinine levels were determined using a fully automatic biochemical analyzer. The levels of pro-inflammatory proteins and AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRT1) pathway-related proteins were evaluated via Western blot.
PBMCs were unaffected by emodin concentrations below 60 μg/mL, and minimal LDH levels were detected in the cells. Emodin attenuated the effects of Escherichia coli and diminished the production of serum complements, oxidative stress-related proteins, and inflammatory factors in PBMCs. Notably, the effects of emodin were lessened by an AMPK pathway inhibitor. Additionally, emodin alleviated oxidative stress, complement system activation, inflammation, and kidney injury in urosepsis rats through the AMPK/SIRT1 signaling pathway.
Emodin improved kidney damage in urosepsis rats by activating the AMPK/SIRT1 signaling pathway, which reduced oxidative stress, inflammation, and complement system activation.

Mesenchymal Stem Cell Therapy Mitigates Acute and Chronic Lung Damages of Sulfur Mustard Analog Exposure

Sun, 06 Oct 2024 00:00:00 +0330

Sulfur mustard (SM) is an established chemical weapon that can result in severe damage to parts of the body. Currently, there are no effective treatments available for SM-caused damage. We aimed to investigate the therapeutic potential of adipose-derived mesenchymal stromal cells (AD-MSCs) and conditioned medium (CM-MSCs) in acute and chronic pulmonary mouse models caused by 2-chloroethyl ethyl sulfide (CEES), an SM analog.
The mice were divided into 4 experimental groups:(1) CEES+AD-MSCs, (2) CEES+CM-MSCs, (3) CEES, and (4) control. The model observation time was divided into 7 days for the short and 6 months for the long term. AD-MSCs were injected into mice via intraperitoneal injection 24 hours after CEES exposure. The therapeutic effects of AD-MSCs on pulmonary tissue damage were assessed using histopathologic assay, measuring the neutrophil count, and bronchial alveolar lavage fluid (BALF) protein level. The levels of inflammatory and anti-inflammatory cytokines were evaluated using the enzyme-linked immunosorbent assay as the outcomes of interest.
Lung damage progression was reduced by AD-MSC treatment in mice after CEES injection into the peritoneum. The proportion of CD11b⁺F4/80⁺ macrophages in peritoneum was significantly lowered by AD-MSC treatment following CEES exposure. AD-MSC administration also reduced the level of pro-inflammatory cytokines, BALF protein, and nitric oxide levels in the peritoneal cavity.
By reducing inflammation and enhancing tissue healing, AD-MSCs and CM-MSC help prevent acute lung damage caused by CEES. The current study supports the use of a mouse model as a solid experimental foundation and indicates potential use for future cell treatment.

The Role of Extracellular Vesicles Derived from MicroRNA-146a–modified Mesenchymal Stem Cells in Modulating Inflammation in Experimental Glenohumeral Osteoarthritis

Baotao Cao, Guangyuan Liu, Kai Gao, Wenqi Fan, Wei Zhao, Baibai Wang — Sun, 06 Oct 2024 00:00:00 +0330

Glenohumeral osteoarthritis (GOA) is characterized by chronic inflammation leading to joint damage. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) are promising therapies because of their immunomodulatory functions. The anti-inflammatory effects of EVs from human Adipose-derived MSCs (hADSCs) overexpressing microRNA (miR)-146a were investigated in experimental GOA in this study.
hADSCs were transfected with a mimic negative control or miR-146a mimics. GOA was induced in C57/Bl6j mice, and subsequently, the animals were treated intra-articularly with phosphate-buffered saline, miR-146a EVs, or miR-control EVs. The expression of miR-146a and its targeted cytokines interleukin (IL)-4, IL-10, tumor necrosis factor-alpha (TNF-α), IL-17, and interferon-gamma (IFN-γ) were analyzed in the spleen of mice by enzyme-linked immunosorbent assay and in the articular cartilage by real-time polymerase chain reaction.
miR-146a EVs showed enrichment of miR-146a. In GOA mice, miR-146a EV treatment significantly reduced expression levels of inflammatory cytokines IFN-γ, IL-17, and TNF-α and increased the anti-inflammatory cytokine IL-10 and IL-4 compared to controls. miR-146a EV treatment raised the anti-inflammatory cytokines and reduced the pro-inflammatory cytokines of the spleen in treated mice.
This study demonstrates that EVs derived from hADSCs overexpressing miR-146a have enhanced anti-inflammatory potential in GOA by modulating cytokine expression and production. EVs engineered with inflammation-related miRNAs could be a cell-free therapeutic approach for GOA.

Mendelian Susceptibility to Mycobacterial Disease with Signal Peptide Peptidase-like 2A (SPPL2A) Deficiency: A Case Report

Hossein Esmaeilzadeh, Gholamreza Pouladfar, Mohammad Amin Gholami, Hasan Mohtadi — Sun, 06 Oct 2024 00:00:00 +0330

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by immunodeficiency, leading to increased susceptibility to mycobacterial infections. Studies have identified several genes that are associated with MSMD in the interferon-gamma/interleukin (IL)-12/IL-23 signaling pathway.
One of these genes is signal peptide peptidase-like 2A (SPPL2A), which is very rare, and defects in this gene have been reported only in 3 patients with MSMD. This case report presents the rare SPPL2A deficiency with an abnormal presentation, which adds to the limited number of these genetic defects.
This report presents the case of a 1-year-old boy who developed Bacillus Calmette-Guerin infection (BCGitis), lymphadenopathy, and an arm abscess that required surgical drainage following BCG vaccination. The patient had hypogammaglobulinemia, normal B-cell counts, normal CD4 counts, low CD8 counts, and SPPL2A deficiency, which is related to MSMD. The patient received a second line of anti-tuberculosis agents.
SPPL2A deficiency is associated with MSMD and can cause severe BCGitis and disruption of immunoglobulin production.

Nephrotic Syndrome and Recurrent Infection

Sun, 06 Oct 2024 00:00:00 +0330

Nephrotic syndrome is characterized by the leakage of protein from the blood into the urine along with the triad of proteinuria, albuminuria, and peripheral edema. Loss of protein leads to the loss of immunoglobulin and complements. X-linked agammaglobulinemia (XLA), or Bruton disease, is a primary immunodeficiency disease caused by a defect in the development of B cells in the bone marrow and a low serum level of immunoglobulins. The present case involves a 12-year-old boy with nephrotic syndrome, osteomyelitis, and recurrent infections. We discovered that he had XLA. This report underscores the importance of considering inborn errors of immunity in cases of protein loss, such as nephrotic syndrome.