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.

Treatment patterns and outcomes in patients with chronic urticaria during pregnancy: Results of PREG-CU, a UCARE study.

BACKGROUND: Although chronic urticaria (CU) is a common and primarily affects females, there is little data on how pregnancy interacts with the disease. OBJECTIVE: To analyse the treatment use by CU patients before, during and after pregnancy as well as outcomes of pregnancy. METHODS: PREG-CU is an international, multicentre study of the Urticaria Centers of Reference and Excellence 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 including standard-dose second generation H1-antihistamines (35.1%), first generation H1-antihistamines (7.6%), high-dose second-generation H1-antihistamines (5.6%) and omalizumab (5.6%). The preterm birth rate was 10.2%; rates were similar between patients who did and did not receive treatment during pregnancy (11.6% vs. 8.7%, respectively). 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. CONCLUSION: Most CU patients used treatment during pregnancy especially second-generation antihistamines which seem to be safe during pregnancy regardless of the trimester. The rates of preterm births and medical problems of new-borns in CU patients were similar to population norms and not linked to treatment used during pregnancy. Emergency referrals for CU increased the risk of preterm birth and emphasize the importance of sufficient treatment to keep urticaria under control during pregnancy.

The effects of Alpha-2a and Beta-1a Interferons on the Coronavirus disease 2019 prognosis.

BACKGROUND: The pandemic coronavirus disease 2019 (COVID-19) has been associated with substantial mortality worldwide. Efforts have continued to find an effective treatment for COVID-19. In vitro activity of interferon (IFN) subtypes has been shown against the SARS-CoV and MERS-CoV. Furthermore, the superiority of IFN-ß over IFN-α2b and IFN-α2a has been demonstrated in MERS treatment. Early studies showed a low plasma level of IFNs in the peripheral blood or lungs of patients with severe COVID-19. This study assessed the effects of IFN-alpha-2a and -beta-1a on the prognosis of patients with covid-19 infection. METHODS: We conducted a triple-blind randomized clinical trial on adult patients with moderate to severe COVID-19 from April 2021 to June 2021. The patients were diagnosed based on clinical and laboratory findings and randomly assigned into four groups (A, B, C, and D) using the envelope allocation method. Patients in group A received IFN ß-1a; group B received IFN ß-1a placebo; group C received IFN α-2a, and group D was treated with IFN α-2a placebo. All patients concomitantly received the national protocol medications as well. RESULTS: A total of 95 eligible patients were randomly assigned into groups. National Early Warning Score 2 (NEWS2) index showed significant differences between groups only on the first day of admission (p-value = 0.001). CT scan scores on the first and tenth days slightly improved, although they were not statistically significant. Duration of hospitalization and hospital discharge did not significantly differ among all treated groups (Table 1). Mortality rates showed no significant statistical difference between the groups. However, viral clearance significantly accelerated in the patients receiving IFN ß-1a or IFN α-2a (p < 0.05). CONCLUSION: It seems that IFN α-2a and IFN ß-1a are ineffective in treating COVID-19 patients. Further randomized clinical trials with large sample sizes are needed to estimate the effects of IFN α-2a or IFN ß-1a on the outcomes of COVID-19 disease.

The impact of propolis on clinical manifestations and specific IgE levels against salsola in perennial-allergic rhinitis patients.

