Reza Amin

Frequency and Clinical Manifestations of Patients with Primary Immunodeficiency Disorders in Iran: Update from the Iranian Primary Immunodeficiency Registry

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 (<5%). There is an increasing trend in recognition of more PID in the recent years. Construction of such registry is not only important for its epidemiological aspect but also for its role in increasing the physicians knowledge about such disorders.

PRIMARY IMMUNODEFICIENCY IN IRAN: FIRST REPORT OF THE NATIONAL REGISTRY OF PID IN CHILDREN AND ADULTS

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.

Consanguinity in primary immunodeficiency disorders; the report from Iranian Primary Immunodeficiency Registry.

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.

The relationship between serum 25 hydroxy vitamin D levels and asthma in children.

Purpose Asthma and other allergic disorders have increased over the past decades in nearly all nations. Many studies have suggested the role of vitamin D deficiency in both T-helper1 and T-helper2 diseases; however, the association between vitamin D, allergy, and asthma remains uncertain. In this study, the associations of 25-hydroxy vitamin D3 levels with asthma and with the severity of asthma were evaluated. Methods This cross-sectional study was conducted on 50 asthmatic children and 50 healthy controls aged 6-18 years. Serum 25-hydroxy vitamin D3 levels were determined and compared between the two groups. The relationship between serum vitamin D levels and pulmonary function test outcomes and eosinophil counts were examined in asthmatic patients. Results Univariate analysis of the relationship between asthma and vitamin D showed that decreased vitamin D levels were associated with significantly increased odds of asthmatic state (P=0.002). In a multivariate analysis after adjustment for age, body mass index, and sex, the relationship between vitamin D and asthma increased. In asthmatic patients, 25-hydroxy vitamin D levels had direct and significant correlations with both predicted FEV1 (R2=0.318; P=0.024) and FEV1/FVC (R2=0.315; P=0.026). There were no associations between vitamin D level and eosinophil counts, duration of disease, and the number of hospitalization or unscheduled visits in the previous year (P>0.05). Conclusions These results showed that serum 25-hydroxy vitamin D levels were inversely associated with asthma, and there was a direct and significant relationship between vitamin D levels and pulmonary function test outcomes in asthmatic children. An interventional study in asthmatic patients with low serum vitamin D concentration may establish a causal relationship between asthma and vitamin D.

Prevalence of allergic rhinitis and nasal smear eosinophilia in 11‐ to 15 yr‐old children in Shiraz

Allergic rhinitis (AR) is a common condition among schoolchildren. The prevalence rate of AR differs among countries and even among regions within the same country. The objective of this study was to determine the prevalence of nasal symptoms and signs of AR and nasal smear eosinophilia in 11‐ to 15‐yr‐old children in Shiraz. A total of 4584 children aged 11–15 yr of both sexes were surveyed from May 1995 to April 1996, and nasal symptoms and signs of AR (sneezing, rhinorrhea, nasal blockage, itching, color change, mucosal swelling, nasal wetness, and nasal crease), based on questionnaire and ear, nose and throat (ENT) examination were recorded. In addition, smears were taken from nasal secretions and stained. The results compared with nasal smears related to 340 healthy children. 1008 (22%) schoolchildren had nasal symptoms of AR (based on the questionnaire), 445 (9.7%) were identified as having nasal symptoms and signs of AR (based on the questionnaire and ENT specialist examination), and 226 (5.8%) had nasal symptoms and signs of AR associated with nasal eosinophilia (based on the questionnaire, ENT specialist examination and positive nasal smear for eosinophilia). Nasal eosinophilia was present in 274 (62%) children with nasal symptoms and signs of AR. This survey showed that prevalence of nasal symptoms and signs of AR was high in schoolchildren in Shiraz. Nasal smear eosinophilia had a diagnostic specificity of 96% and sensitivity of 62% and seems to be a potentially valuable test for AR.

Long-term evaluation of a historical cohort of Iranian common variable immunodeficiency patients

Objectives: Common variable immune deficiency (CVID) is the most frequent form of symptomatic primary immunodeficiency disease, characterized by hypogammaglobulinemia, recurrent infections and increased predisposition to autoimmunity and malignancies. The aim of this study was to reconsider important points of previously performed studies on Iranian CVID patients diagnosed and followed from 1984 to 2013. Methods: Diagnosis was made using approved criteria including reductions of serum levels of immunoglobulins and exclusion of well-known single gene defects in individuals with an age >4 years and evidence of specific antibody deficiency. Results: Detailed information on demographic data, survival rates, clinical phenotypes, immunologic and genetic data and treatment of 173 patients are provided. The early onset presentation (74.5%) and rate of consanguineous marriage (61.2%) were considerably higher in our cohort. Our study revealed clinically related correlations regarding consanguinity, the population of naïve CD4+ T cells and switched-memory B cells, cytokine levels and special genetic factors (including HLA and AID genes). Conclusion: Despite current efforts, more comprehensive studies are needed, especially for classification and investigation of the genetic background and prognostic factors for patients with CVID in order to better managment and followup of patinets.

