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Introduction: There has been substantial increase in food allergies in recent decades. The management of severe food allergy often includes strict avoidance and medical therapies. However, oral immunotherapy (OIT) is a promising treatment option for these patients, which is still being investigated. Methods: The study recruited children from 2 years onward with a history of wheat anaphylaxis who had been referred to the Mofid Children Hospital. Wheat allergy was confirmed by a double-blind placebo-controlled food challenge. OIT was started to reach 5.28 g of wheat protein supplied in 60 g of bread. Besides immunologic measurements, a second and third oral food challenge (OFC) was performed after 3 months and 1 year of maintenance therapy to evaluate the long-term efficacy of wheat OIT (WOIT). Results: Seventeen patients completed the 3-month maintenance phase; 8 of them demonstrated negative OFCs. All of the 9 with positive OFCs were asked to continue the daily consumption of 60 g of bread for another year. Three patients with positive OFCs were followed for 1 more year and were asked to continue eating 60 g of bread every other day. The serum level of wheat sIgE was significantly increased at the end of the buildup phase (p = 0.026) and dramatically dropped at the end of the maintenance phase (p = 0.022). Conclusion: To conclude, WOIT is an effective and safe modality of treatment if it is administered under strict supervision.

Autoimmune disorders are reported as presenting signs in patients with immunoglobulin A (IgA) deficiency. Herein, we aim to evaluate serum IgA among patients with autoimmune polyendocrinopathy.Patients with two or more autoimmune endocrinopathies were selected and the serum IgA levels were measured. Patients with an isolated low serum IgA (7 mg/dL) after exclusion of other causes of hypogammaglobulinemia were considered as selective IgA deficiency (SIgAD), while partial IgA deficiency (PIgAD) was defined as IgA levels below lower limits of IgA normal range for age but higher than 7 mg/dL.Fifty-three patients (19 [35.8%] male and 34 [64.2%] female) with autoimmune polyendocrinopathy enrolled in the study. Parental consanguinity and positive family history of autoimmunity were reported in 38.0% and 52.9% of patients, respectively. Overall, IgA deficiency was observed in 5 (9.4%) patients including PIgAD in 3 (5.7%) and SIgAD in 2 (3.8%) patients. Among IgA deficient patients, the first autoimmune disorder was developed at earlier ages (The prevalence of IgA deficiency in patients with autoimmune polyendocrinopathy is higher than that in the general population. In these patients, immunologic workup may lead to early diagnosis of inborn error of immunity, which can positively impact the evolution of complications and even management of the autoimmune disorders.

Purpose This study aimed to assess the effect of COVID-19 on patients with IEIs, the potentially at-risk population, regarding the clinical course, complications, severity, and outcomes. Methods This two-phase study was conducted on patients from three referral immunodeficiency centers in Iran. At phase one, 98 IEI patients with COVID-19 infection were evaluated by telephone follow-up (TFU). At phase two, the demographic, clinical, and laboratory records of clinically confirmed 33 IEI patients with COVID-19 infection were collected and analyzed. Results At phase one, 16.3% represented COVID-19 infection without any report of pediatric intensive care unit (PICU) admission or death. During the second phase, combined immunodeficiency (CID) (42.4%) and predominantly antibody deficiencies (PADs) (33.3%) were the predominant immune defects. Atopy (27.3%) and lung disorders (27.3%) were the frequent pre-existing comorbidities. Organomegaly (p=0.030) and renal disorders (p=0.033) were significantly associated with the development of respiratory insufficiency. Cyanosis, tachypnea, intercostal retraction, and seizure were the chief complaints of patients who were more likely to progress respiratory insufficiency (p, being admitted to the PICU (p, and/or deceased (p. Laboratory evaluation revealed a marked positive correlation between D-Dimer (p=0.045), prothrombin time (p=0.045), C-reactive protein (p=0.041), proteinuria (p=0.013), ferritin (p=0.020), metabolic acidosis (p=0.003), and troponin (p=0.049) level with mortality. We detected a significant association between the chest X-ray pattern of COVID-19 infection with PICU admission (p=0.023) and death (p=0.046). Conclusion In the current study, patients with CID and PAD were introduced as patients at high risk of COVID-19 infection, who may need extra protective and therapeutic measurements.

