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Abstract Background The poly-sensitization to Hymenoptera venom makes it difficult to select genuine allergens for immunotherapy and increases patients’ costs. The objective of this study was to determine the culprit allergen in dual or triple-sensitized patients to three Hymenoptera venoms through molecular diagnosis and evaluating the results of incorporating the molecular diagnosis with skin tests. Methods Thirty-two patients with anaphylactic reactions and dual or triple-sensitization to Hymenoptera venoms in skin tests entered this study. IgE-sensitization to whole extracts and molecules of Apis mellifera (Api m), Vespula vulgaris (Ves v), and Polistes dominulus (Pol d) was evaluated utilizing ALEX or ImmunoCAP. Results Twenty-nine patients (90.6%) were male. IgE-sensitization to at least one of the allergenic molecules related to Apis mellifera, Vespula vulgaris, and Polistes dominulus was seen in 59.4, 53.1, and 21.9%, respectively. Among 32 patients, 14 (43.8) and 8 (25%), were mono-sensitized to Api m and Ves v components in ALEX, respectively. Double sensitization to Hymenoptera was identified in 18.8% of patients in ALEX. Api m 1+/Api m 2−/Api m 10− and Ves v 1+/Ves v 5+ demonstrated the most prevalent sensitizations patterns in our patients. Conclusions The molecular diagnosis of IgE-sensitization to Hymenoptera venoms can be valuable, especially in patients who show dual or triple-sensitization in skin tests, as the ALEX results revealed mono and double-sensitization to Hymenoptera venoms in 22 and 6 patients, respectively. Regarding the high cost and adverse reactions of venom immunotherapy, especially for two or three venoms, incorporating the molecular diagnosis alongside skin tests for accurate diagnosis of the culprit venom could help decrease costs for patients.

Abstract Background Chronic Rhinosinusitis (CRS) is a paranasal sinus inflammatory disease and is divided into two subgroups defined as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays a T helper (Th)2 biased phenotype, and based on sensitivity or tolerance to aspirin or non-steroidal anti-inflammatory drugs (NSAID), is further subdivided into Aspirin-exacerbated respiratory disease (AERD) and non-AERD groups. Considering the challenge of diagnosis and treatment in patients with CRSwNP, particularly the AERD subtype, and the significance of endotyping in these patients, we examined the immune profile and endotyping based on gene expression analysis in the AERD and the non-AERD groups of patients with CRSwNP. Material and method In this study, 21 patients were enrolled and were categorized into AERD (N = 10) and non-AERD (N = 11) groups based on their sensitivity to aspirin. After the special washing period, nasal polyps were biopsied in both groups, and the infiltration of eosinophils, neutrophils, plasma cells, and lymphocytes was compared between the AERD and the non-AERD groups. Also, gene expression levels of transcription factors including Tbet, GATA3, RoRγt, and FoxP3 and inflammatory cytokines including interleukin (IL)1β, IL1RAP (IL1 receptor accessory protein), IL2, IL4, IL5, IL10, IL13, IL17, TNFα, and IFNγ were investigated by quantitative Real-time PCR (qRT-PCR). Statistical analyses were performed using analytical tests including Kolmogorov–Smirnov, Mann-Whitney, and T-test. A P value less than 0.05 was considered statistically significant. Results The mean ± SD age of the studied groups was 37 ± 8.7 years old (21–50) for the AERD, and 40.4 ± 7.7 years old (31–52) for the non-AERD. LMS/EPOS/SNOT scores and pulmonary function tests showed no difference between the two groups. Serum immunoglobulin E (IgE) levels were found to be higher in patients with AERD (p = 0.04), however, the peripheral blood counts of eosinophils were comparable in the two groups. In the histopathologic analysis, the AERD group showed higher percentages of eosinophils (p = 0.04), neutrophils (p = 0.04), and plasma cells (p = 0.04) than the non-AERD group. Additionally, the gene expression levels of GATA3 (p = 0.001), IL4 (p = 0.04), IL5 (p = 0.007), and IL17 (p = 0.03) were significantly higher in the AERD than the non-AERD groups. Conclusion Higher gene expression levels of GATA3, IL4, IL5, and IL17 were observed in the AERD group compared with the non-AERD group. These findings point to distinct patterns of inflammation in patients with AERD, with a predominance of Th2 inflammation.

