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Background: Severe Acute Respiratory Syndrome Coronavirus 2 has affected millions of people, and especially in adult patients with underlying diseases lead to death. Meanwhile pediatric patients with inherited defects of T cell should be prone to viral diseases. Case Presentation: Herein, we report an infant with severe combined immunodeficiencies, who were affected and died because of COVID-19. Conclusion: Considering the importance of finding how immune system can affect the viral infection, presentation of COVID-19 in immune deficient patients can be valuable.

BACKGROUND Celiac disease is a non-IgE mediated food allergy, which can cause extensive villus atrophy. Because of increased food allergen absorption, there are elevated IgA and IgG antibodies in these patients, so there is a concern about IgE antibody production against wheat and other cereals. METHODS In this study, we evaluated IgE-mediated hypersensitivity to wheat, rice, and other cereals in children with celiac disease. RESULTS 22 patients (50%) had at least one positive skin prick test to food allergens. The most frequent food allergen was peanut (31.8%), followed by wheat (18.2%), corn (9.1%), and rice (4.5%). The results revealed no significant correlation between age, sex, and the results of the skin prick test (p >0.05). The correlation between diagnosis time of celiac disease and results of skin prick test was also not significant statistically (p >0.05). CONCLUSION Because of the high prevalence of IgE mediated hypersensitivity to cereals and beans in children with celiac disease, a skin prick test might be considered in these patients, especially in refractory cases.

BACKGROUND: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunological, and molecular data of monogenic IEI patients with and without autoimmune manifestations. METHODS: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data. RESULTS: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1) were born to consanguineous parents. At the time of the study, 330 individuals (75.7) were alive and 106 (24.3) were deceased. Autoimmunity was reported in 92 (20.0) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0), ATM (in 13 patients, 14.0), and BTK (in 9 patients, 10.0) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100), 3 of 3 AIRE (100), 21 of 30 LRBA (70.0) mutated genes had the highest prevalence of autoimmunity. CONCLUSIONS: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next generation sequencing (due to phenocopies of IEI genes) to discover responsible genes for the immune dysregulation at an early stage of the disease.

Although presentation of COVID‐19 in patients with immunodeficiency could be mild, it should not be missed, while early diagnosis and appropriate treatment can survive infected patients. Because even severe infections in PID patients may be presented with few symptoms and signs, this diagnosis should be considered in those immunocompromised patients who have exacerbating preexisting symptoms.

Chronic urticaria (CU) affects about 1% of the world population of all ages, mostly young and middle-aged women. It usually lasts for several years (> 1 year in 25-75% of patients) and often takes > 1 year before effective management is implemented. It presents as chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU) or both in the same person. More than 25% of cases are resistant to H1 -antihistamines, even at higher doses, and third- and fourth-line therapies (omalizumab and ciclosporin) control the disease only in two-thirds of H1 -antihistamine-resistant patients. Here we review the impact of CU on different aspects of patients' quality of life and the burden of this chronic disease for the patient and society. CU may have a strong impact on health-related quality of life (HRQoL), particularly when CSU is associated with angio-oedema and/or CIndU (Dermatology Life Quality Index > 10 in 30% of patients). Comorbidities, such as anxiety and depression, which are present in more than 30% of patients with CSU, compound HRQoL impairment. Severe pruritus and the unpredictable occurrence of weals and angio-oedema are responsible for sleep disorders; sexual dysfunction; limitations on daily life, work and sports activities; interfering with life within the family and in society; and patients' performance at school and work (6% absenteeism and 25% presenteeism). Apart from treatment costs, with annual values between 900 and 2400 purchasing power parity dollars (PPP$) in Europe and the USA, CU is associated with a high consumption of medical resources and other indirect costs, which may reach a total annual cost of PPP$ 15 550.

