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Objective Sesame allergy is the most prevalent allergy to seeds. Oral immunotherapy (OIT) is defined as continuous consumption of an allergen at special doses and time. Omalizumab (Anti-IgE) increases tolerance to allergens used in OIT. This study evaluated the effectiveness of a new sesame OIT protocol in patients with sesame anaphylaxis in combination with omalizumab. Methods In this prospective open-label interventional trial study, 11 patients with a history of sesame anaphylaxis were enrolled after approval by Oral Food Challenge (OFC) test. At baseline, skin prick test (SPT) and skin prick to prick (SPP) test were performed. Serum sesame-specific IgE (sIgE) levels were measured. The maintenance phase was continued at home with daily sesame intake for 4 months. At the end of month 4, the OFC and above-mentioned tests were repeated to evaluate the treatment effectiveness. Results All 11 patients who underwent sesame OIT after 4 months could tolerate a dietary challenge of 22 ml tahini (natural sesame seed, equal to 5,000 mg of sesame protein and higher) and the average of wheal diameter in the SPT and SPP tests significantly decreased after desensitization. Conclusion This OIT protocol may be a promising desensitization strategy for patients with sesame anaphylaxis. Also, omalizumab obviously reduced the severity of reactions.

BACKGROUND Oral immunotherapy (OIT) is under consideration as a promising treatment for desensitization of egg-allergic patients. The objective of this study was to assess the effectiveness of egg-white OIT in patients with IgE-mediated allergy to egg white and to compare the clinical and laboratory findings before and after OIT. METHODS This clinical trial was performed from February to August 2018 in Rasool e Akram Hospital, Tehran, Iran. Patients' selection criteria included a history of allergic symptoms, skin prick test (SPT) reactivity to egg white, and the inability to pass the Oral Food Challenge (OFC). Egg-white OIT was done for eight patients in the OIT group for 6 months while egg-white-free products were administrated for controls. The SPT reactivity, specific IgE, and IgG4 for egg white and ovomucoid were evaluated before and after OIT. RESULTS Hundred percent of the subjects in OIT group were desensitized and tolerated 40 cc raw egg white following 6-month maintenance whereas none of the controls was able to pass the OFC. The findings obtained from the evaluations indicated a significant decrease in the wheal size and specific IgE to egg white after OIT (P = .001). Furthermore, a significant decrease of IgE/IgG4 ratio to egg white was found in OIT group (P = .01). CONCLUSION This OIT protocol was successful as all OIT patients were able to continue 6-month OIT process and the reaction threshold to egg white increased in the OIT group. Therefore, it could be regarded as an effective and safe protocol to treat egg-allergic patients.

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 it is estimated that COVID-19 life-threatening conditions may be diagnosed in less than 1:1000 infected individuals below the age of 50, but the real impact of this pandemic on pediatric patients with different types of primary immunodeficiency (PID) is not elucidated. The current prospective study on a national registry of PID patients showed that with only 1.23 folds higher incidence of infections, these patients present a 10-folds higher mortality rate compared to population mainly in patients with combined immunodeficiency and immune dysregulation. Therefore, further management modalities against COVID-19 should be considered to improve the survival rate in these two PID entities using hematopoietic stem cell transplantation and immunomodulatory agents. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-020-00928-x.

Allergic proctocolitis is a cell-dependent food allergy that is present in both breast and formula-fed infants. The presence of blood with different amounts in the stool is the main manifestation of the disease. Different results have been published on the accuracy and specificity of the atopic patch test (APT). The purpose of this study was to evaluate the results of the APT and compare them with those obtained in the food elimination/introduction (E/I) challenge, as the gold standard of confirming the allergy. Twenty-eight patients (18 boys, 10 girls

Cystic fibrosis (CF) is a hereditary syndrome composed of exocrine gland dysfunction involving multiple systems which if untreated may result in chronic respiratory infections, pancreatic enzyme deficiency and failure to thrive. The association between CF and other inherited diseases or congenital anomalies is rare. We describe a rare case of CF with concomitant congenital adrenal hyperplasia (CAH). 21- Hydroxylase deficiency accounts for most CAH cases. Varity in clinical phenotypes depends on the amount of enzymatic activity which in turn depends on different combination of gene mutations. The genes of CAH and CF are located in different locations. The chance of these diseases coexisting in our patient would be a rare combination. However, such a case will be more frequent in our population than others because of consanguineous marriage and common ancestors. There are diagnostic difficulties, similarities and contradictions between two diseases and they are pointed out.

Introduction: Netherton Syndrome (NS) is a rare hereditary autosomal recessive disorder with ichthyosiform cutaneous lesions, specific hair shaft defect, and atopic diathesis. The incidence of NS is estimated to be approximately 1 in 200000. The objective of this case report is to present NS in a patient with severe eczema atopic dermatitis-like eruption. Case Presentation: A 41-month-old boy was referred to the clinic of Allergy and Immunology, Hazrat Rasoul Hospital with generalized erythema, and scaling cutaneous lesions. The patient underwent clinical examinations and laboratory analysis. His laboratory data revealed only an elevated IgE level with a leukocyte count of 7800/μL containing 10% eosinophil. His hair shaft indicated classic trichorrhexis invaginata (Bamboo hair). Based on the clinical and laboratory findings, he was diagnosed with NS. A brief review was also done related to this case. Conclusion: This case was reported because of the severity of the disorder and other differential diagnoses in severe and refractory atopic dermatitis-like eruptions. The importance of the case is related to other differential diagnoses, especially with early onset disorders at neonatal age. Log in to use Ginger Limited mode ichthyosiform ×