Abstract Genetic defects in the development, maturation, and/or function of the immune cells can lead to Inborn errors of immunity (IEI) which may predispose patients to malignancies. The overall risk for cancer in children with IEI ranges from 4 to 25% and the type of malignancy is highly dependent on the specific mutant gene underlying IEI. We investigated 3056 IEI patients registered in the Iranian national registry between the years 1999 and 2020 in this retrospective cohort study. The frequency of malignancy and its association with the type of IEI in these patients were evaluated. A total of 82 IEI patients with malignancy were enrolled in this study. Among them, predominantly lymphoma was the most common type of malignancy (67.1%), followed by leukemia (11%), and cancers of the head and neck (7.3%). Among identified lymphoma cancers, non-Hodgkin’s lymphomas were the most frequent type (43.9%) followed by different subtypes of Hodgkin’s lymphoma (23.2%). Solid tumors (18.3%) appeared to be very heterogeneous by type and localization. The correlation between the type of malignancy and survival status and the association between the type of malignancy and IEI entities were unremarkable. The awareness of the association between the presence of IEI and cancer highlights the importance of a synergistic effort by oncologists and immunologists in the early diagnosis of malignancy and personalized therapeutic strategies in IEI patients.

Abstract Background Progressive multifocal leukoencephalopathy is a rare demyelinating disease that is often secondary to lytic destruction of oligodendrocytes and, to a lesser extent, to astrocytes’ response to human neurotrophic John Cunningham polyomavirus. Any underlying congenital disorder of primary or secondary immunodeficiency may predispose to virus infection and possible invasion of the brain. We present the first reported case of progressive multifocal leukoencephalopathy due to a mutation in the RAC2 gene. Case presentation We describe the case of a 34-year-old Iranian man with recurrent infections from the age of 2 years, along with other disorders such as nephritic syndrome, factor XI deficiency, and hypogammaglobulinemia. He was treated regularly with intravenous immunoglobulin from the age of 10 years with a diagnosis of common variable immune deficiency. Genetic testing confirmed a novel homozygous mutation in the RAC2 gene in the patient. Owing to the onset of neurological symptoms a few months ago, the patient was completely avaluated, which confirmed the diagnosis of PML. Despite all efforts, the patient died shortly after progression of neurological symptoms. Conclusions According to previous studies, progressive multifocal leukoencephalopathy has been associated with 26 cases of primary immunodeficiency. Our patient presents a new case of primary immunodeficiency with progressive multifocal leukoencephalopathy. Accurate examination of these cases can help us to gain insight into the immune response to John Cunningham virus and better treat this potentially deadly disease.

Coronavirus disease 2019 (COVID-19) affects millions of people worldwide. Clinical manifestations range from asymptomatic to severe viral pneumonia. CVID patients with COVID-19 infection are not adequately studied. In some studies, CVID patients had higher mortality rates, although other studies showed that CVID patients might have an uncomplicated COVID-19 infection. We describe 14 cases of COVID-19 infection in Iranian CVID patients in this study, including clinical manifestations, laboratory findings, and treatment strategies. There were 29% of patients with mild disease, 43% with moderate disease, and 29% with severe disease in this study. A critical case and a death occurred in none of our patients. There were six cases of infection more than two weeks after receiving the second dose of Sinopharm BIBP COVID-19 vaccine; all had mild to moderate disease. Among these patients, Remdesivir was the most frequently prescribed medication. According to this study, most of our patients presented with an uncomplicated disease course.

