Exploring the potential and safety of quantum dots in allergy diagnostics.

Biomedical investigations in nanotherapeutics and nanomedicine have recently intensified in pursuit of new therapies with improved efficacy. Quantum dots (QDs) are promising nanomaterials that possess a wide array of advantageous properties, including electronic properties, optical properties, and engineered biocompatibility under physiological conditions. Due to these characteristics, QDs are mainly used for biomedical labeling and theranostic (therapeutic-diagnostic) agents. QDs can be functionalized with ligands to facilitate their interaction with the immune system, specific IgE, and effector cell receptors. However, undesirable side effects such as hypersensitivity and toxicity may occur, requiring further assessment. This review systematically summarizes the potential uses of QDs in the allergy field. An overview of the definition and development of QDs is provided, along with the applications of QDs in allergy studies, including the detection of allergen-specific IgE (sIgE), food allergens, and sIgE in cellular tests. The potential treatment of allergies with QDs is also described, highlighting the toxicity and biocompatibility of these nanodevices. Finally, we discuss the current findings on the immunotoxicity of QDs. Several favorable points regarding the use of QDs for allergy diagnosis and treatment are noted.

Clinical Course, Therapeutic Management and Outcome of Coronavirus Disease in Patients With Inborn Errors of Immunity: A Retrospective Multicenter Experience From Iran.

BACKGROUND: Inborn errors of immunity (IEIs) are characterized by defects in the structure and function of the immune system. This study was designed to assess the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on this potentially particularly susceptible group of patients. METHODS: This retrospective cross-sectional study analyzed patients from 3 referral immunodeficiency centers in Iran. The demographic, clinical, laboratory and therapeutical data of confirmed IEI patients with SARS-CoV-2 infection were collected and analyzed. RESULTS: A total of 19 IEI patients, 52.6% male and 47.4% female, with coronavirus disease 2019 (COVID-19) were enrolled. The most common diagnosed IEIs were (severe) combined immunodeficiency ((S)CID) (9, 47.4%) and predominantly antibody deficiencies (7, 36.8%). The main presenting symptoms included fever (16, 84.2%), cough (12, 63.2%), dyspnea (9, 47.4%) and myalgia (8, 42.1%). Among additional preexisting comorbidities, atopy ( P = 0.087) and renal disorders ( P = 0.087) were more strongly associated with the development of respiratory failure, although not statistically significant. SARS-CoV-2 infection was determined by polymerase chain reaction (n = 19, 100%) within a median (interquartile range) of 1 (0-6) days following admission. Among all laboratory indices, thrombocytopenia ( P = 0.009) was associated with a need for intensive care unit admission. The overall mortality rate was 36.9% and highest among (S)CID patients (4, 44.4%). CONCLUSIONS: Severe COVID-19 most frequently affected (S)CID and predominantly antibody deficiencies patients among this multicenter Iranian cohort. Further studies are required to evaluate the impact of additional preexisting comorbidities and the development of thrombocytopenia on the severity and prognosis of COVID-19 in IEIs.

Systemic aspergillosis in a patient with interferon gamma receptor 1 deficiency; a case report.

BACKGROUND: Interferon-gamma receptor deficiency is a heterogeneous spectrum of disease which involves mutations in IFNGR1, IFNGR2 genes, and the downstream signaling proteins such as STAT1. These mutations are associated with immunodeficiency 27 A and 27B, making the patient prone to mycobacterial infections. Patients with this condition are also at increased risk for affliction with viral and bacterial infections, such as with the Herpesviridae family, Listeria, and Salmonella. Moreover, SH2B3 mutation is associated with autoimmune and lymphoproliferative conditions. CASE PRESENTATION: the patient was a 19-month-old infant girl who presented with a two-week history of fever. She had near-normal flowcytometry with high IgM and IgE. She had pneumonic infiltration in her chest and right hilar and para-aortic lymphadenopathy. PCR of whole blood for Aspergillus fumigatus came back positive. In her Whole Exome Sequencing she had IFNGR1 and SH2B3 mutations. CONCLUSION: systemic fungal infections such as Aspergillosis can occur in patients with interferon-gamma receptor one deficiency. This type of immunodeficiency should be considered in treating patients with systemic Aspergillosis.

Immune checkpoint molecules in prevention and development of asthma.