Background: We aimed to determine the epidemiology of anaphylaxis to bee stings in the rural areas of Gorgan City, Iran. Objectives: Anaphylaxis is a severe, life-threatening, diffuse or systemic hypersensitivity reaction with rapidly progressive problems such as airway (throat or laryngeal edema) or bronchospasm, tachypnea and hypotension .The systemic response to bee stings is 1% in children and 3% in adults. Anaphylaxis due to bee stings is very dangerous in many cases, and may even be fatal at the initial stage. Methods: In this cross-sectional study, we analyzed some of the epidemiological characteristics of the study participants, such as demographic information, bee type, the cause of anaphylaxis, the time of bee sting, the onset of symptoms of anaphylaxis after a bee sting, the number of bee stings, symptoms during anaphylaxis, and therapeutic and prophylactic measures. Results: In total, 201 patients were diagnosed with anaphylaxis caused by bee stings. Of these, 129(64%) were male, and 72(36%) were female with the Mean±SD age of 34.33±32 and 35.25±34 years, respectively. Anaphylaxis incidents occurred in 108 men, and 103 women out of 100000; 169 of whom were adults and 46 were children. Anaphylaxis occurred in 105(52.2%) cases in

The recombination activating genes, including RAG1 and RAG2, are essential for V(D)J somatic recombination in lymphocytes. Leaky severe combined immunodeficiency disorder (SCID) is characterized by normal or intermediate T cells and normal to absent B cells associated with partial T cell and B cell dysfunction. We present a newly found RAG1 deficiency in a 21-year-old boy with leaky SCID. Immunoglobulin levels, flow cytometry, and whole exome sequencing (WES) were evaluated. Flow cytometric analysis revealed a decreased number of CD3+, CD4+, and CD8+ T cells, and B cells whereas NK cell counts were normal. Immunoglobulin levels were also decreased. The WES revealed a newly found homozygous mutation of RAG1 gene (NM_000448: exon 2: c.C2275T). Atypical features, including leukopenia, candidiasis, and low lymphocyte counts in patients with late-onset combined immunodeficiency disorders (CID) such as leaky SCID due to RAG1 deficiency may result in misdiagnosis and inadequate therapy instead of adopting the curative hematopoietic stem cell transplantation in these patients.

Good's syndrome is a rare adult‐onset thymoma‐associated immunodeficiency with unknown pathogenesis. Therefore, it should be carefully managed as soon as possible when complications are presented. Because of variety of immunodeficiency, this syndrome is now classified as a separate entity with a broad classification (immunodeficiency with thymoma).

Hereditary angioedema (HAE) is characterized by recurrent attacks of skin and mucosal swelling in any part of the body including the digestive and respiratory tract which generally improve spontaneously within 12-72 hours. The underlying mechanism in HAE is related to bradykinin dysregulation which causes these attacks not to respond to common treatment strategies including epinephrine or corticosteroid. There are several types of HAE with different etiology but with the same clinical picture. Type 1 is due to the deficiency of C1 Inhibitor (C1- INH) protein and type 2 is related to dysfunctional C1-INH protein. The third type of HAE which comprises the minority of cases is associated with the normal amount and function of C1- INH protein. The presented case in this report was a 15-years old girl with a history of spontaneous angioedema attacks from the age of 14. The frequency of attacks was initially every two months but consequently increased to every two weeks after using some hormonal medications for ovarian cyst. Each episode has lasted around 10 days without any symptoms in between. Complement studies including C4, C1q, and C1-INH protein, both quantitative and qualitative, were reported as normal. A genetic assessment revealed a mutation in the exon 9 on the gene related to factor XII, hence the diagnosis of HAE type 3 was confirmed. This was a rare type of angioedema with normal amount and function of C1-INH protein which is predominantly seen in women during periods of imbalanced estrogen increments like pregnancy, lactation, and menopause, and hence it is responsive to hormonal manipulation strategies such as the use of progesterone containing medications.

Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disease that may be triggered by some diseases and medications. For the latter one, non-steroidal anti-inflammatory drugs (NSAIDs) have been identified as one of the potential causative agents to develop LABD. Here, a rare case of drug-induced LABD is introduced. A 13-month-old Iranian boy presented with a history of generalized blisters, displaying the classic “string of pearls” sign who was eventually diagnosed as a case of LABD. In his admission, he was diagnosed whit Mucocutaneous lymph node syndrome and treated with aspirin. Some features like appearing the characteristic lesions one week following the administration of aspirin, rapid clearance of lesions after the withdrawal of the drug, and reappearance of new lesions after readministration of aspirin were highly suggestive of aspirin-induced LABD. To establish the diagnosis, we used the “Naranjo probability score” which determined the probable causative role of aspirin. The diagnosis was confirmed by showing the positive IgA deposition in the basement membrane zone in a direct immunofluorescence study of the skin biopsy. The child was treated with dapsone with dramatical response to the drug.

Background: Rhinosinusitis is a nasal and paranasal sinus infection. Chronic infection and allergies are two major causes of nasal polyp formation. Objectives: In this study, we examined the relationship between NO and aeroallergens to determine the relationship between exhaled nitric oxide level and sensitivity to aeroallergens in chronic rhinosinusitis with nasal polyps (CRSwNP) patients referring to Hazrat Rasool Hospital in Tehran from December 2016 to May 2017. Methods: A cross-sectional study was conducted on 72 patients. The prick test and exhaled NO measurements were done to determine allergens in CRSwNP patients. Statistical analysis was done to determine the relationship between the allergy and sensitivity to indoor aeroallergens in patients with CRSwNP. Results: The correlation coefficient of. 0.014 and 0.001 were evaluated for Mosquito and Cockroach respectfully, which were significantly correlated with nitric oxide. The less correlation with nitric oxide was 0.003, which was evaluated for MUCOR. Conclusions: This study showed that most people with CRSwNP had a sensitivity to at least one indoor aeroallergen, and cockroaches were the most common allergen in patients with CRSwNP with a 17.9% prevalence. This study showed that the correlation of FeNO with the sensitivity of these patients to home aeroallergens can be used, and this correlation for mosquito and cockroach aeroallergens is very valuable. The NO level and prick testing of aeroallergens can be used to estimate the relapse or lack of appropriate response to medical treatment in patients with CRSwNP.