Introduction: Chronic urticaria (CU) is a common disease that primarily affects females. Although commonly encountered, there is little data on how pregnancy interact with CU. We analysed treatment use by CU patients before, during and after pregnancy as well as outcomes of pregnancy. Material and Methods: PREG-CU was a prospective and retrospective, international, multicentre, study of the Urticaria Centers of Reference and Excellence (UCARE) network. Data were collected via a 47-item-questionnaire completed by CU patients who became pregnant during their disease course. Results: Questionnaires from 288 CU patients from 13 countries were analysed. During pregnancy, most patients (60%) used urticaria medication (standard dose second generation H1-antihistamines [SD-sgAH] (35.1%), first generation H1-antihistamines (7.6%), high-dose sgAH (5.6%), and omalizumab (5.6%). The preterm birth rate was 10.2%, and preterm rates of patients who did and did not receive treatment during pregnancy were similar (11.6% vs 8.7%). Emergency referrals for CU and twin birth were risk factors for preterm birth. The caesarean delivery rate was 51.3%. More than 90% of new-borns. were healthy at birth. There was no link between any patient or disease characteristics or treatments and medical problems at birth. Eight of 10 (78.8%) women with CU breastfed their babies and most (54.3%) used urticaria medication while breastfeeding. Conclusion: Rates of preterm births and medical problems of new-borns in patients with CU were similar to population norms and not linked to treatment used during pregnancy. Emergency referrals increase risk of preterm birth and emphasizes the importance of urticaria control during pregnancy.

Background: Considering the psychobiological aspects of various dermatological diseases and the role of personality traits in the development of chronic skin diseases such as chronic urticaria, the present study aimed to assess the personality traits of patients with chronic spontaneous urticaria (CSU) compared to healthy individuals. Methods: In this cross-sectional study during 2016 - 2018, all patients with CSU who referred to Immunology and Allergy Clinic of Ghaem hospital, the Center of reference and excellence in urticaria (UCARE), considered as research community; 100 patients with CSU were selected using the convenience sampling method. Moreover, 100 healthy participants were selected as the control group. Research instruments were Temperament and Character Inventory (TCI) and a demographic checklist. Data were analyzed using descriptive statistics, t-test, and chi-square test using SPSS Software version 23. Results: The patients had higher scores in novelty-seeking (P = 0.041) and harm avoidance (P = 0.015), while the healthy individuals had higher scores in self-directedness (P = 0.003) and cooperativeness (P = 0.001). Moreover, male patients had higher scores in novelty-seeking (P = 0.006) and reward dependence (P = 0.013); however, female patients had higher scores in self-transcendence (P = 0.001) and cooperativeness (P = 0.019). Furthermore, there was a correlation between the disease duration of with reward dependence, self-directedness, and self-transcendence. Conclusions: Personality traits seem to be associated with CSU. In this regard, patients with CSU had higher scores in novelty-seeking and harm avoidance and lower scores in self-directedness and cooperativeness than healthy individuals.

Background and Objective: Chronic spontaneous urticaria (CSU) is a distressing disease. We report real-world data from the global Chronic Urticaria Registry (CURE) about associations between various CSU states and sleep impairment, plus important health-related quality-of-life (HRQoL) outcomes and compared different methods to assess CSU states. Methods: CURE data were collected at baseline and 6-monthly follow-ups (FU). Assessments included CSU states using the Urticaria Control Test (UCT), weekly Urticaria Activity Score (UAS7), and Physician Global Assessment (PhyGA) of treatment response. Complete response to treatment (CR, UAS7 = 0), complete control of disease (CC, UCT = 16), and PhyGA = CR were assessed, plus the Dermatology Life Quality Index and the Chronic Urticaria Quality-of-Life Questionnaire (CU-Q2oL) sleep domain. Results: Overall, 2078 patients were included. At baseline, 9.8%, 17.9%, and 42.3% of patients had UCT = 16, UAS7 = 0, or PhyGA = CR, respectively, which increased at FU1 and FU2. Patients with higher UCT scores had better sleep and HRQoL. The presence of angioedema without wheals, episodic disease, omalizumab treatment, and male sex were associated with CC (P