Allergic asthma is a respiratory disease initiated by type-2 immune responses characterized by secretion of alarmins, interleukin-4 (IL-4), IL-5, and IL-13, eosinophilic inflammation, and airway hyperresponsiveness (AHR). Immune checkpoints (ICPs) are inhibitory or stimulatory molecules expressed on different immune cells, tumor cells, or other cell types that regulate immune system activation and maintain immune homeostasis. Compelling evidence indicates a key role for ICPs in both the progression and prevention of asthma. There is also evidence of asthma development or exacerbation in some cancer patients receiving ICP therapy. The aim of this review is to provide an updated overview of ICPs and their roles in asthma pathogenesis, and to assess their implications as therapeutic targets in asthma.

The effect of vitamin D add-on therapy on the improvement of quality of life and clinical symptoms of patients with chronic spontaneous urticaria.

BACKGROUND: Chronic urticaria is a common distressing allergic skin disorder. Immune dysregulation, histamine release and mast cell degranulation are suggested as its underlying mechanisms. OBJECTIVE: Add-on therapy of vitamin D was evaluated in patients with chronic spontaneous urticaria to determine the quality of life and urticaria severity score. METHODS: In a prospective, double-blinded study, 80 participants with chronic spontaneous urticaria were randomized to low (4200 IU/week, group 1) and high (28,000 IU/week, group 2) vitamin D3 supplementation groups for 12 weeks. Demographic data; quality of life, urticaria severity and medication scores; 25-hydroxyvitamin D and anti-thyroid peroxidase antibody levels; and autologous serum skin test data were collected. RESULTS: Both groups showed significantly reduced total urticaria severity score; decrement in group 2 score was significant compared to group 1 at week 6 (P = 0.010). Quality of life score was also significantly reduced; decrement in group 2 score was significant compared to group 1 at both weeks 6 (P = 0.005) and 12 (P = 0.007). 25-hydroxyvitamin D levels were elevated significantly over the course of 12 weeks in both groups; however, the elevation in group 2 was significantly higher than group 1 at week 12 (P = 0.002). Medication score was significantly reduced, with no significant difference between groups. No association was observed between positive autologous serum skin test, angioedema and high level of Anti thyroperoxidase antibody with positive response to vitamin D. CONCLUSIONS: Add-on therapy with vitamin D (28,000 IU/week) can be considered as a safe and potentially beneficial treatment in patients with chronic spontaneous urticaria.

A rare case of SRD5A3-CDG in a patient with ataxia and telangiectasia: A case report.

Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is an extremely rare congenital disease. Common manifestations are developmental delay, intellectual disability, ophthalmological abnormalities, cerebellar abnormalities, ataxia, and hypotonia. Here, we discuss a seven-year-old boy with SRD5A3-CDG (homozygous variant c.57G>A [p.Trp19Ter]), featuring the unprecedented finding of telangiectasia.

In Silico Evaluation of Nonsynonymous SNPs in Human ADAM33: The Most Common Form of Genetic Association to Asthma Susceptibility.

ADAM33 is a zinc-dependent metalloprotease of the ADAM family, which plays a vital biological role as an activator of Th2 cytokines and growth factors. Moreover, this protein is crucial for the normal development of the lung in the fetus two months after gestation leading to determining lung functions all over life. In this regard, mutations in ADAM33 have been linked with asthma risk factors. Consequently, identifying ADAM33 pathogenic nonsynonymous single-nucleotide polymorphisms (nsSNPs) can be very important in asthma treatment. In the present study, 1055 nsSNPs of human ADAM33 were analyzed using biocomputational software, 31 of which were found to be detrimental mutations. Precise structural and stability analysis revealed D219V, C669G, and C606S as the most destabilizing SNPs. Furthermore, MD simulations disclosed higher overall fluctuation and alteration in intramolecular interactions compared with the wild-type structure. Overall, the results suggest D219V, C669G, and C606S detrimental mutations as a starting point for further case-control studies on the ADAM33 protein as well as an essential source for future targeted mechanisms.

An unusual case of cystic fibrosis with pancytopenia due to copper deficiency and blindness caused by vitamin A deficiency: A case-report.

Cystic fibrosis (CF) is a multi-systemic autosomal recessive disease which mostly involves the respiratory, digestive, and reproductive systems, but it can present with various clinical presentations, especially in adulthood. We describe a 19-year-old boy, a known case of CF who presented with less known clinical presentations of CF, blindness, liver cirrhosis, vitamin A deficiency, and pancytopenia.

A Review of Aspirin-exacerbated Respiratory Diseases and Immunological Efficacy of Aspirin Desensitization.