Objectives: Propolis has an anti-inflammatory effect induced by inhibiting cyclooxygenase, subsequent inhibition of prostaglandin and nitric oxide synthesis, reduction of inflammatory cytokines, and eventually immunosuppressive activity [1-3]. This study aims to evaluate the impact of propolis on clinical features and specific IgE levels against salsola in perennial allergic rhinitis patients. Methods: Thirty patients diagnosed with perennial allergic rhinitis with salsola-positive skin prick test were enrolled in this randomized controlled clinical trial and divided into two groups. The intervention group received the propolis (200 mg per day), and the control group received a placebo for four months, besides intranasal corticosteroids. At baseline and the end of the intervention, the level of Salsola-specific IgE was measured by the RAST method. To assess the propolis effect on the quality of life and disease severity, miniRQLQ and SNOT22 questionnaires were completed by patients before and after the intervention. Results: According to Table 1, Serum IgE level showed decreasing changes (-0.057) despite increasing changes in the control group (1.039). However, these differences were not statistically significant (P = 0.967). Based on the miniRQLQ questionnaire, quality of life improved in both groups without any significant difference (P = 0.930). According to the SNOT-22 questionnaire, both groups' nasal and sinus problems decreased significantly. However, the intervention type did not affect this decrease and was observed over time in both groups (P> 0.05). Conclusion: Propolis supplementation did not significantly affect various laboratory parameters, clinical symptoms, and quality of life of patients with allergic rhinitis.

Risk factors for systemic reactions in typical cold urticaria: Results from the COLD-CE study.

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® 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.

Adrenaline autoinjector is under-prescribed in typical cold urticaria patients living in tropical climate countries.

Background: The diagnosis of typical cold urticaria (ColdU) relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold-induced anaphylaxis (ColdA). Till date, it is largely unclear how often patients with ColdU receive adrenaline treatment and are provided with an adrenaline autoinjector (AAI). Methods: An international, cross-sectional study, COLD-CE (i.e., comprehensive evaluation of ColdU and other cold-induced reactions), was carried out at 32 UCAREs. Detailed histories were taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold-induced (i.e., by cold water, air, or surfaces) involvement of the skin and/or visible mucosal tissue and at least one of the symptoms (cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms). Results: Of the 551 ColdU patients, 75% (n = 412) had a positive CST. Of them, concomitant chronic spontaneous urticaria was diagnosed in 10%. Of 372 patients with stand-alone ColdU, 69% were women and 91% adults. Their median age was 36 (IQR 26 - 48) years. Patients were also categorized into residents of countries with a tropical (n = 33), temperate (n = 264), or cold (n = 75) climate (Table 1: R13C1, R17C1, R21C1). AAI was more often prescribed to residents of temperate than tropical countries (30% vs. 12%, p = .038; Table 1: R31C1), although the frequency of ColdA did not significantly differ between these countries (44% vs. 42%, p = 1.000; R29C2). Residents of tropical countries had a higher frequency of ColdA induced by cold air than residents of temperate (36% vs. 12%, p = .001; R29C4) or cold (36% vs. 12%, p = .007; R25C4) countries. Cardiovascular manifestations induced by cold air were diagnosed in 33% (n = 11) of residents of tropical countries, but only 18% (n = 2) and 36% (n = 4) of them had received adrenaline and AAI, respectively (R13 - 15C7). Furthermore, hypotension and/or loss of consciousness induced by cold air occurred in 18% (n = 6) of patients, but only 17% (n = 1) received adrenaline (R13 - 14C10). ColdA was induced by complete cold water immersion in 9% (n = 3) of patients, and none of them received adrenaline treatment nor AAI (R13 - 15C3). Conclusion: Our findings suggest that ColdA is undertreated and call for changes in ColdU management.

Adverse reactions in a large cohort of patients with inborn errors of immunity receiving intravenous immunoglobulin.

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.

Effects of pregnancy on chronic urticaria: Results of the PREG-CU UCARE study.

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.

Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity.

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, immunologic, 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%), and 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 to discover responsible genes for the immune dysregulation at an early stage of the disease.

Significant association between Taq1 gene polymorphism in vitamin D receptor and chronic spontaneous urticaria in the Northeast of Iran.