Asthma induced by ingestion of aspirin occurs when symptoms arise within 30 minutes to three hours after aspirin consumption. Previous data indicate that sensitivity to aspirin may be associated with poorly controlled asthma. This study aims to evaluate the frequency of aspirin sensitivity in patients with moderate to severe asthma receiving conventional asthma therapy. This clinical trial was conducted on 65 patients aged 18 to 65 years with moderate to severe asthma from February 2015 to February 2016 at the Allergy Department, Hazrat-e-Rasoul Hospital, Iran University of Medical Sciences, Tehran. To assess treatment responses in patients, forced expiratory volume in the first second (FEV1) and asthma control test (ACT) scores were measured at baseline and after 3 months. The results of the oral aspirin challenge revealed a prevalence of 35.38% for sensitivity to aspirin. Hypersensitivity reactions to aspirin were detected in 60.9% of the patients with moderate asthma and 39.1% of the patients with severe asthma. All patients with positive aspirin challenge tests suffered from rhinosinusitis and in 56.5% of cases, history of previous hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) was detected. No meaningful differences were found between those patients with aspirin sensitivity and those with aspirin tolerance neither in mean prebronchodilator FEV1 nor in ACT scores pre- and post-treatment. To conclude, aspirin sensitivity was not found to have an association with an unfavorable response to conventional treatment in patients with uncontrolled asthma.

Background: Asthma is a disease with chronic airway inflammation, whereby the airway hyper-reactivity increases. Oxidative stress balance plays a critical role in asthma. Objectives: The present study aimed to evaluate serum glutathione peroxidase (GPX) enzyme activity and selenium levels in patients with asthma. Methods: This case-control study was conducted on 64 children aged 1 - 5 years, 32 subjects as controls, and 32 subjects with asthma who were selected randomly. The serum GPX activity and selenium levels of the studied subjects were determined spectrophotometrically. Results: The present study showed that serum GPX activity and Se levels of patients with asthma were significantly lower than those of controls (P < 0.001, P < 0.05, respectively). Conclusions: Reduction of serum GPX activity and Se concentration in patients could have a potential role in the pathogenesis and modulation of asthma. Micronutrient supplementation of Se may be beneficial in asthma.

To the EditorAt present, strict food avoidance is the only standard treatment for food anaphylaxis. Incidental exposure, cross-contamination, incomplete adherence, nutrient and psychological deprivations in parallel to significant quality of life impairment of the patient and his/her family led to many attempts to find alternative therapies, including oral immunotherapy (OIT) that showed promising clinical implications [1]. During OIT, gradually increasing doses from very small amounts are given to the patient at specified intervals until a predetermined final dose is reached (build-up phase). If the patient reaches this final dose, he/she has to take this maintenance continuously in a regular daily schedule (maintenance phase). An allergic reaction as mild as local pruritus of the lips or as severe as anaphylaxis is the main limitation of both phases. The primary consequence during OIT is the reduction of anaphylaxis risk in accidental exposures and the second consequence is the achievement of permanent tolerance (PT)[2].During desensitization, unresponsiveness is accessible as long as the patient adheres to the instructions, while during PT, unresponsiveness is independent of adherence to the schedule. Natural tolerance (NT) is seen in infants with food allergy and develops with increasing the age but inducible permanent tolerance (IPT) is seen in some patients doing OIT [2, 3]. Currently, not only the immunologic mechanisms or prognostic factors in success or failure of OIT and the achievement of PT are not fully understood but also it is not clear that inducible permanent tolerance really works like natural tolerance? How can we say to a patient with food anaphylaxis that he/she is definitely cured? Therefore, we designed this study to assess the possible reactions of patients with anaphylaxis after the achievement of PT.This prospective cohort study was conducted on patients with cow’s milk anaphylaxis who underwent OIT in the Allergy and Clinical Immunology Department of Rasoul-e-Akram Hospital, Tehran, Iran [4]. All of the participants or their parents signed written informed consent form and the Ethics Committee of Iran University of Medical Sciences approved this study (IR.IUMS.FMD.REC.1397.333). Twenty-one patients who met the inclusion criteria, including cow’s milk anaphylaxis, successful OIT with more than 48 months of the maintenance phase, complete adherence to maintenance phase protocol were allocated to this study. After 4 weeks of complete dairy avoidance, they underwent a standard oral food challenge (OFC) [5]. Eight out of 21 individuals who could pass the OFC were diagnosed as PT and approved for this study.In the first week, they were asked to take a double and triple amount of the maintenance dose in the hospital. All of them consumed this amount of milk without any reaction and then they were asked to take any amount of cow’s milk or dairy products regardless of timing similar to non-allergic individuals. They were given a 24-hour contact number to report any symptoms immediately, and we followed them weekly by phone for 6 months. Any kind of reactions, the severity of symptoms, type of relieving drug, the interval of usage, amount of milk consumption, and the existence of aggravating factors such as exercise, fever, and infection was monitored. All of them showed a significant decrease in specific IgE and IgG4 to cow’s milk before and after the OIT. Seven of eight participants showed some reactions after cow’s milk consumption. Reactions were mild and only oral antihistamines were used for treating the reactions. All of the symptoms were appeared along with exacerbating factors. Cow’s milk consumption without aggravating factors was safe independent of the amount and interval of the consumption. Exercise in the first hour after drinking milk was the most common trigger in our participants. Data are shown in table 1.We conducted a prospective cohort study in cow’s milk anaphylactic patients with successful OIT. Out of 21 patients, only 8 cases passed the OFC after 4 weeks of cessation of dairy consumption and were diagnosed as PT state [2]. There are two different definitions in OIT. Desensitization refers to a temporary state of unresponsiveness of the adaptive immune system to a specific antigen, which is dependent on continuous use of the predetermined amount of that food, while permanent tolerance is defined as persistent unresponsiveness of the adaptive immune system to that antigen, irrespective of amount and consumption continuity [2, 3]. It is estimated that about 30 to 90% of individual who undergo OIT are able to achieve desensitization state [2, 6] but the rate of PT is unknown and is reported between 28 to 36 % in limited trials [3, 6], it is suggested longer maintenance phase and higher amount of daily use may have some role in PT development [2].In this study, 8 of 21 (38%) patients developed PT. The success rate of PT induction was not our aim. We wanted to provide more information about possible reactions related to milk ingestion after PT achievement. The main question was: Can we really give assurance to patients with anaphylaxis that they are completely safe in the exposure to the culprit food, regardless of the dose and continuity of consumption? To the best of our knowledge, it is the first time to follow these individuals after PT development; however, Nowak-Wegrzyn A and Deborah M [2, 7] also asked this question without a clear response. Allergic reactions are the main side effects during OIT in both escalation and maintenance phases. It is important to consider that in the maintenance phase of desensitization, patients may show severe reactions to previously tolerated doses in association with exercise, viral infection, dosing on an empty stomach, menses, and asthma exacerbation. It is hypothesized that these factors may increase intestinal permeability, thereby leading to loss of protection to the previously tolerated dose, even when the maintenance dose has been achieved regularly [2]. Interestingly, our study showed these factors could affect the unresponsiveness state even when PT has developed; however, none of our patients showed severe reactions. The present study showed the dose and continuous consumption of food allergen were not involved in the reaction after PT development but aggravating factors are still important.Signature1-Saba Arshi, MD, associate professor of allergy & clinical immunology, Allergy department, Rasoul e Akram hospital, Iran University of Medical Sciences, Tehran, Iran,2- Fatemeh Alizadeh, MD, pediatrician, pediatric department, Rasoul e Akram hospital, Iran University of Medical Sciences, Tehran, Iran,3-Mohammad Nabavi, MD, associate professor of allergy & clinical immunology, Allergy department, Rasoul e Akram hospital, Iran University of Medical Sciences, Tehran, Iran,4- Mohammad Hasan Bemanian, MD, associate professor of allergy & clinical immunology, Allergy department, Rasoul e Akram hospital, Iran University of Medical Sciences, Tehran, Iran,5-Sima Shokri, MD, assistant professor of allergy & clinical immunology, Allergy department, Rasoul e Akram hospital, Iran University of Medical Sciences, Tehran, Iran,6-Majid KhoshMirsafa, Phd, assistant professor of immunology, Immunolgy department, medical school, Iran University of Medical Sciences, Tehran, Iran7-Farhad Seif, Phd, assistant professor of immunology, department of allergy & immunology, Academic Center for Education, Culture, and Research, Tehran, Iran8- Morteza Fallahpour, MD, assistant professor of allergy & clinical immunology, Allergy department, Rasoul e Akram hospital, Iran University of Medical Sciences, Tehran, Iran