Aspirin-exacerbated respiratory disease (AERD) is a chronic inflammatory disease. It is defined by asthma, chronic rhinosinusitis with nasal polyposis, and a hypersensitivity reaction to aspirin or nonsteroidal anti-inflammatory drugs. Aspirin desensitization (AD) has been confirmed as an effective treatment to control AERD inflammation through the modulation of immune responses. We aimed to review AERD with an overview of the epidemiology, pathophysiology, and treatment. We also discussed the effect of AD on immunological markers involved in AERD pathogenesis. A search of electronic databases on AERD was performed. We included five randomized clinical trials (RCTs) on AD. We also searched databases for recent studies that investigated the effect of AD on the immunological mechanisms of AERD. RCTs have demonstrated the therapeutic effectiveness of AD on the patients' quality of life, asthma symptom score, inhaled and oral steroid use, forced expiratory volume in 1 sec (FEV1), and inflammatory mediators. The clinical benefits of AD can occur though the regulation of innate and adaptive immune responses that are involved in the pathogenesis of AERD. In addition to the valuable effects of AD in RCTs, some side effects such as gastrointestinal bleeding, asthma exacerbation, or rash have been reported that should be considered for reaching an optimal protocol for AD.

Evaluation of T Cell Proliferation Using CFSE Dilution Assay: A Comparison between Stimulation with PHA and Anti-CD3/Anti-CD28 Coated Beads.

A decrease in T cell count or reduced T cell function can be indicative of T cell immunodeficiency. In the present study, T-cell function was assessed using Carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution test after stimulation with commonly used Phytohaemagglutinin (PHA) or anti-CD3/anti-CD28 coated beads in pediatric patients with recurrent infections. Seven infants with recurrent infections and seven sex/age-matched healthy infants were included in this study. A blood cell count, immunophenotyping, and serum immunoglobulin level were performed. The proliferation of T cells was also assessed with CFSE dilution after stimulation with PHA or anti-CD3/anti-CD28 coated beads.  This study showed increased IgA, IgG, and IgM levels in patients compared to the controls. In contrast to the controls, the immunophenotyping results showed a significant decline in the number of CD4+ T cells in patients. Although there was no difference in CD3+ T cell proliferation between patients and controls, the CD4+ and CD8+ T cell proliferation rates were significantly decreased in patients when stimulated with PHA. As a mitogen with the potential for maximum proliferation of T cells, PHA is better able to distinguish between patients with recurrent infections and controls than anti-CD3/anti-CD28, which mimics only the TCR pathway for stimulation of T cells.

COVID-19 in Chronic Granulomatosis Disease: A Case Report.

A novel coronavirus disease known as Coronavirus Disease 2019 (COVID-19) has spread quickly throughout the world, and it was declared a pandemic in March 2022. Chronic granulomatous disease (CGD) is a diverse group of genetic disorders characterized by recurrent bacterial and fungal infections, resulting in granulomas due to the inability of phagocytes to destroy microbes. Even though it is thought that impaired neutrophil activity is a protective mechanism against severe COVID-19-induced cytokine storms and hyper-inflammatory responses, patients with CGD have normal immunity to most viruses. Here, we present two CGD patients who were hospitalized due to severe COVID-19 infections, which suggests that COVID-19 might have a different pathogenesis than other viruses.

Homozygous Autosomal Recessive DIAPH1 Mutation Associated with Central Nervous System Involvement and Aspergillosis: A Rare Case.

The DIAPH1 gene fulfills critical immune and neurodevelopmental roles. It encodes the mammalian Diaphanous-related formin (mDia1) protein, which acts downstream of Rho GTPases to promote F-actin polymerization and stabilize microtubules. During mitosis, this protein is expressed in human neuronal precursor cells and considerably affects spindle formation and cell division. In humans, dominant gain-of-function DIAPH1 variants cause sensorineural deafness and macrothrombocytopenia (DFNA1), while homozygous DIAPH1 loss leads to seizures, cortical blindness, and microcephaly syndrome (SCBMS). To date, only 16 patients with SCBMS have been reported, none of whom were from Iran. Furthermore, aspergillosis is yet to be reported in patients with homozygous DIAPH1 loss, and the link between SCBMS and immunodeficiency remains elusive. In this study, we shed further light on this matter by reporting the clinical, genetic, and phenotypic characteristics of an Iranian boy with a long history of recurrent infections, diagnosed with SCBMS and immunodeficiency (NM_005219.5 c.3145C > T; p.R1049X variant) following aspergillosis and SARS-CoV-2 coinfection.