Immunoglobulin G4-Related Disease (IgG4-RD) is a systemic fibro-inflammatory disease that has been proposed as a separate entity since thebeginning of this century. The disease is often manifested by increasedserum IgG4 levels and certain histopathological manifestations. The patientmentioned in this article is a 29-year-old man from Tajikistan, who has had achronic cough since the beginning of 2018 without a previous history of thedisease. At first, he was diagnosed with pneumonia for a long time and thenunderwent a lung biopsy due to exacerbation of symptoms and the spreadof lung lesions in radiology but no abnormalities were found in theseevaluations. The patient traveled to Iran to continue his treatment. He wasre-evaluated and then the previous samples taken from the patient's lungtissue were re-examined. There were key findings in favor of diagnosingIgG4 RD. Evaluations did not confirm the involvement of other organs. Hewas first treated with steroids and due to recurrence of symptoms, he wastreated with rituximab once which was significantly effective in improving thepatient's clinical symptoms. In general, it can be concluded that thediagnosis of IgG4-RD is very challenging and if it has not been diagnosedand treated in time, it can lead to irreversible fibrosis and permanent loss offunction of the involved organ.

Type 2 Griscelli syndrome (Type2 GS) is a primary inborn error of the immune system, classified in the immune dysregulation group.1,2 There are three different types of the disease, with different genetic causes responsible for the autosomal recessive inheritance pattern. Although hypopigmentation is common in all variants, neurological involvement or immunodeficiency with varying severity is seen in different types. Molecular motor protein myosin 5 an (MYo5A) [Type1GS], guanosine Triphosphate (GTP) binding protein (RAB27A) [Type2GS], and mutation in human melanophilin (MLPH) [Type 3GS] which is limited to hypopigmentation are reported as the known genetic defects in GS.3 Severe, ineffective, and uncontrolled inflammatory reactions are referred to as the pathogenesis of Hemophagocytic lymphohistiocytosis (HLH). HLH is a life-threatening condition that can be defined as either primary or secondary. Secondary causes happen in the context of autoimmunity, malignancy, spontaneous, or infections.4 Prenatal infections play an important role in causing long-term complications in the fetus. Some of them include toxoplasmosis, rubella, cytomegalovirus, herpes simplex, and other organisms including syphilis, parvovirus, and Varicella zoster, known as TORCH syndrome (5).TORCH has been well described for a long time but there are limited reports of developing HLH in the context of prenatal infections. We described a type 2GS syndrome with neonatal-onset HLH triggered by a prenatal infection.

Increased susceptibility to autoimmunity, malignancy, and allergy in addition to recurrent infections are the main characteristics suggesting for the primary immunodeficiency diseases (PID). CTLA-4 is predominantly expressed on activated and regulatory T-cells, which can bind to CD80/CD86 molecules on antigen-presenting cells as a negative regulator. Here, we describe a 24-year-old male born from consanguineous parents with heterozygous CTLA-4 mutation who presented with multiple autoimmune diseases. His past clinical history revealed alopecia areata atfour years old and subsequently, he developed Evans syndrome, type 1 diabetes mellitus, hypothyroidism, and chronic diarrhea while chronic rhinosinusitis and cytomegalovirus (CMV) colitis were the only infectious manifestations. Immunologic investigations revealed: low B cell count, abnormal Lymphocyte transformation test (LTT) to phytohemagglutinin (PHA), and hypogammaglobulinemia. Although all available treatments such as Intravenous Immunoglobulin (IVIG) therapy, immunosuppressive drugs, and antibiotic therapy were applied, diarrhea was not controlled due to colitis, which remained challenging. Whole exome sequencing was performed and the result showed heterozygous variant CHR2.204,735,635 G>A in the CTLA-4 gene, which was confirmed by the Sanger method. CTLA4 haploinsufficiency leads to autoimmune disorders, recurrent respiratory infections, hypogammaglobulinemia, lymphoproliferation with organ infiltration, and lymphocytic interstitial lung disease.

