Clinical heterogeneity in families with multiple cases of inborn errors of immunity.

BACKGROUND: Inborn errors of immunity (IEI) are a diverse range of genetic immune system illnesses affecting the innate and/or adaptive immune systems. Variable expressivity and incomplete penetrance have been reported in IEI patients with similar clinical diagnoses or even the same genetic mutation. METHODS: Among all recorded patients in the national IEI registry, 193 families with multiple cases have been recognized. Clinical, laboratory and genetic variability were compared between 451 patients with different IEI entities. RESULTS: The diagnosis of the first children led to the earlier diagnosis, lower diagnostic delay, timely treatment and improved survival in the second children in the majority of IEI. The highest discordance in familial lymphoproliferation, autoimmunity and malignancy were respectively observed in STK4 deficiency, DNMT3B deficiency and ATM deficiency. Regarding immunological heterogeneity within a unique family with multiple cases of IEI, the highest discordance in CD3+, CD4+, CD19+, IgM and IgA levels was observed in syndromic combined immunodeficiencies (CID), while non-syndromic CID particularly severe combined immunodeficiency (SCID) manifested the highest discordance in IgG levels. Identification of the first ATM-deficient patient can lead to improved care and better survival in the next IEI children from the same family. CONCLUSION: Intrafamilial heterogeneity in immunological and/or clinical features could be observed in families with multiple cases of IEI indicating the indisputable role of appropriate treatment and preventive environmental factors besides specific gene mutations in the variable observed penetrance or expressivity of the disease. This also emphasizes the importance of implementing genetic evaluation in all members of a family with a history of IEI even if there is no suspicion of an underlying IEI as other factors besides the underlying genetic defects might cause a milder phenotype or delay in presentation of clinical features. Thus, affected patients could be timely diagnosed and treated, and their quality of life and survival would improve.

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.

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.

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.

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.

Airborne Pollens and Their Association with Meteorological Parameters in the Atmosphere of Shiraz, Southwest Iran.

Airborne pollen is considered one of the causative agents of hay fever, allergic rhinitis, conjunctivitis, and asthma. We aimed to investigate airborne pollens in the context of Shiraz located in the southwest of Iran and find their association with meteorological parameters.  The survey was conducted from October 2017 to September 2018, using seven days of volumetric Burkard spore trap, located in the center of the city. A total of 5810 pollen grains/m3 belonging to 15 taxa were identified and recorded. Among them, 73.8% was the tree, while the grass, shrub, and weed constituted 13.56%, 3.5%, and 9.2% of total reported pollens, respectively. The major pollen types were Platanaceae (28.39%), Oleaceae (21.17%), Pinaceae (15.11%), Amaranthaceae (9.29%), and Brassicaceae (8.02%). A higher number of pollen counts and types were recorded in March, followed by September, while it was lower in May. Meteorological parameters were correlated with the monthly pollen counts. Wind speed was found to have a positive correlation with Platanaceae concentration. The significant correlation between pollen concentration and the temperature was positive for Poaceae, Amaranthaceae, and Plantaginaceae and negative for Rosaceae, Oleaceae, and Ulmaceae.  Poaceae and Amaranthaceae were negatively correlated with humidity and positively with Rosaceae, Oleaceae, and Plantaginaceae. A negative correlation was found between rainfall and Poaceae and Amaranthaceae, while Plantaginaceae had a positive correlation with this parameter. The results of this study may be helpful for allergologists in the diagnosis and treatment of airborne allergic disorders due to pollen grains.

Molecular Cloning and Expression of a New Allergen of Acacia farnesiana (Aca f 2).