Background and aim Leukocyte adhesion deficiency type 1 is a rare, autosomal recessive disorder that results from mutations in the ITGB2 gene. This gene encodes the CD18 subunit of β2 integrin leukocyte adhesion cell molecules. Leukocyte adhesion deficiency type 1 is characterized by recurrent bacterial infections, impaired wound healing, inadequate pus formation, and delayed separation of the umbilical cord. Materials and methods Blood samples were taken from 13 patients after written consent had been obtained. Genomic DNA was extracted, and ITGB2 exons and exon-intron boundaries were amplified by polymerase chain reaction. The products were examined by Sanger sequencing. Results In this study, 8 different previously reported mutations (intron7+1G>A, c.715G>A, c.1777 C>T, c.843del C, c.1768T>C, c.1821C>A, Intron7+1G>A, c.1885G>A) and 2 novel mutations (c.1821C>A; p.Tyr607Ter and c.1822C>T; p.Gln608Ter) were found. Conclusions c.1821C>A (p.Tyr607Ter) and c.1822C>T (p.Gln608Ter) mutations should be included in the panel of carrier detection and prenatal diagnosis.

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.

Background: The immunologic profile of chronic urticaria is not only important for diagnostic purposes, but also for therapeutic approaches. This study evaluated the serum levels of Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α) and Interferon-ϒ (IFN-ϒ) in patients with chronic urticaria to find a biomarker.Materials and Methods: Forty-one patients with chronic urticaria referring to the Allergy Outpatient Clinic of Rasoul Akram Hospital and 20 healthy control subjects were enrolled in the study. A questionnaire was filled and the disease activity score was determined in a one-week period for every patient. All patients underwent basic laboratory tests in addition to the Autologous Serum Skin Test. Their serum IL-6, TNF-α, and IFN-ϒ levels were also evaluated.Results: The patients were divided into two groups comprising of 20 and 21 participants according to the results of Autologous Serum Skin Tests. The serum IL-6 levels were elevated in the patients’ group (P=0.015). However, there was no significant difference between the patients with chronic urticaria and healthy controls in the serum levels of TNF-α (P=0.25), and IFN-ϒ (P=0.55), neither in the exact state nor by the Mann-Whitney U test.Conclusion: Serum IL-6 level was elevated in patients with chronic urticaria, but the serum levels of IFN-ϒ and TNF-α were not significantly elevated.

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 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.

BACKGROUND Severe combined immunodeficiency (SCID) is a life-threatening pediatric disease. We report on the clinical evaluation, immunological assessment, molecular analysis, and outcomes of SCID patients in a tertiary referral center in Iran. METHODS From January 2006 to December 2015, we performed a prospective cohort study in which initial screening and advanced immunological tests were carried out on patients suspected of having SCID. Genetic analysis was also performed to confirm the diagnosis. RESULTS A total of 63 patients were diagnosed with SCID (43 male [68.3%]). The median age at onset and diagnosis and diagnostic delay were 40 and 110 and 60 days respectively. A total of 49 patients (77.8%) had a history of BCG vaccination, and of these, one-third experienced BCG-associated complications. The most common clinical manifestations were pneumonia, recurrent oral candidiasis, chronic diarrhea, and failure to thrive. Of the thirteen patients who underwent hematopoietic stem cell transplantation, 8 survived and 5 died before they could receive the transplant. Most patients (34.9%) were classified as having T-B-NK+ SCID and had a mutation in the RAG2 or RAG1 gene. CONCLUSIONS Autosomal recessive SCID is the most common type in Iranian patients. Providing high-quality training to physicians and patients' families to reduce the diagnostic delay should be prioritized. It is also important to raise awareness of live vaccination and to expand stem cell donor registries to speed up the transplantation process.