OBJECTIVE: Chronic spontaneous urticaria (CSU) is defined as urticaria with an unknown etiology which persists for more than 6 weeks. CSU is an uncomfortable cutaneous condition that occurs due to an immune-mediated inflammatory reaction. Many studies have demonstrated that vitamin D deficiency and single-nucleotide polymorphisms in the vitamin D receptor (VDR) impact the immune response. In the current study, the frequency of the Taq1 polymorphism in the VDR gene were compared between patients with CSU and individuals without CSU. METHODS: In a case-control study, a group of CSU patients (n = 100) was compared with a group of healthy age- and gender-matched individuals as a control group (n =100) who visited our center between 2015 and 2017. After DNA extraction from EDTA-containing blood, polymerase chain reaction (PCR-RFLP) was used to determine the presence of the Taq1 polymorphism. Serum vitamin D levels were measured using ELISA method (Abcam, Cambridge, USA). RESULTS: Genotyping for Taq1 polymorphism showed that TT, Tt and tt genes frequency in the CSU group were 36%, 54%, and 10% respectively. The TT, Tt and tt genotypes had a distribution of 50%, 47% and 3% respectively in the control group. The mean serum vitamin D level in the CSU group was 19.88 ± 8.14 ng/ml, which was not significantly correlated with the Taq1 polymorphism (P = 0.841). There was a significant relationship between Taq1 gene polymorphism (tt genotype) and CSU (P = 0.038). Tt genotype increased the risk of CSU (odds ratio = 1.596), and inheritance of tt genotype increased the risk even further (odds ratio = 4.630). CONCLUSION: The frequency of Taq1 genotype polymorphism in the VDR gene was significantly higher in patients with CSU compared to the control group. The tt genotype polymorphism may be a risk factor for CSU.

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity.

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.

Clinical Manifestations, Immunological Characteristics and Genetic Analysis of Patients with Hyper-Immunoglobulin M Syndrome in Iran.

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.

Clinical, immunologic, and genetic spectrum of 696 patients with combined immunodeficiency.

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 < .001), onset of disease at greater than 5 years (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.

Investigation of the relationship between atopy and psoriasis.

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.

Fourth Update on the Iranian National Registry of Primary Immunodeficiencies: Integration of Molecular Diagnosis.

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Evaluation of serum interleukin- 35 level in children with persistent asthma.

BACKGROUND: IL-35 is a novel cytokine suppressing the immune response through the expansion of regulatory T cells and suppression of Th17 cell development. Few studies have been done on the effect of this cytokine in a different disease. Asthma is a complex disease that many inflammatory cells and cytokines play a role in. OBJECTIVE: We decide to determine the difference between serum level of IL-35 in childhood asthma & healthy children. METHOD: We obtained serum samples from 44 asthmatic children between 2 and 15 years as a case group and from healthy children as a control group. IL-35 serum concentration was determined by ELISA method in both groups. RESULTS: Mean serum level is 30.9 pg/ml in the case group and 30.2 pg/ml in the control group. There is no significant difference between serum level of IL-35 in asthmatic & healthy children. CONCLUSIONS: Our data reveal no relation between childhood asthma and serum level of IL35. So, further study will be needed to clarify effects of this cytokine in human allergic diseases.

Level of Agreement between Children with Asthma and their Parents on Quality of Life.

BACKGROUND: Child-parent agreement is a controversial aspect of measuring health-related quality of life (HRQoL) in children and adolescents. The aim of this study was to assess the agreement between the child self-reports and parent proxy reports of the PedsQL 3.0 Asthma Module in Iranian children with asthma to evaluate HRQoL. Moreover, the psychometric properties of the child and parent reports of the PedsQL 3.0 Asthma Module were assessed in the present study. METHODS: Participants were 112 children with asthma and their parents, who completed the Farsi version of the PedsQL 3.0 Asthma Module. The multitrait-multimethod correlation matrix and factor analysis were used to test whether the child self-reports and the parent proxy reports measured the same construct. Additionally, convergent and discriminant validity and internal consistency were assessed using the Pearson correlation. RESULTS: The correlation between the child and parent HRQoL perceptions ranged between 0.13 and 0.36 across the same domains. Our factor analysis revealed that the child self-reports and the parent proxy reports measured 2 different constructs of HRQoL. Furthermore, our findings showed that both the child self-reports and the parent proxy reports of the PedsQL 3.0 Asthma Module had excellent internal consistency and acceptable convergent and discriminant validity. CONCLUSION: Although the child self-reports and the parent proxy reports of the Farsi version of PedsQL 3.0 Asthma Module showed good psychometric properties, they were not interchangeable. Our children with asthma and their parents evaluated child HRQoL from their own viewpoints.