BackgroundMendelian susceptibility to mycobacterial disease (MSMD) is an inborn error of immunity, resulting in susceptibility to weakly virulent mycobacteria and other intramacrophagic pathogens. Rheumatologic manifestations and vasculitis are considered rare manifestations in MSMD patients.Case presentationIn this study, we reported a 20-year-old female who was presented with recurrent lymphadenitis following bacillus Calmette-Guérin (BCG) vaccination and a history of recurrent disseminated rash diagnosed as leukocytoclastic vasculitis (LCV). A slight reduction in lymphocyte subsets including CD4+, CD19+, and CD 16 + 56 T-cell count, as well as an elevation in immunoglobulins level (IgG, IgA, IgM, IgE), were observed in the patient. Whole exome sequencing revealed a homozygous Indel-frameshift mutation, c.527_528delCT (p. S176Cfs*12), at the exon 5 of theIL12Bgene. She experienced symptom resolution after treatment with anti-mycobacterial agents and subcutaneous IFN-γ. We conducted a manual literature search for MSMD patients reported with vasculitis in PubMed, Web of Science, and Scopus databases. A total of 18 MSMD patients were found to be affected by a variety of vasculitis phenotypes mainly including LCV and Henoch-Schönlein purpura (HSP) with often skin involvement. Patients were all involved with vasculitis at the median age of 6.8 (2.6–7.7) years, nearly 6.1 years after the initial presentations. Sixteen patients (88.9%) hadIL12RB1defects and concurrentSalmonellainfection was reported in 15 (88.2%) patients.ConclusionThe lack of IL-12 and IL-23 signaling/activity/function and salmonella infection may be triggering factors for the development of leukocytoclastic vasculitis. IL12B or IL12RB1 deficiency and salmonellosis should be considered in MSMD patients with vasculitis.

BackgroundIgG4-related disease (IgG4RD) may initially present with pulmonary pseudotumor, making the diagnosis challenging particularly in patients prone to granulomatous inflammation. Here, we describe the first case of chronic granulomatous disease (CGD) with associated IgG4RD.Case presentationAn 8.5-year-old male was hospitalized two years ago with exertional dyspnea, mild cough, chest pain, and nocturnal sweating and was found to have a tumor-like mass in the right lung. The histopathologic findings were consistent with non-necrotizing granulomatous inflammation, central neutrophilic micro-abscess, and extensive peripheral fibrosis without any evidence for acid-fast bacilli or fungal elements. Treatment with prednisolone resulted in considerable symptom resolution. After 15 months, following the discontinuation of prednisolone by the patient, symptoms recurred, gradually exacerbated, and he developed anorexia and weight loss. The next chest spiral computed tomography (CT) scan showed a larger mass in the right lung, right lung collapse, and mediastinal metastasis. The abdominal ultrasound and CT scan were normal. In laboratory evaluation, low counts of B and T cells, normal natural killer (NK) cells, high levels of IgG4, and high inflammatory markers were detected. The nitro blue tetrazolium (NBT) test was zero in two consecutive evaluations. In virtue of high IgG4 level, the immunostaining of lung specimen was performed which was inconclusive for IgG4+cells, and staining for CD138 was not available. He was diagnosed with concurrent CGD and IgG4RD, but progressed to respiratory failure and died despite the reinstitution of steroid therapy.ConclusionsThe overlap between inborn errors of immunity (IEIs) and IgG4RD is not common. Further studies to investigate IgG subsets among IEI patients can help elucidate clinicopathological correlations between these two immune-mediated disorders.

Purpose: Combined immunodeficiency (CID) is characterized by profound defects in the development and function of both B and T cells. We aimed to investigate clinical and immunological phenotype in CID patients with and without pulmonary complications.Methods: This retrospective study was performed on patients with established diagnosis of CID registered between 2009 and 2020. Patients were divided into two groups based on the development of pulmonary complications, and their demographic, clinical, and laboratory characteristics were compared. All data were analyzed by SPSS software, and a P-value Results: 146 patients [56.8% male and 43.2% females] were enrolled in the study and divided into two groups of patients with (n=88) and without (n=58) pulmonary complications. In patients with pulmonary complications, oral candidiasis, failure to thrive, and otitis media, while in the other group, anemia, autoimmunity, rheumatologic disorders, and skin lesions had higher frequency, although not significant. Thoracic high resolution computed tomographies (HRCTs), available in 54.5% of patients with pulmonary complications, were compatible with pneumonia (39.8%), bronchiectasis (12.5%), pulmonary nodules (3.4%), atelectasis (1.1%), interstitial lung disease (1.1%), and pneumothorax (1.1%). Patients with pulmonary complications had lower number of T CD4+ but higher levels of CD8+ cells compared to patients without pulmonary complications (p=0.012 and p=0.005, respectively). The mortality rate was higher in patients with pulmonary complications compared to the other group (11.4% vs. 6.9%, p=0.597).Conclusion: Respiratory disorders in CID are common and require early periodic monitoring by respiratory tests and HRCT to avoid irreversible injuries.