Sesame food allergy (SFA); especially anaphylaxis, is a life-threatening condition. The accurate diagnosis of SFA is done by skin prick test (SPT), skin prick to prick (SPP) or specific IgE (sIgE) and is confirmed by oral food challenge (OFC). Since there are few studies evaluating and comparing the utility of these methods for diagnosis of sesame anaphylaxis in adult patients, we aimed to compare OFC with diagnostic tests, including SPT, SPP, and sesames IgE; using ImmunoCAP considering the sensitivity and specificity issues in patients with sesame anaphylaxis. Twenty patients with sesame anaphylaxis were diagnosed based on OFC. Then SPT, SPP, and sIgE were evaluated. Sixteen patients had positive OFC; while 4 patients had negative results. Out of 16 OFC+ patients, 7 patients were SPT+, 15 patients were SPP+, and 2 patients had detectable sIgE. A positive SPT indicated 44% sensitivity and 50% specificity. A positive SPP showed 87.5% sensitivity and 75% specificity. A positive ImmunoCAP test demonstrated 12.5% sensitivity and 75% specificity. The AUC of SPP was significant for the diagnosis of sesame anaphylaxis (p=0.038). In conclusion, when the OFC is not possible, the SPP test with natural sesame seed may be applicable in patients with a convincing history instead of the artificial or commercial extracts of sesame used for SPT. Positive SPP is a good alternative diagnostic method for patients with sesame anaphylaxis. Also, the poor sensitivity of SPT and sIgE may indicate the poor discriminative capability of these tests.

Background Common variable immune deficiency (CVID) is a heterogeneous syndrome with a wide variety of signs and symptoms. This study describes the phenotyping and survival of the CVID patients in the allergy and clinical immunology department of Rasol-E-Akram Hospital of Iran University of Medical Sciences in Tehran. Method We retrospectively reviewed hospital files of CVID patients in our department until January 2014. All patients were diagnosed with standard diagnostic criteria of CVID, treated and visited monthly, during the follow-up period. We divided the patients into four phenotypes; infection only, cytopenia, polyclonal lymphocytic infiltration and unexplained enteropathy. The immunologic, demographic and clinical findings in different phenotypes were analysed. Results The study included 47 CVID patients with mean age at onset of symptoms and diagnosis of 11.2 and 20.2 years, respectively. Phenotyping of our patients was: only infection (62%), cytopenia (26%) and PLI (19%) and 94% of cases had only one phenotype. We did not find a significant relation between the clinical phenotypes and immunologic or demographic data. Rate of parental consanguinity in our cases was 47%. Parental consanguinity was related to lower age at onset, lower age at diagnosis and higher baseline IgG levels. Patients with malignancy and autoimmunity had significantly higher age at onset. Our patients were followed-up for 6.9 years and the mortality rate during this time was 6%. Conclusions Parental consanguinity and age at onset of CVID symptoms may have important roles in CVID manifestations.

Summary Eosinophilic esophagitis (EoE) is a chronic allergen/immune-mediated disease leading to esophageal dysfunction. Food allergens play critical roles in the pathogenesis and treatment of EoE via different mechanisms. This study aimed to present the characteristics and evaluate the ability of skin prick test (SPT), skin prick to prick test (SPP) (IgE-mediated), and atopic patch test (APT) (cell-mediated) individually or simultaneously to diagnose food allergy in patients suffering from EoE. This prospective study was conducted on 58 patients with EoE. Seven patients (12.1%) were positive to only one, 3 (5.2%) were simultaneously positive to two, and 32 (55.2%) were simultaneously positive to three tests. Single and double sensitizations were totally 10.4% in IgE-mediated reactions, while 36.5% in cell-mediated reactions. In contrast, poly sensitization (> 2 allergens) was 51.7% in IgE-mediated tests and 20.7% in the cell-mediated test. Multiple sensitization findings showed egg white, milk, yolk, and soy were the most frequent allergens. Our findings indicate that EoE is early onset and associated with multiple food sensitizations, particularly via IgE-mediated mechanisms. These immune-mediated responses encompass both IgE-mediated (SPT and SPP) and cell-mediated (APT) reactions simultaneously not individually. Therefore, employing multiple assays may strengthen the diagnosis of food sensitization.

Introduction: Wheat allergy can develop at any stage of life. The aim of this report was to demonstrate that skin testing and specific IgE have poor specificities and sensitivities for wheat allergy. Case Presentation: A 37-year-old female presented symptoms that were initiated immediately after consumption of bread and biscuits. She was well until two months prior to her recent admission. Her skin prick test, RIDA assay, and patch test for wheat showed negative results despite a history of two episodes of anaphylaxis. She underwent an oral food challenge, which confirmed wheat allergy. A desensitization procedure was recommended for her. At the end of the immunotherapy process, she had normal intake of wheat without any symptoms. Conclusions: Negative sIgE and SPT results do not rule out clinical food allergy. Oral food challenges are still the cornerstone of diagnosis of food allergy.

Hen’s egg, as one of the most common reasons for IgE-mediated food hypersensitivity, affects both children and adults. Taking precautionary measures is suggested for the consumption of other birds’ eggs for patients with allergy to hen’s egg. This paper describes a rare patient with quail egg allergy, which manifested no allergic reactions after oral food challenge with hen’s egg white

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.