Fluctuation of Disease Severity and Quality of Life Applying Intralymphatic Immunotherapy for Patients with Seasonal Allergic Rhinitis.

Allergen-specific immunotherapy is the only disease-modifying treatment for IgE-mediated allergic disorders. Intra lymphatic immunotherapy (ILIT) is an efficacious 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.  In this clinical trial, patients between 18 and 65 years old with moderate to severe allergic rhinitis were enrolled. They received monthly intra-lymphatic inguinal injections of an active allergen (1000 SQ-U Salsola kali pollen). Their clinical symptoms were assessed before and four weeks after treatments. The clinical signs were also evaluated during two consecutive pollination seasons and the following non-pollination season in April. No moderate or severe reactions were recorded following ILIT treatment. Lymph node enlargement, angioedema/urticaria, and local itching were seen instantly after injection. Patients who received ILIT experienced a significant clinical improvement in self-recorded seasonal allergic symptoms after the treatments, compared to themselves before ILIT. Furthermore, their quality of life significantly improved. This study suggests ILIT with Salsola-pollen extract may decrease symptoms of allergic rhinitis. It was safe and did not cause any crucial complications.

Non-Skin Related Symptoms Are Common in Chronic Spontaneous Urticaria and Linked to Active and Uncontrolled Disease: Results From the Chronic Urticaria Registry.

BACKGROUND: Chronic spontaneous urticaria (CSU) can present with non-skin related symptoms (NSRS), including recurrent unexplained fever, joint, bone, or muscle pain (JBMP), and malaise, which also occur in other conditions that manifest with wheals (eg, urticarial vasculitis or autoinflammatory disorders) or without wheals (eg, infection). OBJECTIVE: We sought to determine the rate of patients with CSU affected by fever, JBMP, and malaise, their trigger factors, links with clinical and laboratory characteristics, and their impact on everyday life and treatment responses. METHODS: We analyzed baseline data from the Chronic Urticaria Registry of 2,521 patients with CSU who were aged 16 years or older. RESULTS: One third of CSU patients (31.2%; 786 of 2,521) had one or more NSRS, including recurrent fever (5.3%), JBMP (19.1%), and/or malaise (18.6%). In a multivariable analysis, having one or more of these NSRS correlated with food and infection as trigger factors of urticaria (adjusted odds ratio [aOR] = 1.7 and 1.5), wheals of 24 hours or greater duration (aOR = 2.5), sleep disturbance (aOR = 2.4), anxiety (aOR = 2.8), comorbid atopic dermatitis (aOR = 2.1), gastrointestinal disease (aOR = 1.8), elevated leukocytes (aOR = 1.7) and erythrocyte sedimentation rate (aOR = 1.5). In a bivariate analysis, these NSRS were additionally associated with higher disease activity (weekly Urticaria Activity Score, median: 21 vs 14; P = .009), longer disease duration (years, median: 2 vs 1; P = .001), the presence of angioedema (74.6% vs 58.7%; P < .001), worse quality of life (Chronic Urticaria Quality of Life Questionnaire, median: 42 vs 29; P < .001) and more frequent poor control of CSU (78% vs 69%; P < .001). CONCLUSIONS: The presence of NSRS in a subpopulation of patients with CSU points to the need for better control of the disease, exclusion of comorbid conditions, and/or exclusion of urticarial vasculitis and urticarial autoinflammatory diseases.