Inhalation of pollens from different species of Acacia is a common cause of respiratory allergy in tropical areas of the world. Acacia farnesiana is commonly used as street trees in towns and ornamental shade trees in parks and gardens throughout arid and semi-arid regions of Asia. This study aimed to produce and purify the A. farnesiana pollen profilin (Aca f 2) and evaluate its nucleotide sequence homology with profilins of common allergenic plants to predict allergenic cross-reactivity. Thirty-nine patients who were allergic to Acacia pollens were included in the study. Cloning of Acacia profilin-coding sequence was performed by polymerase chain reaction using primers from Acacia pollen RNA. The cDNA of Acacia pollen profilin was then expressed in Escherichia coli using pET-21b(+) vector and purified by metal affinity chromatography. Immunoreactivity of the recombinant Acacia profilin (rAca f 2) was evaluated by specific ELISA, immunoblotting, and inhibition assays. The coding sequence of the Acacia profilin cDNA was recognized as a 399-bp open reading frame encoding 133 amino acid residues. Eighteen patients (18/39, 46.15%) had significant specific IgE levels against Aca f 2. Immunodetection and inhibition assays indicated that purified Aca f 2 might be the same as that in the crude extract. Aca f2, the first allergen from A. farnesiana pollen, was identified as belonging to the family of profilins. The amino acid sequence homology analysis showed high cross-reactivity between Aca f 2 and other profilins from botanically unrelated common allergenic plants.

Pro j 2 is mesquite profilin: molecular characteristics and specific IgE binding activity.

BACKGROUND: Pollens from mesquite (Prosopis juliflora) are potent allergen responsible in causing immediate hypersensitivity reactions in susceptible people in tropical countries. OBJECTIVE: This study aimed to clone, express and purify the mesquite pollen profilin (Pro j 2) as well as evaluating its nucleotide sequence homology in order to predict allergenic cross-reactivity with profilins of common allergenic plants. METHODS: Immunoblotting assay and specific ELISA were applied to determine the immunoreactivity of sera from 35 patients who were allergic to mesquite pollen. The mesquite profilin-coding sequence was cloned into PTZ57R/T vector and amplified. The cDNA of mesquite pollen profilin was then expressed in Escherichia coli using pET-21b (+) vector and puri?ed by one-step Ni2+ a?nity chromatography. IgE binding capacity of the recombinant mesquite profiling (rPro j 2) was analyzed by specific ELISA, immunoblotting, and inhibition assays. RESULTS: cDNA nucleotide sequencing revealed an open reading frame of 399bp encoding for 133 amino acids which belongs to the profilin family. Seventeen patients (17/35, 48.57%) had significant specific IgE level for rPro j 2. Immunodetection and inhibition assays indicated that puri?ed rPro j 2 might be similar as that in the crude extract. CONCLUSION: Pro j 2, as a new allergen from mesquite pollen, was produced in E. coli with an IgE-reactivity similar to that of its natural counterpart. The amino acid sequences homology analysis of mesquite profilin and several profilin molecules from other plants showed high degree of cross-reactivity among plant-derived profilins from unrelated families.

Immunochemical characterization of prosopis juliflora pollen allergens and evaluation of cross-reactivity pattern with the most allergenic pollens in tropical areas.

Allergy to Prosopis juliflora (mesquite) pollen is one of the common causes of respiratory allergy in tropical countries. Mesquite is widely used as street trees in towns and ornamental shade trees in parks and gardens throughout arid and semiarid regions of Iran. The inhalation of mesquite pollen and several species of Amaranthus/Chenopodiaceae family is the most important cause of allergic respiratory symptoms in Khuzestan province. This study was designed to evaluate IgE banding proteins of mesquite pollen extract and its IgE cross-reactivity with other allergenic plants. Twenty patients with allergic symptoms and positive skin prick tests (SPT) for mesquite pollen extract participated in the study. Crude pollen extract was prepared from local mesquite trees and used for the evaluation of allergenic profiles of P. juliflora pollen extract by Sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and IgE-immunoblotting. There were several protein bands in mesquite pollen extract using SDS-PAGE with the approximate range of molecular weight of 10-85 kDa. The most frequent IgE reactive bands among the patients' sera were approximately 20 and 66 kDa. However, there were other IgE reactive protein bands among the patients' sera with molecular weights of 10, 15, 35, 45, 55 and 85 kDa. Inhibition experiments revealed high IgE cross-reactivity between mesquite and acacia. There are several IgE-binding proteins in P. juliflora pollen extract. Results of this study indicate that proteins with a molecular weight of 10 to 85 kDa are the major allergens in P. juliflora pollen extract.