The effect of aspirin desensitization (AD) on immunologic profile of patients with AERD has been poorly understood. This study is aimed at investigating the effect of AD on clinical and immunological markers of patients with AERD. This randomized double-blind placebo-controlled trial comprised 34 adult patients (67.6% female) with chronic rhinosinusitis, nasal polyps, and aspirin-intolerant asthma. The active group underwent AD over a 2-day period with increasing doses of aspirin (60, 125, 325, and 625 mg), followed by receiving aspirin 625 mg twice daily for 6 months. Symptom scores and medication needs of patients with AERD who have undergone AD were significantly lower compared to the placebo group after 6 months (7.5 ± 3.5 vs. 10.6 ± 3.8 and 9.3 ± 2.0 vs. 11.0 ± 3.1, respectively, all p < 0.05). However, no significant difference was observed in serum concentration of IL-10, IFN-γ, and TGF-β between two groups neither at baseline nor at the end of study.

Aim: New approaches such as oral immunotherapy (OIT) may be useful in IgE-mediated anaphylaxis to wheat. Patients & methods: 12 patients underwent OIT protocol that comprised of two phases: the first with semolina flour and the second with spaghetti. Total and specific wheat IgE were assayed by ELISA before and after OIT and 18 months later. Skin prick tests were also performed. Results: Patients successfully tolerated 50 g of wheat. The median baseline total IgE was decreased after up-dosing phase and decreased after follow-up (p < 0.01). The median baseline wheat-specific IgE was increased after up-dosing and decreased after follow-up (p < 0.001). Conclusion: The efficiency and safety of our OIT protocol were shown on wheat allergic patients but further investigation is needed.

Heterozygous gain-of-function (GOF) mutations in the signal transducer and activator of transcription 1 (STAT1) have increasingly been identified as a genetic cause of autosomal-dominant (AD) chronic mucocutaneous candidiasis (CMC). In this article, we describe a 33-year-old man who experienced chronic refractory candidiasis, recurrent otitis media, and pneumonia resulting in bronchiectasis, severe oral and esophageal candidiases with strictures associated with hypothyroidism and immune hemolytic anemia. His son also suffered from persistent candidiasis, chronic diarrhea, poor weight gain, and pneumonia that resulted in his demise because of sepsis. The immunological workup showed that an inverse CD4/CD8 ratio and serum immunoglobulins were all within normal ranges. The laboratory data revealed failure in response to Candida lymphocyte transformation test. In addition, by Sanger sequencing method, we found a heterozygous mutation, Thr385Met (T385M), located in the DNA-binding domain of STAT1, which was previously shown to be GOF. These findings illustrate the broad and variable clinical phenotype of heterozygous STAT1 GOF mutations. However, more clinical information and phenotype–genotype studies are required to define the clinical phenotype caused by AD STAT1 GOF.

Familial hemophagocytic lymphohistiocytosis (FHL) is a genetically heterogeneous hyperinflammatory syndrome, caused by an uncontrolled and ineffective proliferation and activation of T-lymphocytes, NK-cells, and macrophages that infiltrate multiple organs. Herein, a patient is presented who suffered from hepatitis and atypical brain lesions. Genetic studies revealed a homozygous mutation in the STXP2 gene; and thus, the diagnosis of FHL5 was confirmed.

Background Vitamin D is hypothesized to have some roles in innate and adaptive immunity, inflammation reduction, and remodeling; therefore, it is supposed to affect the asthma phenotype, severity, and response to inhaled corticosteroid (ICS). Objective To explore the synergistic effects of vitamin D supplementation in addition to asthma controllers (ICS or ICS plus long-acting β-agonist) on airway functions. Methods A randomized clinical trial was conducted in 130 individuals aged 10 to 50 years who lived in Tehran during a 24-week period. Data on age, sex, body mass index, stage of asthma, serum total IgE, history of allergic rhinitis, atopic dermatitis, food allergy, and urticaria were collected. Spirometric parameters (forced expiratory volume in 1 second [FEV 1 ] and ratio of FEV 1 to forced vital capacity) and serum vitamin D measurement were obtained before and 8 and 24 weeks after the intervention. Patients were divided in 2 groups randomly. Both groups received asthma controllers (budesonide or budesonide plus formoterol) according to their stage, but the intervention group received vitamin D supplementation (100,000-U bolus intramuscularly plus 50,000 U orally weekly) in addition to asthma controllers. Results FEV 1 improved significantly in both groups after 8 weeks, but no significant difference was found between the 2 groups at baseline ( P = .20) or after 8 weeks ( P = .99); however, a significant improvement was seen in the intervention group in the last 16 weeks, and FEV 1 was significantly better in the intervention group than the other group after 24 weeks ( P Conclusion Vitamin D supplementation associated with asthma controllers could significantly improve FEV 1 in mild to moderate persistent asthma after 24 weeks. Trial Registration irct.ir Identifier: IRCT201302079608N1.

Background This study was performed to investigate the serum level of interleukin (IL)-13, IL-4, and interferon (IFN)-γ in chronic rhinosinusitis with nasal polyps (CRSwNP) and subsequent inflammation pattern and comorbidities including asthma and aspirin intolerance. Methods A case–control study was conducted on 60 adult patients with CRSwNP with mean age of 37.7 ± 12.7 (ranging from 18 to 70) years, and on 20 healthy controls. Serum levels of IL-13, IL-4, and IFN-γ were assessed, using enzyme-linked immunosorbent assay to be compared between case and control groups. Serum level of total immunoglobulin (Ig) E was also assessed in the patients with CRSwNP. Results Serum level of IL-13 in the patients with CRSwNP was significantly higher than the controls (0.98 ± 1.56 vs. 0.34 ± 0.16 pg/ml, respectively, p = 0.002). IL-4 and IFN-γ did not differ significantly between the two groups. Total IgE level was significantly increased in the patients with CRSwNP, compared to the normal values (301.43 ± 516.54 IU/ml, p = 0.033). Among the patients with CRSwNP, 12/60 (20%) had aspirin intolerance and 44/60 (73.3%) had asthma. IgE was also higher in asthmatics than non-asthmatics patients (364.9 ± 586.6 vs. 126.7 ± 135.7, respectively, p = 0.015). Patients with aspirin intolerance had higher levels of IFN-γ (4.7 ± 1.4 vs. 4.1 ± 0.6, respectively, p = 0.022). Conclusions IL-13 with high level of total IgE was observed in the patients with CRSwNP, which predisposes them to have concomitant asthma. IFN-γ seems to be down-regulated in the patients with CRSwNP, but could be over-expressed in the presence of aspirin intolerance.