An Update on Protective Effectiveness of Immune Responses After Recovery From COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits variable immunity responses among hosts based on symptom severity. Whether immunity in recovered individuals is effective for avoiding reinfection is poorly understood. Determination of immune memory status against SARS-CoV-2 helps identify reinfection risk and vaccine efficacy. Hence, after recovery from COVID-19, evaluation of protective effectiveness and durable immunity of prior disease could be significant. Recent reports described the dynamics of SARS-CoV-2 -specific humoral and cellular responses for more than six months in convalescent SARS-CoV-2 individuals. Given the current evidence, NK cell subpopulations, especially the memory-like NK cell subset, indicate a significant role in determining COVID-19 severity. Still, the information on the long-term NK cell immunity conferred by SARS-CoV-2 infection is scant. The evidence from vaccine clinical trials and observational studies indicates that hybrid natural/vaccine immunity to SARS-CoV-2 seems to be notably potent protection. We suggested the combination of plasma therapy from recovered donors and vaccination could be effective. This focused review aims to update the current information regarding immune correlates of COVID-19 recovery to understand better the probability of reinfection in COVID-19 infected cases that may serve as guides for ongoing vaccine strategy improvement.

Geoclimatic risk factors for childhood asthma hospitalization in southwest of Iran.

BACKGROUND: Asthma is a chronic respiratory disease resulting from a complex interaction between genetic and environmental factors. Among environmental factors, climatic and geographical variations have an important role in increasing asthma hospitalization. The current study aimed to investigate the effect of geoclimatic factors on the occurrence of childhood asthma hospitalization in Fars province, southwest Iran. METHOD: We mapped the addresses of 211 hospitalized patients with childhood asthma (2016-2019) and investigated the effects of different temperature models, mean annual rainfall and humidity, number of frosty and rainy days, evaporation, slope, and land covers on the occurrence of childhood asthma hospitalization using a geographical information system. The Kriging and Spline methods have been used for generating interpolated models. Data were analyzed using logistic regression. RESULTS: In the multivariate model, urban setting was recognized as the most important childhood asthma hospitalization predictor (p < 0.001, odds ration [OR] = 35.044, confidence interval [CI] = 9.096-135.018). The slope was considered the determinant of childhood asthma hospitalization when analyzed independently and its increase was associated with decreased childhood asthma hospitalization (p = 0.01, OR = 0.914, CI = 0.849-0.984). CONCLUSION: In the current study, the urban setting was the most important risk factor associated with increased childhood asthma hospitalization.

Identification of the Most Common Allergens of Acer velutinum Pollen.

Pollens have been identified as potent inducers of allergic diseases worldwide. Acer velutinum (Persian maple) tree is an important source of allergic pollens in Iran. This study aimed to identify the immunoglobulin E (IgE)-reactive components of A. velutinum pollen extract in patients with maple allergy. We aimed to evaluate its allergenic components; using IgE in the serum of patients with maple allergy. Twenty-two patients with a clinical history of reaction and a positive skin-prick test to maple pollen extract were included in this study. Identification of IgE-binding proteins in A. velutinum pollen extract was performed by immunoblotting using sera from sensitive patients. A protein band with a molecular weight of around 70 kDa was the most IgE-reactive allergen in A. velutinum pollen extract detected by this method. Identification of a protein with a molecular weight of about 70kDa, as the most reactive allergen of A. velutinum pollen extract, can be considered as a potential allergen for designing diagnostic kits or as a target for immunotherapy of allergic patients with maple allergy.

Investigating the association of atopy and aeroallergen sensitization and chronic spontaneous urticaria.

Introduction: Chronic spontaneous urticaria (CSU) is a common skin allergic reaction with an unknown mechanism. There is inadequate evidence to support the role of aeroallergen sensitization in CSU. Aim: The present study was conducted to investigate the association between the aeroallergen sensitivity and CSU. Material and methods: In this cross-sectional study, 91 patients with CSU were recruited. Information on demographic characteristics was collected. The skin prick test (SPT) for most prevalent aeroallergens and pulmonary function test (PFT) were performed and the results were clinically matched to investigate the allergic rhinitis (AR) and asthma. Total serum immunoglobulin E (IgE) concentration was analysed in the subjects for the presence of atopy. Results: Ninety one patients (75 of them were females) were enrolled in the study (with a mean age of 36.90 ±12.93 years). SPT result was positive in 75 (82.4%) subjects. Weeds (67 cases, 73.6%), trees (61 cases, 67%), and dust mites (55 cases, 60.4%) were the most common pollens in the positive SPT samples. Thirty-seven (40.7%) of the patients had allergic rhinitis. There was a statistically significant association between the presence of AR and positive SPT result (p = 0.002). Eight patients had allergic asthma and 45 (49.4%) of the patients had a total serum IgE level of more than 100 IU/ml. Conclusions: Our results indicated a clear association between the presence of aeroallergen sensitivity and development of CSU. AR exists as a co-morbidity of CSU.

