Are the most common food allergens in an Iranian atopic population compatible with worldwide reports? A systemic review and meta-analysis with molecular classification of frequent allergens.

BACKGROUND: Undesirable immunological responses to alimentary allergens are one of the hallmarks of atopic diseases. The prevalence of common food allergens is dissimilar among different communities with distinct nutritional habits and genetic characteristics. AIM: To assess the prevalence of the most common food allergens in Iran, using different reliable studies. METHODS: All studies determining sensitization to common food allergens that were indexed in PubMed, Web of Science, Google Scholar, ProQuest, Scopus, Iran Medex, and Magiran were included in this review. To perform a meta-analysis, STATA 14 and metaprop command was applied. A logistic-normal random-effects model with Freeman-Tukey double arcsin transformation was applied to combine the findings of different studies and evaluate their heterogeneity. Random pooled estimate (ES) (pooled prevalence), 95% confidence interval (95% CI) and p-value were determined. RESULTS: A total of 23 studies with data from a total of 6126 children and adults met the inclusion criteria for entering this meta-analysis. The respective pooled prevalence of a positive family history of allergy and positive specific IgE to at least one food allergen was 72% (95% CI: 66-77%) and 41% (95% CI: 33-49%), respectively. Our results in the total population revealed that allergic sensitization to egg yolk, cow's milk (CM), egg white, and wheat were 25% (95% CI: 16%-35%), 24% (95% CI: 19-29%), 23% (95% CI: 18%-28%), and 9% (95% CI: 6%-14%), respectively. Walnut, peanut, and soybean sensitization was detected in 23% (95% CI: 17%-31%), 23% (95% CI: 13%-33%), and 20% (95% CI: 12%-28%) of patients, respectively. Random pooled ES for sensitization to shrimp and fish was 32% (95% CI: 21-45%) and 12% (95% CI: 6-20%), respectively. The result of analysis in different age groups revealed that allergic sensitization to milk, egg white, and egg yolk declines in higher age groups; while shrimp sensitization increases in older patients. In patients with atopic dermatitis, egg white was the most frequent food allergen 29% (95% CI = 18-42%); while wheat was the least frequent 8% (95% CI = 4-14%). CONCLUSIONS: Considering the prevalence of different food allergens, the results of the current meta-analysis revealed that egg yolk and cow's milk had the second and third rate after shrimp, respectively. The high prevalence of sensitization to shrimp may be attributed to its high consumption in coastal areas and/or cross-reactivity of shrimp with some aeroallergens such as mites.

Three novel mutations in CYBA among 22 Iranians with Chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by defect in one of the components of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase enzyme. The enzyme is at least composed of membrane-bound subunits gp91-phox and p22-phox (also named cytochrome b558 ), and cytosolic ones p40-phox, p47-phox and p67-phox. A defect in the enzyme activity leads to impaired intracellular killing of phagocytic cells. The CYBA gene encoding p22-phox is located on chromosome 16q24. In this study, new genetic changes of CYBA gene in 22 Iranian patients with autosomal recessive-CGD (AR-CGD) were identified. Twenty-two patients with CGD were referred to Immunology, Asthma and Allergy Research Institute (IAARI) and enrolled in this study based on defect in NADPH oxidase activity, demographic data and clinical histories. All patients had p22-phox deficiency based on Western blotting. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs), and PCR followed by direct sequencing was performed to find p22-phox mutations. Mutation analysis of CYBA revealed 12 different mutations, including three novel mutations: one was deletion of exon 1, and two were point mutations in exon 3 (c.136G>A (p.Gly46Ser)), and exon 6 (c.388C>T (p.Gln130X)). Three new mutations of CYBA gene in four of 22 Iranian patients with AR-CGD were found. These three novel mutations can partly complete the database of Human Gene Mutation Database (HGMD) and other related ones. It can also be helpful for further prenatal diagnosis in the affected families. Given that currently bone marrow transplantation is considered to be the curative treatment for patients with CGD, finding mutations will also be useful for timely decision-making in bone marrow transplantation.

Clinical, Laboratory, and Molecular Findings for 63 Patients With Severe Combined Immunodeficiency: A Decade´s Experience.

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.

Long-term outcomes of fludarabine, melphalan and antithymocyte globulin as reduced-intensity conditioning regimen for allogeneic hematopoietic stem cell transplantation in children with primary immunodeficiency disorders: a prospective single center study.

Reduced-intensity conditioning (RIC) has offered many primary immunodeficiency disorder (PID) patients who are ineligible for myeloablative regimens a chance of cure. However, the beneficial role of RIC was questioned following reports suggesting higher chance of rejection and lower symptom resolution rate in mixed chimerism settings. Forty-five children affected by PIDs with a median age of 21 months underwent allogeneic hematopoietic stem cell transplantation in our institute from 2007 to 2013. All patients received an identical RIC regimen. Forty-one patients had successful primary engraftment (91%). Of the successful engraftments, 80% (n=33) had stable full donor chimerism at last contact. Overall, eleven transplant-related mortalities were reported including five patients due to sepsis, three children due to grade IV acute GvHD, two due to chronic GvHD and one patient due to sepsis after primary graft failure. The median post-transplantation follow-up of deceased patients was 55 days. Five-year overall survival and disease-free survival was 75.6% and 68.89%, respectively. All surviving patients with successful engraftment became disease free, regardless of having full or mixed chimerism. Our study suggests that RIC regimen provides satisfactory rates of successful engraftment and full chimerism. Furthermore, patients with mixed chimerism were stable in long-term follow-up and this chimerism status offered the potential to resolve symptoms of immunodeficiency.

Allergy to human insulin and specific immunotherapy with glargine; case report with review of literature.

Insulin has an important role in the treatment of diabetic patients. Further, it can result in undesirable side effects. One of the problems that are associated with insulin therapy is allergic reactions. Although insulin allergy is uncommon, especially in patients with type-2 diabetes, but when it occurs, its management can be difficult. We report a 55-year-old woman with poorly controlled type-2 diabetes and insulin allergy. She revealed hypersensitivity reactions including urticaria and respiratory symptoms, immediately after injection. So, specific immunotherapy with other insulin preparations was done. Finally, after specific immunotherapy, we were able to treat the patient with short- and long-acting analogs successfully.

Reduced-intensity conditioning hematopoietic SCT for pediatric patients with LAD-1: clinical efficacy and importance of chimerism.

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.