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

Background: Combined immunodeficiencies (CIDs) are diseases of defective adaptive immunity with diverse clinical phenotypes. Although CIDs are more prevalent in the Middle East than Western countries, the resources for genetic diagnosis are limited. Objectives: This study aims to characterize the categories of patients with CIDs in Iran clinically and genetically. Methods: Clinical and laboratory data were obtained from 696 patients with CIDs. Patients were subdivided into those with syndromic (344 patients) and nonsyndromic (352 patients) CIDs. Targeted DNA sequencing was performed on 243 (34.9%) patients. Results: The overall diagnostic yield of the 243 sequenced patients was 77.8% (189 patients). The clinical diagnosis of hyper‐IgE syndrome (P < .001), onset of disease at greater than 5 years (P = .02), and absence of multiple affected family members (P = .04) were significantly more frequent in the patients without a genetic diagnosis. An autosomal recessive disease was found in 62.9% of patients, reflecting the high rate of consanguinity in this cohort. Mutations impairing VDJ recombination and DNA repair were the most common underlying causes of CIDs. However, in patients with syndromic CIDs, autosomal recessive mutations in ataxia‐telangiectasia mutated (ATM), autosomal dominant mutations in signal transducer and activator of transcription 3 (STAT3), and microdeletions in 22q11.21 were the most commonly affected genomic loci. Patients with syndromic CIDs had a significantly lower 5‐year survival rate rather than those with nonsyndromic CIDs. Conclusions: This study provides proof of principle for the application of targeted next‐generation sequencing panels in countries with limited diagnostic resources. The effect of genetic diagnosis on clinical care requires continued improvements in therapeutic resources for these patients.

Initial Intravenous γ-Globulin Treatment Failure in Iranian Children with Kawasaki Disease

The purpose of this study was to determine the initial rates of intravenous ?‐globulin treatment (IVIG) failure in Kawasaki disease (KD) and their predisposing factors. This study was a retrospective analysis of the initial response to IVIG (2 g/kg), assessed from the medical reports of all patients admitted to Namazee Hospital pediatric ward, from March 1998 to March 2002, and who fulfilled the criteria for KD. Data were available for 64 patients, 58 of whom (90.6%) became afebrile 48 hours after completion of the initial dose of IVIG (Group I) and six (9.4%) who remained febrile (Group II). Two patients had a prompt response to a second dose of IVIG. In Group I, five patients (8.6%) developed coronary artery disease, seen on echocardiography. In Group II, two patients (33.3%) developed coronary artery disease. No significant difference was found in the prevalence of coronary artery disease between the two groups (p = 0.12), or in age or gender. The rate of initial treatment failure was 9.4% in this cohort of patients, which is comparable with previous reports. No predictive factors such as coronary artery disease, age or gender were found for initial treatment failure in KD.

Pulmonary Function Test in Transfusion-Dependent β-Thalassemia Major Patients: A Pilot Study

Lung involvement is one of known complications of thalassemia. The aim of this study was to determine predominant type of pulmonary dysfunction and its relationship to iron overload in β-thalassemia children. Fifty thalassemia major children with treatment of regular blood transfusion and desferrioxamine participated in the study. Thirty-three boys and 17 girls (median age 12.5 years) with β-thalassemia enrolled in the study. Other information including body mass index, hematocrit, and the number of years of blood transfusion were recorded. Serum ferritin level and hematocrit were 3346 ± 1667 mg/dL and 27.7 ± 2, respectively. Pulmonary function tests were performed in all subjects for detecting pulmonary dysfunction. Thirty-five patients (70%) with thalassemia had abnormal result of spirometry. Obstructive airway disease based on reduced forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC) ratio <80% was detected in 4 patients (8%). Six patients (12%) showed restrictive pattern, as defined by a reduction FVC <80% and FEV1/FVC ratio ≥80%. In this study, small airway involvement based on presence of forced expiratory flow (FEF25%–75%) <60%, FEV1/FVC ratio >70%, and FVC >80% was detected in 25 subjects (50%). Decreased values of peak expiratory flow rate (PEF) were detected in 23 (46%) and low FEV1 in 10 (20%) subjects. There was no significant correlation between abnormal pulmonary function test and serum ferritin level in children with thalassemia. This study showed small airway disease was predominant abnormality in thalassemia patients, although additional larger studies are needed to evaluate underlying mechanisms and validate these findings.

Exercise-Induced Asthma in Asthmatic Children of Southern Iran

Background: Asthma is a common illness, especially among children. Exercise-induced asthma is an important consideration, both as a factor, limiting physical activity of patients, and also as an indicator of poor long term control. We investigated pre-Valence of exercise-induced asthma in a group of asthmatic children living in southern Iran. Methods: We conducted treadmill exercise challenge test in 40 young asthmatic patients aged 6 to 18. After 8 minutes exercise to achieve 80% of maximum heart rate predicted for age, patients were examined and spirometry values recorded at frequent intervals. We defined exercise-induced asthma as 10% or more decline in Forced Expiratory Volume in one second (FEV1) within 30 minutes after exercise challenge. Results: Of 40 patients evaluated, 22 patients (55% of total) met our criteria for exercise-induced asthma. Most positive responses (7 of 22, 31.8%) occurred at about 10 minutes after exercise. Cough was the most consistent sign (18 of 22 patients, 81%). In 2 patients (9%), FEV 1 decline did not accompany any symptom or sign. Conclusion: We concluded that Exercise- induced asthma occurs in a relatively smaller subset of southern Iranian asthmatic children. Also treadmill exercise challenge performed by a trained staff, following standard protocol and using enough monitoring and precautions is safe and diagnostic in children and adolescents.