Background: cold urticaria (ColdU), that is, the occurrence of wheals or angioedema in response to cold exposure, is classified into typical and atypical forms. The diagnosis of typical ColdU relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold-induced anaphylaxis (ColdA). We aimed to determine risk factors for ColdA in typical ColdU. Methods: an international, cross-sectional study COLD-CE was carried out at 32 urticaria centers of reference and excellence (UCAREs). Detailed history was taken and CST with an ice cube and/or TempTest(R) performed. ColdA was defined as an acute cold-induced involvement of the skin and/or visible mucosal tissue and at least one of: cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms. Results: of 551 ColdU patients, 75% (n = 412) had a positive CST and ColdA occurred in 37% (n = 151) of the latter. Cold-induced generalized wheals, angioedema, acral swelling, oropharyngeal/laryngeal symptoms, and itch of earlobes were identified as signs/symptoms of severe disease. ColdA was most commonly provoked by complete cold water immersion and ColdA caused by cold air was more common in countries with a warmer climate. Ten percent (n = 40) of typical ColdU patients had a concomitant chronic spontaneous urticaria (CSU). They had a lower frequency of ColdA than those without CSU (4% vs. 39%, p = .003). We identified the following risk factors for cardiovascular manifestations: previous systemic reaction to a Hymenoptera sting, angioedema, oropharyngeal/laryngeal symptoms, and itchy earlobes. Conclusion: coldA is common in typical ColdU. High-risk patients require education about their condition and how to use an adrenaline autoinjector., GA(2)LEN UCARE Network

Studies have indicated a possible role for serotonin transporter protein (SERT) in the pathophysiology of inflammatory skin disorders. This study was aimed to determine the expression of SERT in the skin of patients with chronic spontaneous urticaria (CSU) and its relation to depression and anxiety. In this case–control study, 30 CSU patients and 30 healthy controls were evaluated with skin biopsies to evaluate the expression of the SERT protein based on histopathologic findings. Beck depression and anxiety inventories were used to investigate depression and anxiety in the case group. Data were analyzed by SPSS software. P values

Introduction: The relationship between allergic and autoimmune diseases is an important issue, which has recently attracted the researchers’ interest. Aim: To determine the relationship between atopy and psoriasis. Material and methods: This case-control study was conducted on 102 patients referred to the Ghaem Hospital, Mashhad, Iran, in 2016. The participants were assigned into two groups: experimental and control groups, including the patients suffering from psoriasis and those with no history of cutaneous or other systemic diseases, respectively. Both groups filled in the ISAAC questionnaire and had skin prick tests. In addition, the serum levels of immunoglobulin E (IgE) and blood eosinophil cell count were measured. The data were analysed using the regression test through SPSS version 16. Results: According to the results of the ISAAC questionnaire, there was a significant difference between the control and experimental groups in terms of asthma (p = 0.04). The mean serum concentrations of IgE and eosinophil cell count were not significantly different between the experimental (153.93 IU/ml and 187.77 cells/μl, respectively) and control groups (152.19 IU/ml and 187.68 cells/μl, respectively) (p = 0.057 and p = 0.886, respectively). In addition, there was an indirect correlation between the eosinophil cell count and psoriasis severity (p = 0.032, r = –0.297). Furthermore, the comparison of the skin prick test results revealed no significant difference between the two groups regarding the number of positive and negative cases (p = 0.436). Conclusions: The findings suggested that atopy was not common in the patients with psoriasis and supported the concept that atopy protects against such autoimmune diseases such as psoriasis. © 2019 Termedia Publishing House Ltd. All rights reserved.

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) (P0.001). 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.