Introduction: One of the most effective ways to improve the management of asthma in primary care is using guidelines in the patient management process; but due to lack of time, their use is very limited. One way to solve this problem is mechanized guideline in a form of decision-support system that requires computer-interpreted guideline (CIG). In this study, a CIG was developed for asthma management in primary care. Methods: This qualitative study was performed using mini-Delphi method uses a workflow-based approach to develop a CIG. The workflows and data components were extracted through Business Process Model and Notation (BPMN) language and Enterprise Architecture (EA) software. Afterwards, they were confirmed through an expert panel of five asthma specialists. Results: The developed CIG included three major workflows, four sub-workflows, and 21 data components. Main workflows included treatment, drug interaction, and follow-up time. Sub-workflows were related to treatment workflow that were developed based on the patient visit number and age. Conclusion: Because the accuracy of this workflow was confirmed by asthma specialists, it is expected that the design of this CIG will lead to development of a cost-effective software for the management of asthma and better detection of drug interactions.

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,

Severe Combined Immunodeficiency (SCID), characterized by a profound decrease in both the number and function of T cells, is related to more than 20 different mutations. Recombination-activating gene (RAG) 1 and 2 seem to be two of the most common forms presenting with various manifestations, including typical SCID, Omenn syndrome (OS), atypical SCID (AS), or delayed onset combined immunodeficiency with granulomas. One interesting manifestation in RAG mutation is the change in the immunophenotype over time, even after hematopoietic stem cell transplantation (HSCT). As bone marrow transplantation (BMT) is the only curative treatment of SCID, it is necessary to differentiate between SCID and OS due to the different conditioning regimens (CR). We present a novel case of atypical SCID (SCID manifestations with more than 300 CD3+T cells) caused by RAG 2 gene mutation whose immunophenotype changed to atypical Omenn syndrome (all Omenn syndrome manifestations except rash, eosinophilia, and elevated IgE) over time.Differentiation of leaky SCID, SCID and Omenn syndrome in RAG mutation genes and overlap manifestations is important in treatment plan and prognosis.

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

Abstract 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).

Asthmatic patients may have aspirin-exacerbated respiratory disease and experience acute dyspnea and nasal symptoms within 3 hours after the ingestion of aspirin. This study aimed to evaluate the effect and outcome of daily low-dose aspirin in the treatment of moderate to severe asthma in patients with concomitant aspirin hypersensitivity and chronic rhinosinusitis with nasal polyposis (CRSwNP). This clinical trial was conducted from February 2014 to February 2015 on 46 adult patients with moderate to severe asthma accompanied by CRSwNP. Patients with a positive aspirin challenge were blindly randomized in three groups receiving placebo/day (A); aspirin 100 mg/day (B); and aspirin 325mg/day (C), respectively. Clinical findings, FEV1 and ACT scores were recorded and compared before, during, and after treatment for 6 months. Of 46 participants at baseline, 30 patients completed this 6-month trial study. The level of asthma control was significant; based on Asthma Control Test (ACT) when comparing the results in groups A and C and also groups B and C, but it was not significant when comparing ACT scores between groups A and B. FEV1 before and after treatment was significant when comparing groups A and B, groups A and C, and groups B and C. To conclude, aspirin desensitization with a daily dose of 325 mg aspirin resulted in the improvement of long-term control of asthma. A daily aspirin dose of 100 mg was not associated with such an increase in ACT score.

Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare primary immunodeficiency disorder characterized by recurrent infections and low immunoglobulin levels due to variable combined immunodeficiency, and centromeric region instability, and facial dysmorphism. We describe a 12-year-old boy with recurrent respiratory tract infections, facial anomalies, scoliosis, and psychomotor retardation. He had recurrent pneumonia with low serum IgG and IgM levels during infancy and preschool age. Later at the age of 10, he developed recurrent ear infections. An IgA and IgM deficiency was found accompanied by a normal B-cell and T-cell count as well as an impaired candida-induced T-cell proliferation. Further evaluations revealed a missense mutation in the DNMT3B gene on chromosome 20. Chromosomal analysis showed a sunburst multi-radial feature on chromosome 1, which is a hallmark of ICF syndrome. The genetic mutation and chromosomal abnormality along with clinical findings are compatible with the diagnosis of ICF syndrome. To the best of our knowledge, this is the first time that scoliosis is observed in an ICF patient. The additional variable clinical symptoms in the case were the presence of spastic gait as well as hypogammaglobulinemia with immunoglobulin isotype switch at different ages.

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/corticosteroid or adrenaline. 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.

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 non-steroidal 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 pre-bronchodilator 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.

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.

Introduction:To evaluate the role of allergic-type and infectious-type cytokines in children with chronic otitis media with effusion (OME) Materials and Methods:We investigated serum levels of interleukins (IL)-4, IL-5, and IL-13, along with interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), by enzyme-linked immunosorbent assay (ELISA) in 35 children with OME and 28 healthy controls. Results:Children with OME had significantly higher levels of IL-5 in comparison with the control group, ranging from 1 pg/ml in cases to 0.04 pg/ml in controls (P=0.009). However, after adjusting for confounding variables, there was no significant difference in serum levels of IL-13, IL-4, IFN-γ, or TNF-α between the two groups (P=0.287, P=0.627, P=0.793, and P=0.217, respectively) Conclusions:The findings of this study suggest that in comparison with the control group, serum IL-5 levels were elevated in OME cases.

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.

Despite the increasing prevalence of anaphylaxis, there is little information about the characteristics and practice of healthcare providers in treating anaphylaxis, so this study was conducted to record the characteristics and therapeutic approaches of anaphylaxis from May 2012 until April 2015, the data of all patients diagnosed with anaphylaxis in the Allergy department of three referral university hospitals in Tehran, Iran were recorded. Thereafter, the demographics, clinical features, triggers and therapeutic approach were evaluated. This study investigated 136 individuals, 64 males (47%) between 6 months and 68 years old, as well as 72 others (52.94%) under 18 years of age (pediatric). The following were the most common organs involved: Skin 86.02% (pediatric 91.66% vs adult 79.68%), respiratory tract 51.47% (pediatric 43.05% vs adult 60.93%), cardiovascular 50.73% (pediatric 54.16% vs adult 46.87%), gastrointestinal 20.58% (pediatric 27.7% vs adult 12.5% ) and neurologic system 5.88% (only in adults). The following were the most identified causing foods 69 (50.37%)[42 pediatric (children) and 27 adults], drugs 34( 25%)[14 pediatric and 20 adults], idiopathic 16( 11.77%)[3 pediatric and 13 adults], insect sting 7( 5.15%)[3 pediatric and 4 adults] , exercise 6( 4.42%) [1 pediatric and 5 adults]. Milk, egg and wheat were the most common causative foods in pediatric cases but sesame, as well as egg and milk were the most common causes in adults. Epinephrine injection, auto injector epinephrine prescription as a discharging plan and referral to an allergist were: 10.78, 1.96 and 7.8 %, respectively. In this case series we found that, cutaneous, respiratory, cardiovascular and gastrointestinal complains were the most common manifestations and food, drug and idiopathic were the most common causes.In this study, the diagnosis of anaphylaxis, epinephrine subscription and referral to an allergist were significantly lower in comparison to other studies.