Background Primary antibody deficiencies (PADs) are a heterogeneous group of disorders, characterised by increased susceptibility to recurrent bacterial infections. Common variable immunodeficiency (CVID) is the most important PAD from the clinical point of view and selective IgA deficiency (IgAD) is the most common PAD. However, the underlying gene defect in both is still unknown. As a recent study in Europe showed an association between a single nucleotide polymorphism (SNP) of AICDA gene with PADs, this study was performed to evaluate such an association in Iranian patients. Methods Fifty-eight patients with PAD, including 39 CVID and 19 IgAD, as well as 34 healthy volunteers, were enrolled in this study. Genotyping was done in all groups for an intronic SNP in AICDA (rs2580874), using real-time PCR genotyping assay. Results The less frequent genotype of AICDA in IgAD patients was AA, seen in 10.5% of the patients, which was much lower than the 30.8% in CVID patients and 38.2% in the controls. However, these differences were not significant. Indeed the GG genotype in the patients with PADs was seen in 20.7%, compared to 8.8% in the controls without any significant difference. Conclusions There was no significant association between the previously reported genetic variant of AICDA gene and the development of CVID or IgAD, but further multi-center studies are also needed.

Primary immunodeficiency disorders (PID) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections and increased susceptibility to malignancies, lymphoproliferative and autoimmune conditions. National registries of PID disorders provide epidemiological data and increase the awareness of medical personnel as well as health care providers.This study presents the demographic data and clinical manifestations of Iranian PID patients who were diagnosed from March 2006 till the March of 2013 and were registered in Iranian PID Registry (IPIDR) after its second report of 2006.A total number of 731 new PID patients (455 male and 276 female) from 14 medical centers were enrolled in the current study. Predominantly antibody deficiencies were the most common subcategory of PID (32.3 %) and were followed by combined immunodeficiencies (22.3 %), congenital defects of phagocyte number, function, or both (17.4 %), well-defined syndromes with immunodeficiency (17.2 %), autoinflammatory disorders (5.2 %), diseases of immune dysregulation (2.6 %), defects in innate immunity (1.6 %), and complement deficiencies (1.4 %). Severe combined immunodeficiency was the most common disorder (21.1 %). Other prevalent disorders were common variable immunodeficiency (14.9 %), hyper IgE syndrome (7.7 %), and selective IgA deficiency (7.5 %).Registration of Iranian PID patients increased the awareness of medical community of Iran and developed diagnostic and therapeutic techniques across more parts of the country. Further efforts must be taken by increasing the coverage of IPIDR via electronically registration and gradual referral system in order to provide better estimation of PID in Iran and reduce the number of undiagnosed cases.

Background Recently it has been suggested that, the worldwide increase in allergic diseases such as asthma, allergic rhinitis and food allergy is associated with low vitamin D intake. Objective This study measured the vitamin D levels in patients with allergic rhinitis and compared the results with the general population. Methods Vitamin D levels were assessed in 50 patients with allergic rhinitis diagnosed clinically by Allergic Rhinitis and its Impact on Asthma 2008 criteria and the result of skin prick test for aeroallergens. There was no control group, and the study results were compared with the results of another study evaluating vitamin D status in the 5,329 people of normal population of Iran. Results The prevalence of severe vitamin D deficiency was significantly higher in patients with allergic rhinitis than the normal population, 30% and 5.1% respectively (p = 0.03). Also women with allergic rhinitis had lower vitamin D levels. Conclusion Measuring vitamin D serum levels could be helpful in the routine assessment of patients with allergic rhinitis in Iran.

PROBLEM:Primary Immunodeficiency Disorders (PiD) are a heterogeneous group of genetic disorders, with different modes of inheritance. This study was accomplished in order to determine the frequency of consanguineous marriages in the families of patients with PiD. METHOD:In this study, the records 515 Iranian PiD patients were reviewed during a 25-year period. RESULTS:The mean proportion of consanguineous marriages was 65.6% among PiD patients, while the overall rate was 38.6% in the country. The rate of consanguinity was 77.8% in cellular immunodeficiencies, 75.8% in combined immunodeficiencies, 72.5% in defects of phagocytic function, 58.6% in other immunodefiiencies, 54.1% in predominantly antibody deficiencies, and 50% in complement deficiencies. Moreover all patients with immunodeficiency associated with other diseases had consanguineous parents. Such marriages were most common in the parents of patients with Chediak-Higashi syndrome, severe combined immunodeficiencies, primary CD4 deficiency, ataxia-telangiectasia, selective IgG class deficiencies, chronic granulomatous disease, and Schwachman syndrome. CONCLUSIONS:It is important to inform the general population about the dangers of consanguinity, which is very common in some areas such as Iran. Premarital examination to avoid genetic diseases could be suggested, especially in a community where the rate of consanguineous marriage is high.

Epidemiological studies have shown wide geographical and racial variation in the prevalence and patterns of immunodeficiency disorders. To determine the frequency of primary immunodeficiencies (PID) in Iran, the Iranian Primary Immunodeficiency Registry (IPIDR) was organized in 1999. We extracted the patient's data, by using a uniform questionnaire from their hospital records. The diagnosis of patients was based on WHO criteria. By now, 440 patients with PID, who were observed during a period of 20 years, have been registered in our registry. Among these patients, the following frequencies were found: predominantly antibody deficiency in 45.9% of patients (n = 202), phagocytic disorders in 29.09% (n = 128), T-cell disorders in 24.31% (n = 107), and complement deficiencies in 0.68% (n = 3). Common variable immunodeficiency was the most frequent disorder (n = 98), followed by chronic granulomatous disease (n = 86), ataxia telangiectasia (n = 48), x-linked agammaglobulinemia (n = 45), selective IgA deficiency (n = 42), combined immunodeficiency (n = 15), and severe combined immunodeficiency (n = 14). This study revealed that antibody deficiencies is the most frequently diagnosed primary immunodeficiency disorder in our patients, which is similar to that observed in other registries. A comparative study shows some differences between our results and other registries.