BackgroundAtopic dermatitis (AD) is a chronic, inflammatory, and severely Pruritus cutaneous disease that has an immunologic base. The most common treatments are topical steroids, which bring many adverse side effects. Vitamin D can adjust the immune system; therefore, in this study, we investigated the effect of vitamin D on the abundance of Treg cells in AD patients. MethodsIn this interventional study, 40 subjects who completed the intervention were enrolled, including 20 AD patients (as the experimental group) and 20 healthy subjects (as the control group). Accordingly, the subjects whose vitamin D levels was less than 30 ng/ml were assigned to receive vitamin D (1000 IU) daily for a 2-month duration. The severity of AD was evaluated based on SCORAD (Scoring Atopic Dermatitis) and the amount of CD4+CD25+Foxp3+Treg cells was also assessed using Flow cytometry. ResultsAverage serum level of vitamin D before performing the treatment in the experimental (14/90±4/5) and control groups (15/95±5/0) was lower than that of after the treatment (experimental group 24/60±5/2 and control group 23/60±7/3) (PTrial registration: IRCT20150716023235N13, Registered 11 Feb 2018, https://www.irct.ir

*Ateş, Can ( Aksaray, Yazar ), SciVal Topics Funding details Abstract Background: Chronic urticaria (CU) predominantly affects women, and sex hormones can modulate disease activity in female CU patients. As of now, the impact of pregnancy on CU is largely unknown. Aim: To analyze the course and features of CU during and after pregnancy. Patients and methods: PREG-CU is an international, multicenter study of the Urticaria Centers of Reference and Excellence (UCARE) network. Data were collected via a 47-item questionnaire completed by CU patients, who became pregnant within the last 3 years. Results: A total of 288 pregnancies of 288 CU patients from 13 countries were analyzed (mean age at pregnancy: 32.1 ± 6.1 years, duration of CU: 84.9 ± 74.5 months; CSU 66.9%, CSU + CIndU 20.3%, CIndU 12.8%).During pregnancy, 51.1% of patients rated their CU as improved, 28.9% as worse, and 20.0% as unchanged.CU exacerbations most commonly occurred exclusively during the third trimester (in 34 of 124 patients; 27.6%) or the first (28 of 124; 22.8%). The risk factors for worsening of CU during pregnancy were having mild disease and no angioedema before pregnancy, not taking treatment before pregnancy, CIndU, CU worsening during a previous pregnancy, treatment during pregnancy, and stress as a driver of exacerbations. After giving birth, urticaria disease activity remained unchanged in 43.8% of CU patients, whereas 37.4% and 18.1% experienced worsening and improvement, respectively. Conclusions: These results demonstrate the complex impact of pregnancy on the course of CU and help to better counsel patients who want to become pregnant and to manage CU during pregnancy.

BackgroundAllergen-specific immunotherapy is known as the only disease-modifying treatment for IgE-mediated allergic disorders. Intra lymphatic immunotherapy (ILIT) is a safe, effective, and time-saving alternative to subcutaneous immunotherapy (SCIT). This study aimed to evaluate the effects and safety of ILIT in patients with moderate to severe allergic rhinitis. MethodsIn this clinical trial, fifteen patients with moderate to severe allergic rhinitis between 18-65 years old received monthly intralymphatic inguinal injections of an active allergen (1000 SQ-U Salsola kali pollen). Clinical effects were assessed before and 4 weeks after treatment and at two consecutive pollination seasons and following non-pollination season in April.ResultsNo moderate or severe reactions were recorded following the ILIT treatment. Lymph node enlargement, local itching/erythema were seen in 6.7%, 13.3% of total respectively one day after injection. Patients who received ILIT experienced a significant clinical improvement in self-recorded seasonal allergic symptoms after treatment, as compared to themselves before ILIT. Quality of life significantly got better based on the Mini RQLQ questionnaire.ConclusionAlthough this study is based on a limited number of patients, ILIT with Salsola-pollen extract appears to decrease symptoms of allergic rhinitis without causing any crucial complications.This clinical trial study was recorded in the Iran Registry of Clinical Trials (IRCT20161206031256N2).