Cow’s milk allergy (CMA) is the most frequent food allergy in children and oral immunotherapy (OIT) is a promising approach for treatment of patients. The most challenging cases are anaphylactic with coexisting asthma and proposing safe protocols is crucial especially in high risk groups. Considering that CMA varies among patients, an individualized OIT protocol would be beneficial to achieve a safer and more efficient method of desensitization. 18 children more than 3 years of age with IgE-mediated CMA were enrolled. CMA was confirmed by positive skin prick test (SPT) and positive oral food challenge (OFC) and 60% of individuals had a convincing history of persistent asthma. SPT with milk extracts, whole fresh milk and serially diluted milk concentrations were performed. The dilution of milk that induced 3-5 mm of wheal in each individual was selected as the starting dilution for OIT. Desensitization began by 1 drop of the defined dilution and continued increasingly. Overall, 16 out of 18 children (88.8%) achieved the daily intake of 120 mL of milk. Four out of these 16 children accomplished the protocol without any adverse allergic reactions. 12 patients experienced mild to severe reactions. Wheal and erythema in SPT (p≤0.001), and sIgE (p≤0.003) to most milk allergens were significantly decreased following desensitization. We successfully desensitized 16 of 18 children with IgE-mediated CMA by individualized desensitization protocol. Individualizing the OIT protocol would be helpful to save time and perhaps to relieve the allergic symptoms after ingesting cow’s milk intake.

LPS-Responsive Beige-like Anchor (LRBA) deficiency is a disease which has recently been described in a group of patients with common variable immunodeficiency (CVID) in association with autoimmunity and/or inflammatory bowel disease (IBD)-like phenotype. We here describe a 10-year-old boy who experienced recurrent infections, mainly in the respiratory system, associated with thrombocytopenia and anemia. Immunological workup showed low numbers of B cells and low IgG, but normal IgM levels. In spite of therapeutic doses of antibiotics, antivirals, and antifungal agents, in addition to immunoglobulin replacement therapy, he developed disseminated involvement of both lungs with peripheral nodules; transbronchial lung biopsy revealed possible bronchiolitis obliterans organizing pneumonia (BOOP). Combined homozygosity mapping and exome sequencing identified a homozygous LRBA mutation in this patient (p.Asp248Glufs*2). Such clinical and immunological findings have not been described to date and illustrate the broad and variable clinical phenotype of human LRBA deficiency.

Objective(s): According to the occupationally risk of infection in staff workers who have direct contact with mycobacterium species, we investigated their immunological parameters and compared with healthy purified protein derivative (PPD) negative volunteers. Materials and Methods : We investigated 20 PPD positive volunteers working at Tuberculin Unit of Razi Vaccine and Serum Research Institute and PPD negative healthy controls with no exposure or history of active tuberculosis. The percentages of circulating lymphocyte subpopulations were detected by flowcytometry. IL-4 and IFN-γ production levels were measured by ELISA in supernatants of PPD-stimulated peripheral blood mononuclear cells (PBMCs) culture. Results : Tuberculin workers showed an increase in IFN-γ level and significant decrease of CD4+ T cells percentage and CD4/CD8 ratio compared to PPD negative normal individuals. However the IL-4 production and percentage of other lymphocyte population has been unchanged. Discussion: These observations suggest that the immunological parameters of tuberculin workers with PPD positive reaction, who are occupationally exposed to mycobacterium antigens, could be changed. Future studies will be directed towards cytokine networking and regulatory lymphocytes, which will help us validate the significant data presented in this study.

ABSTRACT Food allergy is estimated about 8% in children. The relationship between food and manifestation of allergy symptoms and its confirmation for accurate diagnosis is very important. Allergic rhinitis is a common disease with a prevalence of 40% among different societies. The prevalence of food-induced allergic rhinitis appears to be less than 1 percent. Food reactions often lead to rhinitis symptoms at a no immunologic nature. Although the role of food and fruits in developing allergic rhinitis is not clearly identified, in a very small percentage of patients, rhinitis is the clinical manifestation of food allergy.

