A modified schedule of multiple aeroallergen ultra-rush immunotherapy in perennial allergic rhinitis: safety, efficacy, and T lymphocyte cell population studies.

BACKGROUND: This study assessed whether a modified immunotherapy schedule for allergic rhinitis could be safe and efficient. Ultra-rush immunotherapy (URIT) rapidly desensitizes patients to aeroallergens. OBJECTIVE: We aimed to develop a modified URIT protocol in 3 days to achieve the target dose while observing whether it could improve this situation and decrease the time to achieve the maintenance dose. METHODS: The URIT was exercised in 21 patients with perennial allergic rhinitis. Premeditations were given to the patients 3 days prior to the immunotherapy and during the 3 days injections immunotherapy: pred nisolone, ranitidine, and Airokast/montelukast. Finally, the T cell population frequencies of patients prior to and after immunotherapy, including T helper 1, T helper 2, cytotoxic T lymphocytes, and regulatory T cells, were studied using flow cytometry. During the URIT protocol, 21 patients received 291 injections. RESULT: Six patients (28.6%) showed systemic reactions in our study. All systemic reactions occurred on the third day by the 1:1 dilution of the maintenance dose. These systemic reactions occurred in three patients after 13 injections, and the three remaining patients showed systemic reactions following the last injection. No systemic reaction was observed on the first and second day of the therapy, and the risk of systemic reaction with every injection was about 2%. Among the T cell populations, CD3+ and CD8+ cells decreased significantly. CONCLUSION: The findings emphasized that URIT, alongside premedication with a high dose of antihistamine, helped to achieve the maintenance dose and control clinical manifestations.

Exploring the role of tryptophanyl-tRNA synthetase and associations with inflammatory markers and clinical outcomes in COVID-19 patients: A case-control study.

Tryptophanyl-tRNA synthetase (WRS) is a critical enzyme involved in protein synthesis, responsible for charging tRNA with the essential amino acid tryptophan. Recent studies have highlighted its novel role in stimulating innate immunity against bacterial and viral infections. However, the significance of WRS in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains elusive. In this study, we aimed to investigate the complex interplay between WRS, inflammatory markers, Toll-like receptor-4 (TLR-4), and clinical outcomes in coronavirus disease 19 (COVID-19) patients. A case-control investigation comprised 127 COVID-19 patients, carefully classified as severe or moderate upon admission, and 112 healthy individuals as a comparative group. Blood samples were meticulously collected before treatment initiation, and WRS, interleukin-6 (IL-6), and C-reactive protein (CRP) concentrations were quantified using a well-established commercial ELISA kit. Peripheral blood mononuclear cells (PBMCs) were isolated from the blood samples, and RNA was extracted for cDNA synthesis. Semi-quantitative real-time polymerase chain reaction (PCR) was employed to assess the relative expression of TLR-4. COVID-19 patients exhibited elevated levels of WRS, IL-6, CRP, and TLR-4 expression compared to healthy individuals, with the severe group displaying significantly higher levels than the moderate group. Notably, severe patients demonstrated substantial fluctuations in CRP, IL-6, and WRS levels over time, a pattern not observed in their moderate counterparts. Although no significant distinctions were observed in the dynamic alterations of WRS, IL-6, CRP, and TLR-4 expression between deceased and surviving patients, a trend emerged indicating higher IL-6_1 levels in deceased patients and elevated lactate dehydrogenase (LDH) levels in severe patients who succumbed to the disease. This pioneering research highlights the dynamic alterations of WRS in COVID-19 patients, providing valuable insights into the correlation between WRS, inflammatory markers, and disease severity within this population. Understanding the role of WRS in SARS-CoV-2 infection may open new avenues for therapeutic interventions targeting innate immunity to combat COVID-19.

Epidemiology, Sociodemographic Factors and Comorbidity for Allergic Rhinitis, Asthma, and Rhinosinusitis Among 15 to 65-year-Old Iranian Patients.