Brain tumors are the rarest cause of cerebrospinal fluid rhinorrhea. Non-traumatic cerebrospinal fluid rhinorrhea is also a relatively rare condition. It may be misdiagnosed as allergic rhinitis or chronic sinusitis and lead to unsuitable treatment. We described a 34-yearold man who came to our allergy clinic with a chief complaint of clear rhinorrhea from his left nostril with more than four years of duration. Only hypertrophy of left inferior concha was found in the clinical examination. His rhinorrhea aggravated when bending forward. So we were suspicious of CSF rhinorrhea.MRI was done for him and demonstrated a large tumor in the pineal region. The patient underwent surgery with resection of the mass via an infratentorial-supracerebellar approach. This case showed the role of maintaining differential diagnosis for a common complaint; rhinitis which is seen as usual.

Background. In the recent coronavirus disease 2019 (COVID-19) pandemic, millions of people have been affected so far. Clinical manifestations and natural history of infections have a very wide range, which is important to know it in various underlying diseases. Although children are less affected than adults, its presentation especially in those with underlying diseases should not be neglected.Case presentation. Herein we report the first case of specific antibody deficiency, who was affected with COVID-19. The patient suffered from rhinorrhea and modestly increased in productive cough, but real-time reverse transcription polymerase chain reaction was positive for COVID-19.Conclusions. Although presentation of COVID-19 in patients with immunodeficiency could be mild, it should not be missed, while early diagnosis and appropriate treatment can survive affected patients.

Background: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. Methods: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children’s Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. Results: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. Conclusion: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity.

The number of inherited diseases and the spectrum of clinical manifestations of primary immunodeficiency disorders (PIDs) are ever-expanding. Molecular diagnosis using genomic approaches should be performed for all PID patients since it provides a resource to improve the management and to estimate the prognosis of patients with these rare immune disorders. The current update of Iranian PID registry (IPIDR) contains the clinical phenotype of newly registered patients during last 5 years (2013–2018) and the result of molecular diagnosis in patients enrolled for targeted and next-generation sequencing. Considering the newly diagnosed patients (n = 1395), the total number of registered PID patients reached 3056 (1852 male and 1204 female) from 31 medical centers. The predominantly antibody deficiency was the most common subcategory of PID (29.5%). The putative causative genetic defect was identified in 1014 patients (33.1%) and an autosomal recessive pattern was found in 79.3% of these patients. Among the genetically different categories of PID patients, the diagnostic rate was highest in defects in immune dysregulation and lowest in predominantly antibody deficiencies and mutations in the MEFV gene were the most frequent genetic disorder in our cohort. During a 20-year registration of Iranian PID patients, significant changes have been observed by increasing the awareness of the medical community, national PID network establishment, improving therapeutic facilities, and recently by inclusion of the molecular diagnosis. The current collective study of PID phenotypes and genotypes provides a major source for ethnic surveillance, newborn screening, and genetic consultation for prenatal and preimplantation genetic diagnosis.

BACKGROUND: Asthma is the most prevalent chronic disease in the pediatric age group. The disease affects different aspects of the children's lives, such as physical, emotional, social and educational aspects. Thus, more focus has been on the quality of life in these patients rather than the duration of their illness in recent years.AIM: This study examined the different aspects of quality of life in asthmatic children for the first time in this geographic area.METHODS: The study was cross-sectional conducted in 2015-2016. The asthmatic group was 100 patients aged 8 to 12 admitted to the Asthma and Allergy Clinic of Ghaem Hospital (as) in Mashhad with the control group composed of 100 healthy children of the same age and gender. The standard questionnaire pedsQLTM was used for comparing the quality of life of children in the two groups. Statistical analysis was SPSS23 with P-value less than 0.05, which was statistically significant.RESULTS: In each group, 58 patients were boys, and 42 were girls. In a comparison of the quality of life of children, the asthma group with a mean total score of Peds QL 20.99 ± 12.54 compared to the healthy children with a mean total score of Peds QL of 8.8 ± 5.41 had a lower quality of life (P < 0.001). Moreover, regarding various aspects of quality of life asthma group had a lower quality of life in physical performance, emotional performance and performance in school (P < 0.001). Nonetheless, there was no significant difference between the two groups considering social function (P = 0.267). Examining the relationship between Peds QL score of patients with asthma with various variables was indicative of the fact that Peds QL scores were significantly correlated with the gender of the patients, showing better quality of life in the girls (P = 0.001).CONCLUSION: The results indicated that children with asthma have a significantly lower quality of life compared with healthy children of the same age. Also, in examining the different aspects of quality of life, these children had a lower quality of life in physical performance, emotional performance, and performance at school, and were at the level as that of healthy children only in social performance.