Background: Post-vaccination BCG disease typically attests to underlying inborn errors of immunity (IEIs), with the highest rates of complications in patients with Mendelian susceptibility to mycobacterial disease (MSMD). However, therapeutic protocols for the management of BCG-osis (disseminated) and persistent BCG-itis (localized) are still controversial. Methods: Twenty-four Iranian patients with MSMD (BCG-osis or BCG-itis), followed from 2009 to 2020 in Tehran, were included in the study. Their medical records were retrospectively reviewed for demographics, clinical features, laboratory findings, and molecular diagnosis. The therapeutic protocol sheets were prepared to contain the types and duration of anti-mycobacterial agents. Results: BCG disease either as BCG-itis (33.3%) or BCG-osis (66.7%) was confirmed in all patients by positive gastric washing test (54.2%), microbial smear and culture (58.3%), or purified protein derivative (PPD) test (4.2%). The duration between BCG-osis onset and MSMD diagnosis was 21.6 months. All except three patients were initiated on second-line anti-mycobacterial agents with either a fluoroquinolone (levofloxacin: 15 mg/kg/day, ciprofloxacin: 20 mg/kg/day, ofloxacin: 15 mg/kg/day), aminoglycoside (amikacin: 10-15 mg/kg/day, streptomycin: 15 mg/kg/day), and/or macrolide (clarithromycin: 15 mg/kg/day) along with oral rifampin (10 mg/kg/day), isoniazid (15 mg/kg/day), and ethambutol (20 mg/kg/day). Three patients showed a clinical response to rifampin, despite in vitro resistance. Fourteen (58.3%) patients received also adjuvant subcutaneous IFN-γ therapy, 50 µ/m2 every other day. At the end of survey, most patients (n=22, 91.7%) were alive and two patients died following BCG-osis and respiratory failure. Conclusions: We recommend the early instigation of second-line anti-mycobacterial agents in MSMD patients with BCG disease.

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.

Febrile seizures are the most common form of childhood seizures. Although the literature associates certain micronutrients with febrile seizures, there is limited information about the effects of such micronutrients. This study aimed to determine the relationship between serum selenium level and simple febrile seizures in children. This case-control study was conducted in the Children's Hospital in Qazvin, Iran, in 2008. The serum selenium level of 30 children who experienced simple febrile seizures (case group) was measured and compared with that of 30 febrile children without seizure (control group). The serum selenium level was measured by flame atomic absorption spectrophotometer. Data were analyzed by using t-test. Mean ± standard deviation of serum selenium level in the case and control groups was 44.4 ± 10.9 and 63 ± 9.78 μg/dL, a significant difference (P0.001). In the case group, 18/30 patients (60%) had a serum selenium level below the norm of 46 μg/dL, whereas serum selenium level in the entire control group was within the normal range (P0.01). The serum selenium level in the children who had simple febrile seizures was significantly lower than in the nonseizure control group. It seems that there is an association between serum selenium deficiency and simple febrile seizures; however, further study is recommended.

Objective. Febrile seizures are the most common type of convulsion in children. The identification of influencing factors on incidence of the first febrile seizures is of prime priority. The aim of this study was to identify the risk factors of the first febrile seizures in Iranian children.Methods. In this case-control study 80 children aged 9 month to 5 years with their first febrile seizures were compared with 80 children with fever without seizure based on different risk factors in 2007.Results. There was significant difference between two groups regarding the gender, family history of febrile seizures, breast-feeding duration, and the body temperature (P<.05).Conclusion. Our study showed that factors including the gender, family history of febrile seizures, breast-feeding duration, and the body temperature are among the risk factors in occurrence of the first febrile seizure. Preventive measures to remove such risk factors could lead to lower the incidence of febrile seizures.