Background: It is well established that upper and lower airways are often clumped together when diagnosing and treating a disease. This study was designed to determine the prevalence of upper and lower airway diseases and to assess the effect of sociodemographic factors on the prevalence and the comorbidity of these disorders. Methods: This cross-sectional population-based study included patients with ages ranging between 15 to 65 years, who were referred to allergy outpatient clinics in various provinces of Iran from April to September 2020. A modified global Allergy and Asthma European Network (GA2LEN) screening questionnaire was filled out by local allergists of the 12 selected provinces in Iran. Information about the patients and sociodemographic factors was also recorded. Statistical analysis was done by univariate statistical analyses and multiple logistic regressions in SPSS software Version 26. Results: Out of 4988 recruited patients, 1078 (21.6%) had the symptoms of allergic rhinitis (AR) and 285 (5.7%) met the criteria of asthma. The prevalence of acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) was 21.6 % and 22%, respectively. The highest prevalence of AR and ARS was in Tehran with the arateof of 33.9% each. Asthma was more prevalent in Khuzestan (14.2%) and CRS in Baluchestan (57.5%). Our analysis showed that the patients with asthma were most likely to have other allergic diseases as well-CRS (OR = 4.8; 95% CI, 2.02- 5.82), AR (OR= 2.5, 95% CI, 2.10-3), ARS (OR = 1.8; 95% CI, 2.10-3), followed by eczema (OR = 1.4; 95% CI, 1.13-1.67).We found that those individuals with CRS were most likely to have painkiller hypersensitivity (OR= 2.1; 95% CI, 1.21-3.83). Furthermore, smoking has been found more than 1.5 folds in patients with ARS. After adjusting variables, there was no correlation between education, occupation, and ethnicity with the studied diseases. Conclusion: Rhinosinusitis is a common condition among Iranian patients. This study confirmed that inflammation of the upper and lower airways can occur simultaneously. Gender, education, occupation, and ethnicity were found to be irrelevant in the development of either AR, asthma, ARS, or CRS.

Designing a T-cell epitope-based vaccine using in silico approaches against the Sal k 1 allergen of Salsola kali plant.

Allergens originated from Salsola kali (Russian thistle) pollen grains are one of the most important sources of aeroallergens causing pollinosis in desert and semi-desert regions. T-cell epitope-based vaccines (TEV) are more effective among different therapeutic approaches developed to alleviate allergic diseases. The physicochemical properties, and B as well as T cell epitopes of Sal k 1 (a major allergen of S. kali) were predicted using immunoinformatic tools. A TEV was constructed using the linkers EAAAK, GPGPG and the most suitable CD4+ T cell epitopes. RS04 adjuvant was added as a TLR4 agonist to the amino (N) and carboxyl (C) terminus of the TEV protein. The secondary and tertiary structures, solubility, allergenicity, toxicity, stability, physicochemical properties, docking with immune receptors, BLASTp against the human and microbiota proteomes, and in silico cloning of the designed TEV were assessed using immunoinformatic analyses. Two CD4+ T cell epitopes of Sal k1 that had high affinity with different alleles of MHC-II were selected and used in the TEV. The molecular docking of the TEV with HLADRB1, and TLR4 showed TEV strong interactions and stable binding pose to these receptors. Moreover, the codon optimized TEV sequence was cloned between NcoI and XhoI restriction sites of pET-28a(+) expression plasmid. The designed TEV can be used as a promising candidate in allergen-specific immunotherapy against S. kali. Nonetheless, effectiveness of this vaccine should be validated through immunological bioassays.

Evaluation of Allergic Reactions Following Intravenous Infusion of Polyvalent Antivenom in Snakebite Patients.

BACKGROUND: Antivenom is a gold-standard treatment for snakebite envenoming. However, adverse reactions to snake antivenom are common in many parts. OBJECTIVE: The aim of this study was to evaluate the allergic reactions following intravenous administration of antivenom sera. METHODS: This was retrospective study conducted on snakebites patients referred to the Rahimi Hospital in Khorramabad. The files of these patients were accessed for demographic data, snakebite-related data, treatment provided, clinical presentation and allergic reaction status as a result of antivenom treatment. RESULTS: 141 cases were investigated, including 73.8% male and 26.2% female patients. The mean age of the patients was 38.1±17.1 years. Age group 30-39 years accounted for the highest number of snakebite cases (24.1%). A majority of victims (89.4%) were from rural areas. Most of the patients (51.8%) were bitten in the spring and highest number of snakebite were reported in May (39.1%). The most common site of snakebite was lower extremities (50.4%) and upper extremities (44.7%). Among clinical feature of snakebite, pain was the most prevalent in 135 cases (95.7%) followed by swelling (83.7%). The mean antivenom vials used were 6.5±3.7 vials. Allergic reactions occurred in 6 patients (4.26%); reactions were mild in 5 patients and severe in 1 patient. The commonest presentation was maculopapular rash (1.4%) and the least common were headache (0.71%), nausea (0.71%), fever (0.71) and hypotension (0.71%). CONCLUSION: Snakebite is one of the significant life-threatening environmental events. Immediate antivenom treatment can reduce mortality however, patients should be carefully monitored for adverse allergic reactions.