Background Combined immunodeficiencies (CIDs) are diseases of defective adaptive immunity with diverse clinical phenotypes. Although CIDs are more prevalent in the Middle East than Western countries, the resources for genetic diagnosis are limited. Objectives This study aims to characterize the categories of patients with CIDs in Iran clinically and genetically. Methods Clinical and laboratory data were obtained from 696 patients with CIDs. Patients were subdivided into those with syndromic (344 patients) and nonsyndromic (352 patients) CIDs. Targeted DNA sequencing was performed on 243 (34.9%) patients. Results The overall diagnostic yield of the 243 sequenced patients was 77.8% (189 patients). The clinical diagnosis of hyper-IgE syndrome ( P P = .02), and absence of multiple affected family members ( P = .04) were significantly more frequent in the patients without a genetic diagnosis. An autosomal recessive disease was found in 62.9% of patients, reflecting the high rate of consanguinity in this cohort. Mutations impairing VDJ recombination and DNA repair were the most common underlying causes of CIDs. However, in patients with syndromic CIDs, autosomal recessive mutations in ataxia-telangiectasia mutated (ATM) , autosomal dominant mutations in signal transducer and activator of transcription 3 (STAT3) , and microdeletions in 22q11.21 were the most commonly affected genomic loci. Patients with syndromic CIDs had a significantly lower 5-year survival rate rather than those with nonsyndromic CIDs. Conclusions This study provides proof of principle for the application of targeted next-generation sequencing panels in countries with limited diagnostic resources. The effect of genetic diagnosis on clinical care requires continued improvements in therapeutic resources for these patients.

Background Intravenous immunoglobulins (IVIg) are the major treatment in inborn errors of immunity (IEI) disorders; However, IVIg infusions show some adverse effects. We aimed to assess the adverse reactions of IVIg infusions. Methods Data of IVIg infusions in IEI patients were collected from 2011 to 2021. Totally, 363 IEI patients received IVIg regularly in Iran entered the study. The adverse reactions are classified regarding their severity and chronicity. Results 22,667 IVIg infusions were performed in the study. 157 patients (43.2%) and 1349 (5.9%) infusions were associated with at least one type of adverse reaction. The highest rates of adverse reactions were seen in severe combined immunodeficiency. Myalgia, chills, headache, fever, and hypotension were the most frequent adverse effects of IVIg. Conclusion The reactions affect almost half of the patients mainly in the first infusions which necessitate the close observation of IEI patients receiving IVIg.

Immunotherapy is the standard of treatment for long-life relief of symptoms of allergic rhinitis. Vitamin D may affect the outcomes of treatment. This study evaluated the clinical efficacy of subcutaneous allergen immunotherapy in adult patients with allergic rhinitis based on the serum level of vitamin D. Patients with persistent allergic rhinitis and positivity for skin prick test were evaluated by Sino-nasal Outcome Test (SNOT-22) and Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) before subcutaneous allergen immunotherapy and during the maintenance phase to assess the relation of the serum level of vitamin D and the clinical efficacy of immunotherapy. After immunotherapy, the greatest reduction in SNOT-22 scores were reported in patients with vitamin D sufficiency (39.0 ± 9.2), followed by vitamin D suboptimal provision (35.1 ± 12.1), insufficiency (25.0 ± 7.5), and deficiency (18.3 ± 6.0) (P < 0.001). The MiniRQLQ reduction in patients with vitamin D sufficiency, suboptimal provision, insufficiency, or deficiency was 30.7 ± 8.7, 27.1 ± 8.7, 20.0 ± 8.6, or 17.4 ± 7.1, respectively (P < 0.001). Both of SNOT-22 and MiniRQLQ scores decreased significantly following immunotherapy in patients with different levels of vitamin D. However, these effects were more pronounced when the level of vitamin D was sufficient.