The Link between allergic rhinitis and asthma is well known. Bronchial hyperreactivity (BHR) may be present in rhinitis. The present study was aimed to compare airway responses in patients with rhinitis symptoms alone following exercise challenge, and to determine relationship of two different respiratory function tests. 98 subjects with rhinitis were investigated by spirometry and impulse oscillometry before and after exercise challenge. No significant difference was detected between spirometry and impulse oscillometry measurements before and after exercise challenge in subjects with rhinitis alone. No correlation between spirometry and impulse oscillometry indices was found in pre and post- exercise stages. We therefore conclude that exercise challenge is not an appropriate test to determine airway hyperresponsive in subjects with rhinitis symptoms alone and findings of spirometry and impulse oscillometry are not interrelated.

Allergic Rhinitis (AR) is one of the most common chronic diseases in the developed countries. This study was performed to investigate the effect of CpG-ODN in alteration of T-helper (Th)1/Th2 balance of patients with AR treated with intranasal corticosteroids (INCs) and antihistamines. Peripheral blood mononuclear cells (PBMCs) of 20 patients with AR were isolated before and after 45 days therapy. Cytokine production (IL-4, IL-10, IL-13, IFN-γ) and specific Ch.a IgE in response to CpG co- administration of natural chenopodium album (CpG/Ch.a) or recombinant Ch.a (CpG/rCh.a) allergen were investigated in supernatants.of cultured PBMCs using ELISA Intracellular IL-10 was also assessed in CD4+ cells using flow cytometry. Significant increase in production of IFN-γ and IL-10 and decrease in production of IL-4 were found in supernatants of cultured PBMCs activated with CPG/ch.a and CPG/rch.a. of both CpG/Ch.a and CpG/rCh.a compared to allergens alone, before and after therapy. After therapy, IFN-γ production with CpG/Ch.a was significantly increased in comparison with before (237 vs. 44 pg/ml, p=0.001). IFN-γ and IL-10 production with CpG/rCh.a was significantly increased after therapy compared to before (407.6 vs. 109 pg/ml, p=0.01 for IFN-γ; 171.7 vs. 52.6 pg/ml, p=0.008 for IL-10), whilst IL-4 was significantly decreased (2.1 vs. 5.8 pg/ml, p=0.02). Intracellular IL-10 expression was also significantly increased in response to either CpG/Ch.a or CpG/rCh.a that showed intracellular assay could be more sensitive than ELISA. Also, treatment with intranasal corticosteroids and antihistamines could enhance this CpG effect, in vitro.

Patients with allergic rhinitis (AR) show increased production of the Th2-related cytokines. Almost always, intranasal corticosteroid (INC) and antihistamine are used as routine therapy of AR. This study was performed to determine the in vitro secretion of cytokines profiles of PBMCs in patients with AR sensitive to Chenopodium album (Ch.a) pollens before and after treatment with INC (Fluticasone propionate) and oral antihistamine (Loratadine). PBMCs of 20 patients with AR, were tested in vitro for cytokine production. These cells were stimulated with natural or recombinant Ch.a. The levels of IL-4, IL-13 and IFN-, were measured in supernatants of cultured cell 96h after stimulation using ELISA. The PBMCs of 20 normal individuals were also similarly treared for comparison of results. The production of IL-4 by the patients' cells stimulated with either Ch.a or rCh.a was significantly higher than normal levels before therapy (p=0.04 and p=0.02, respectively). After therapy, a significant decrease in production of IL-4 and a significant increase in production of IL-10 were found in PBMCs stimulated with natural Ch.a, in comparison to the results before stimulation (p=0.03 for IL-4; p=0.04 for IL-10). Similarly, these results were seen in the production of IL-4 and IL-10 stimulated with rCh.a allergen after therapy in comparison to the results before stimulation (p=0.01 for IL-4; p=0.03 for IL-10). This study suggests INC (Fluticasone propionate) and oral antihistamine (Loratadine) have the capacity to inhibit the production of IL-4 and shift Th2/Th1 responses, probably due to increase the level of immunoregulatory IL-10. Therefore, it could be concluded that therapy with INC and antihistamine has pharmacologic and immunologic therapeutic effects on AR patients.