A significant increase in expression of FOXP3 and IL-17 genes in patients with allergic rhinitis underwent accelerated rush immunotherapy.

OBJECTIVES: Allergic rhinitis (AR) is a common hypersensitivity disease worldwide. Immunotherapy has been performed as the best treatment for years. This study aimed to study the gene expression pattern of immune system cells following an accelerated rush immunotherapy protocol (ARIT) in patients with AR. MATERIALS AND METHODS: Fifteen patients with AR (15-55 years old) resident in Mashhad, Iran, with positive prick test to regional aeroallergens (weed mix, grass mix, tree mix, and Salsola) enrolled in this study. All patients were treated for three months with 3-day ARIT protocol between July 2015 and August 2016. Clinical symptoms and quality of life were recorded by two questioners. The expression levels of FOXP3, TGF-ß, IL-10, IL-17, IL-4, and IFN-γ genes in patient's peripheral blood mononuclear cells were evaluated by SYBR Green real-time RT-PCR technique. RESULTS: The severity of disease and quality of life showed significant improvement following ARIT (P-value<0.05). Gene expression of IFN-γ and IL-10 was increased whereas TGF-ß and IL-4 down-regulated, following ARIT, but these changes were not significant. However, gene expression of FOXP3 and IL-17 was significantly increased after intervention when compared with the baseline (P-value< 0.002). CONCLUSION: Significant up-regulation of FOXP3 and IL-17 genes, additionally, a significant improvement in the clinical signs following ARIT might be related to increases in HLA-DR- and FOXP3+ Treg population at the initiation phase of ARIT. Employing the flow cytometry technique to study the phenotype of these cells is suggested for future studies.

Evaluation of Sub cutaneousRush Immunotherapy Effectiveness in Perennial Allergic Rhinitis after a Year from Treatment.

INTRODUCTION: Allergen immunotherapy is an effective treatment for allergic rhinitis. Conventional immunotherapy takes at least 5 to 6 months to reach the maintenance dosage; nonetheless, rush immunotherapy accelerates to reach the maintenance dose several months earlier. However, the safety and efficacy of this treatment has not been widely investigated. The objective of the present study was to determine the efficacy of subcutaneous rush immunotherapy in the patients with perennial allergic rhinitis after a year from treatment. MATERIALS AND METHODS: This study was carried out on a total of 15 patients with allergic rhinitis who received rush immunotherapy and were evaluated for the quality of life and clinical symptoms improvement with Sino-Nasal Outcome Test Questionnaire (SNOT-22) and Mini Rhino conjunctivitis Quality of Life Questionnaire (RQLQ) before and after a year from treatment. Moreover, specific weed mix Immunoglobulin E (IgE) was measured before and after a year from treatment. Statistical analysis was performed using SPSS software (version 16) (P<0.05). RESULTS: The comparison of specific IgE indicated a significant reduction between before and after a year from treatment (P=0.005for pigweed)(P=0.022 for salsola). There was a significant decrease in clinical symptoms according to SNOT-22 Questionnaire [(mean score: 46.00, before the treatment) and (mean score: 14.06, after the treatment)]. The quality of life for most of the patients was moderate (46.7%) before the treatment and good (80%) after the treatment, which was considered statistically significant (P>0.001). CONCLUSION: Rush immunotherapy is an effective treatment in the patients with allergic rhinitis. It seems to be an alternative treatment in cases that need more rapid treatment. However, it is recommended to carry out other studies on the control group.