Background: Hyper-immunoglobulin M (HIGM) syndrome is a rare heterogeneous group of primary immunodeficiency disorders characterized by low or absent serum levels of IgG and IgA along with normal or elevated serum levels of IgM. Methods: Clinical and immunological data were collected from the 75 patients’ medical records diagnosed in Children’s Medical Center affiliated to Tehran University Medical Sciences and other Universities of Medical Sciences in Iran. Among 75 selected patients, 48 patients (64%) were analyzed genetically using targeted and whole-exome sequencing. Results: The ratio of male to female was 2.9:1. The median age at the onset of the disease, time of diagnosis, and diagnostic delay were 10.5, 50, and 24 months, respectively. Pneumonia and lower respiratory tract infections (61.3%) were the most common complications. Responsible genes were identified in 35 patients (72.9%) out 48 genetically analyzed patients. Cluster of differentiation 40 ligand gene was the most mutated gene observed in 24 patients (68.5%) followed by activation-induced cytidine deaminase gene in 7 patients, lipopolysaccharide-responsive and beige-like anchor (1 patient), nuclear factor-kappa-B essential modulator (1 patient), phosphoinositide-3-kinase regulatory subunit 1 (1 patient), and nuclear factor kappa B subunit 1 (1 patient) genes. Nineteen (25.3%) patients died during the study period, and pneumonia was the major cause of death occurred in 6 (31.6%) patients. Conclusion: Physicians in our country should carefully pay attention to respiratory tract infections and pneumonia, particularly in patients with a positive family history. Further investigations are required for detection of new genes and pathways resulting in HIGM phenotype.

Objective: Current treatment options for Allergic Rhinitis (AR) may have their own limitations and side effects. This study aimed to investigate the effects of Ma-al-Shaeer (MS), a novel natural formulation based on Hordeum vulgare, in the treatment of AR compared with Fexofenadine (FX). Methods: A total of 77 patients with AR were divided into two groups: MS group (n=38) and FX group (n=39). The first group received 15 g of dried MS powder, and the second group received 60 mg of FX twice daily for 14 days. At baseline (week zero) and after the 14-day treatment period (week two), both groups were evaluated for sneezing, rhinorrhea, nasal congestion, nasal itching, post nasal drip, eye, throat, or ear symptoms, headache, cough, mental function, quality of life scores, blood eosinophil count and total IgE levels. Rhinitis control assessment tests were conducted at week zero and again at one week after cessation of treatment (week three) in both groups. Results: All symptoms of AR except cough were significantly reduced in both groups; for nasal congestion, post nasal drip, and headache, the MS treatment was found to be superior. Rhinitis control was significantly increased after treatment in both groups (p value < 0.001). Both drugs significantly reduced total IgE levels. There was no significant change in eosinophil count in either group. Conclusion: MS formulation based on H. vulgare may be an effective treatment for AR. Further studies are needed to confirm the effect of MS as an alternative treatment in AR.