A Comparative Study of Montelukast and Azelastine add on Therapy in Moderate to Severe Allergic Rhinitis Treatment: A Double-Blind Randomized Clinical Trial.

BACKGROUND: Allergic Rhinitis (AR) is a prevalent chronic inflammatory nasal condition with significant negative effects on the patients' quality of life. This study aimed to investigate the efficacy of Montelukast and intranasal antihistamine in combination with intranasal corticosteroid (INCS) in moderate to severe allergic rhinitis on the patients' quality of life and AR control. METHOD: This double-blind randomized clinical trial study was carried out on 66 moderate to severe AR patients referred to Namazi Hospital, Shiraz, Iran from 2020 to 2021, who were randomly divided into 3 groups. Group one received Montelukast add-on therapy and Budesonide nasal spray. The second group received intranasal antihistamine (Azelastine) add-on therapy and Budesonide nasal spray and the third group as the control group received intranasal Budesonide spray with a placebo tablet.To measure the impact of each medication on the patient's quality of life and AR control, we employed the Sino-Nasal Outcome Test-22 questionnaire (SNOT 22). We evaluated the symptoms and compared them at baseline, one and three months after the start of treatments. Spirometry was performed to investigate the possibility of co-morbid asthma at baseline and end of the study. RESULTS: The patients' mean age was 30.13 ± 12.7 years. Most patients experienced perennial AR (65.2%). Reduction of mean scores SNOT22 was statistically different between groups (P-value < 0.001). Three months after treatment, the mean decrease of SNOT-22 in the Azelastine group was statistically significant compared to both Montelukast (P-value < 0.001) and control groups (P-value < 0.001). No significant difference was observed between the Montelukast and control groups (P-value = 0.142). 23 of 66 patients were diagnosed with asthma and asthma treatment was initiated. The amount of FEV1 change after AR treatment was not statistically significant between the groups in asthmatic patients (P-value = 0.351). CONCLUSION: Based on our findings, we recommend Azelastine in conjunction with an intranasal corticosteroid for the treatment of moderate to severe allergic rhinitis. In moderate to severe AR or even asthma management, Montelukast has no greater impact than INCS.

The Effect of COVID-19 Pandemic on Patients with Primary Immunodeficiency: A Cohort Study.

Both adaptive and innate immune responses are essential for an effective defense against the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection. We aimed to investigate the effect of the coronavirus disease 2019 (COVID-19) pandemic on patients with primary immunodeficiency (PID). This study was performed on patients who were diagnosed with PID by immunologist specialists and referred to Imam Reza Clinic of Asthma and Allergy, affiliated with Shiraz University of Medical Sciences, (Shiraz, Iran) for regular check-ups. The patients were enrolled in this cohort study and followed for any sign of COVID-19 from March 2020 to May 2021. COVID-19 infection was confirmed using a real-time polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. Among the 90 PID patients under study, nine patients (10%) were diagnosed positive for COVID-19 infection. Five out of these nine patients belonged to the combined immunodeficiency (CID) category, while four patients were categorized as having primary antibody deficiencies (PADs). Eight patients with COVID-19 were required to be admitted to the hospital, and three patients died after hospitalization due to COVID-19 infection. It seems that patients with CID are at a higher risk of mortality, due to COVID-19 infection, that other types of PID.

Assessing the Association of Kawasaki Disease Symptoms and Echocardiographic Findings.

Kawasaki disease is an acute systemic vasculitis which can cause cardiac involvement among other symptoms. In this study we aimed to assess the relationship between the echocardiographic findings of Kawasaki disease with the clinical and paraclinical findings of the patients. In this cross-sectional study, the symptoms of 307 Kawasaki patients were registered and the association of the symptoms with paraclinical findings and echocardiographic studies was assessed. 190 (61.9%) of the patients were male and 117 (38.1%) were female. 193 patients (62.9%) did not have any abnormalities in their echocardiography, while others showed coronary artery aneurysms, perivascular brightness, coronary artery dilatation, and trivial Mitral Regurgitation in their echocardiography. A significant inverse relationship was seen with echocardiographic findings and age. Thrombocytosis, conjunctivitis, and oral and/or pharyngeal erythema and/or strawberry tongue were associated with higher rates of echocardiographic abnormalities. Echocardiographic abnormalities are associated with younger age, higher platelets, and the existence of conjunctivitis and oral and/or pharyngeal erythema and/or strawberry tongue.

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.