Macular or maculopapular skin reactions are frequent events in skin allergies as well as in viral infections. Clinically, the differentiation may be difficult in the absence of a clear relationship with drug intake or in the failure to detect measles virus-specific antibodies. Studies on drug-specific T cell lines and T cell clones isolated from skin-allergy patients have suggested that these cells may represent a significant source of IL-4 and IL-5. On the other hand, viral infections are frequently associated with elevated IFN-γ levels. Determination of serum cytokine levels helps to differentiate between skin allergies and virally induced skin eruptions. Forty patients suffering from skin allergy and 40 patients with measles infection entered the study. Serum IL-4, IL-5 and IFN-γ levels were determined by ELISA assay for skin-allergy and measles patients. In 37/40 patients with skin allergy, IL-4 was elevated and in 6/40 patients with skin allergy IFN-γ was measurable. In 29/40 patients with measles infection, IFN-γ serum levels were elevated and 32/40 patients with measles had elevated IL-4 levels. IL-5 was increased in 32/40 patients with measles infection and in 34/40 patients with skin allergy. These data underline the distinct pathogenesis of these morphologically similar exanthemas and suggest that a combined analysis of IL-4, IL-5, and IFN-γ might help differentiate skin eruptions.

Chronic Granulomatous Disease (CGD) represents a group of inherited disorders of phagocytic system, manifesting recurrent infections at different sites. The present study was accomplished in order to determine the gastrointestinal manifestations of CGD patients. Fifty-seven patients (38 males and 19 females) with CGD, who had been referred to three immunodeficiency referral centers in Iran, were studied during a 24-year period (1980-2004). The median age at the time of study was 14.5 years old (1-56 years). The median onset age of symptoms was 5 months (1 month – 13.75 years), and that of diagnostic age was 5 years (2 months- 54.1 years), with a diagnostic delay of 33 months, on average. Seven patients were presented with acute diarrhea, 3 with oral candidiasis, and 2 with liver abscesses as the first chief complaints. Twenty-four cases (42.1%) had been complicated by gastrointestinal manifestations during their course of the disease. Of those, 12 cases (21.1%) had diarrhea, 7 (12.3%) oral candidiasis, 5 (8.8%) hepatitis, 4 (7.0%) hepatic abscess, and 2 cases (3.5%) gastric outlet obstruction. Also, failure to thrive was detected in 6 patients (10.5%). Four patients died (7%). CGD should be excluded in any patient with gastrointestinal manifestations especially chronic diarrhea, hepatic abscess, and gastric outlet obstruction.

Primary immunodeficiencies (PID) are a group of disorders, characterized by an unusual susceptibility to infections. Delay in diagnosis results in increased morbidity and mortality in affected patients. The purpose of this study was to determine the mortality rate of Iranian immunodeficient patients referred to Children Medical Center Hospital affiliated to Tehran University of Medical Sciences over a period of 20 years. In this study, records of 235 (146 males, 89 females) patients with immunodeficiency who were diagnosed and followed in our center, during 22 years period (1979-2001) were reviewed. The diagnosis of immunodeficiency was based on the standard criteria. The cause of death was determined by review of death certificates. Antibody deficiency was the most common diagnosis made in our patients. The overall five-year survival rate was 22.7% in our studied patient group; this was greatest in antibody deficiency. During the 22 year period of study, 32 patients died. As some of the patients could not be located, the true mortality rate ranged between 13.6% and 17.5%. The main leading cause of death were lower respiratory tract involvement in 14 cases (44%). The most common pathogenic microorganisms causing fatal infections were psudomonas and staphylococcus in 9 cases (28.1%) followed by E. coli in 7 (21.9%), tuberculosis in 13 (40.6%) and salmonella in 1 (3.1%). Based on our study, delay in diagnosis in patients with PID results in tissue and organ damage and several complications. Mortality and morbidity are increased in undiagnosed patients.