Substance P (SP) is a neurotransmitter emitted from neurons that plays a role in the pathogenesis of itching conditions including chronic urticarial (CU). The present research aims to investigate the serum level of S.P among CU patients and compare them with healthy subjects and explore how it correlates with the severity of urticaria. The present research was conducted on 87 CU patients who visited the allergy clinic of Ghaem Hospital, Mashhad, Iran from October 2017 to June 2018. Besides, 86 healthy subjects were recruited as the control group. Background information of patient was collected including age, sex, duration of the disease and the co-occurrence of angioedema. S.P serum level was measured in two groups by ELISA method. In the patients group, the autologous serum skin test (ASST) was performed along with the urticaria evaluation questionnaire include Urticaria Activity Score 7 (UAS7), Urticaria Control Test (UCT) and Chronic Urticaria Quality of Life (CU-Q2OL). Among the patients, the SP serum level showed to be about two times higher than the healthy subjects (p˂0.001). SP showed to be increased as patients’ age grew (p=0.010). In patients with a positive ASST, SP level was higher (p=0.012). No correlation was found between SP and the presence of angioedema among patients. There was no correlation between the SP serum level and the scores obtained from urticaria evaluation questionnaires. SP among CU patients was higher than healthy subjects. SP was also higher among female, older and positive ASST patients. The SP value was not correlated with the severity of urticaria, angioedema. In conclusion, Using SP antagonist drugs could be a potential treatment for chronic urticaria.

BACKGROUND: Predominantly antibody deficiencies (PADs) are the most common primary immunodeficiencies, characterized by hypogammaglobulinemia and inability to generate effective antibody responses. OBJECTIVE: We intended to report most common monogenic PADs and to investigate how patients with PAD who were primarily diagnosed as suffering from agammaglobulinemia, hyper-IgM (HIgM) syndrome, and common variable immunodeficiency (CVID) have different clinical and immunological findings. METHODS: Stepwise next-generation sequencing and Sanger sequencing were performed for confirmation of the mutations in the patients clinically diagnosed as suffering from agammaglobulinemia, HIgM syndrome, and CVID. RESULTS: Among 550 registered patients, the predominant genetic defects associated with agammaglobulinemia (48 Bruton's tyrosine kinase BTK and 6 mu heavy chain deficiencies), HIgM syndrome (21 CD40 ligand and 7 activation-induced cytidine deaminase deficiencies), and CVID (17 lipopolysaccharides-responsive beige-like anchor deficiency and 12 atypical Immunodeficiency, Centromeric instability, and Facial dysmorphism syndromes) were identified. Clinical disease severity was significantly higher in patients with mu heavy chain and CD40 ligand mutations compared with patients with BTK (P = .003) and activation-induced cytidine deaminase (P = .009) mutations. Paralysis following live polio vaccination was considerably higher in patients with mu heavy chain deficiency compared with BTK deficiency (P < .001). We found a genotype-phenotype correlation among patients with BTK mutations regarding clinical manifestation of meningitis and chronic diarrhea. Surprisingly, we noticed that first presentations in most patients with Immunodeficiency, Centromeric instability, and Facial dysmorphism were respiratory complications (P = .008), whereas first presentations in patients with lipopolysaccharides-responsive beige-like anchor deficiency were nonrespiratory complications (P = .008). CONCLUSIONS: This study highlights similarities and differences in the clinical and genetic spectrum of the most common PAD-associated gene defects. This comprehensive comparison will facilitate clinical decision making, and improve prognosis and targeted treatment.

Background Asthma is a chronic respiratory disease that affects more than 300 million people worldwide. Refractory asthma (RA) is characterized by poor control despite adequate treatment. Conditions like RA have led to a renewed interest in non-conventional approaches to managing asthma such as those used in Traditional Persian medicine (TPM). The aim of this trial was to test a TPM formulation including Plantago major seed and Almond gum powder for asthma. Methods Current patients with RA received 5 g of herbal combination (2 g of Plantago major and 3 g of Almond gum powder) which was added to their conventional treatment 3 times a day for 4 weeks. Outcome measures were taken at baseline and 4 weeks including lung function testing and asthma questionnaires: the Asthma control test (ACT) and Asthma quality of life questionnaire (AQLQ). Results 28 participants with average age of 54.7 ± 11.2 years were enrolled in the study. 4 participants withdrew from the trial due to reactions to the herbal formulation. There were increases in FEV1 and FVC post-intervention compared to baseline (p Conclusion The results demonstrate that a combination of Plantago major seed and Almond gum is well-tolerated and potentially beneficial for patients with RA. Further research is warranted to ascertain the mechanisms and therapeutic effects of these ingredients.