Background CD4+ CD25+ T-regulatory (Treg) cells play critical roles in maintaining peripheral tolerance and preventing autoimmunity. As characteristics of Treg cells have not been precisely investigated in chronic urticaria (CU) yet, this study was performed. Objective To determine the frequencies of circulating CD4+ CD25+ FOXP3+ T cells and serum levels of interleukin (IL)-10, transforming growth factor (TGF)-β, and IL-17 in patients with chronic autoimmune urticaria and chronic idiopathic urticaria compared to healthy controls. Methods Peripheral blood mononuclear cells (PBMCs) were obtained from patients with CU and healthy controls. The frequency of CD4+ CD25+ T cells in PBMCs and expression levels of FOXP3 were detected by flow cytometry. The serum levels of IL-10, TGF-β, and IL-17 were measured by enzyme-linked immunosorbent assay. Results A significant decrease in the percentage of circulating CD4+ CD25+ FOXP3+ T cells was detected in patients with CU, compared to control subjects. However, no significant difference was detected on the serum levels of IL-10, TGF-β, and IL-17 between patients with CU and control subjects. Conclusions This study demonstrated that the frequency of Treg cells in PBMCs was decreased in patients with CU. Further studies are needed to clarify the exact role of Treg cells in the pathogenesis of CU and factors regulating their function.

Background Aspirin-exacerbated respiratory disease (AERD) is a syndrome frequently seen in patients with chronic rhinosinusitis and nasal polyposis (CRSwNP). However, there are few studies on evaluating the prevalence of aspirin (acetylsalicylic acid [ASA]) hypersensitivity in patients with CRSwNP using the oral aspirin challenge (OAC) test. This cross-sectional study was designed to determine the frequency of ASA hypersensitivity and factors associated with it in patients with CRSwNP in Tehran, Iran. Methods Adult patients with CRSwNP who were presented to the asthma and allergy clinic were recruited for the study. After confirming CRS and NP, OAC was performed to evaluate/confirm the diagnosis of ASA hypersensitivity. Atopic evaluation was performed using skin-prick test, nasal smear, blood eosinophil count, and serum total IgE. Results Eighty Iranian patients (43 women and 37 men) with CRSwNP were enrolled (mean age, 38.9 ± 10.7 years). OAC was performed in all of the patients and 39 patients (48.8%) had a positive reaction; among them, 14 (35.8%) had a self-reported history of ASA hypersensitivity. Concomitant asthma, previous polyp surgery, high polyp score, and ASA hypersensitivity history were all associated with positive OAC (p < 0.05). Presence of AERD was not associated with age, stage of asthma, blood eosinophilia, nasal smear eosinophilia, and atopy. Conclusion ASA hypersensitivity is common in patients with CRSwNP in Tehran, Iran. Patients at risk for AERD should be evaluated for the presence of ASA hypersensitivity with ASA provocation challenge test to confirm the diagnosis.

Pediatric patients with leukocyte adhesion deficiency type-I (LAD-I) experience severe and recurrent life-threatening bacterial infections with failure of pus formation and delayed wound healing. LAD-I is a rare inherited disease caused by mutation in the leukocyte CD18 integrin expression, resulting in defective adherence and migration of leukocytes, in particular neutrophilic granulocytes through the intravascular space. Hematopoietic SCT is the only curative treatment option available to patients with LAD-I. Since 2007, in a prospective trial, reduced-intensity conditioning regimen have been developed for 10 consecutive patients with LAD-I who were referred to our center. Based upon available data, it is the first time that such a number of patients affected by LAD-I have been treated with this regimen. This study attempts to show that reduced-intensity regimen leads to a favorable result in LAD-I patients even in those who have experienced comorbid complications. Following transplantation, some patients develop mixed chimerism, however, in our study mixed chimerism was not followed by transplant rejection.

In order to determine the clinical and laboratory findings of Iranian patients with presumed hyper-immunoglobulin E syndrome (HIES), the medical records of 22 patients from 21 unrelated families, who had been registered in the Iranian Primary Immunodeficiency Registry, were observed. The median age of patients at the time of first symptom and at the time of diagnosis was 1 month and 52.5 months, respectively, with a median diagnosis delay of 70 months. 13 families had consanguineous marriages. IgE level was higher than 2000 IU/ml in all patients, ranging from >2000 to 80,000 IU/ml. The most commonly occurring manifestations were: eczema and dermatitis, pneumonia, upper respiratory tract infections, cutaneous abscesses, diarrhoea, deep abscesses, and otitis media. Other less frequent manifestations were: mucocutaneous candidiasis, sinusitis, cutaneous ulcers, Molluscum contagiosum, herpetic keratitis, onychomycosis, conjunctivitis, septic arthritis, and meningitis. Five patients were complicated by bronchiectasis due to recurrent pneumonia and 5 patients died because of severe infections and malignancy. The HIES is a multisystem disorder that affects especially cutaneous, respiratory, skeletal and the immune system. Although HIES is a rare condition, the recurrent infections should always raise a suspicion, which deserves further evaluation for detecting the syndrome.

Primary immunodeficiency disorders (PID) are a heterogeneous group of diseases, characterized by an increased susceptibility to infections. A total of 930 patients (573 males and 357 females) are registered in Iranian PID Registry (IPIDR) during three decades. Predominantly antibody deficiencies were the most common (38.4%), followed by congenital defects of phagocyte number and/or function (28.3%), other well-defined immunodeficiency syndromes (17.7%), combined T- and B-cell immunodeficiencies (11.0%), complement deficiencies (2.4%), and diseases of immune dysregulation (2.3%). Common variable immunodeficiency was the most frequent disorder (20.8%), followed by chronic granulomatous disease, ataxia-telangiectasia, btk deficiency, selective IgA deficiency, and T-B-severe combined immunodeficiency. The frequency of other PID disorders was less than 50 in number (