Publications by authors named "Behzad Darabi"

12 Publications

  • Page 1 of 1

Autoimmune Manifestations among Patients with Monogenic Inborn Errors of Immunity.

Pediatr Allergy Immunol 2021 Mar 27. Epub 2021 Mar 27.

Department of Pediatrics, Hamedan University of Medical Sciences, Hamedan, Iran.

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.
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http://dx.doi.org/10.1111/pai.13510DOI Listing
March 2021

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity.

Int Arch Allergy Immunol 2020 2;181(9):706-714. Epub 2020 Jul 2.

Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

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.
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http://dx.doi.org/10.1159/000508817DOI Listing
February 2021

The association between caesarean section and childhood asthma: an updated systematic review and meta-analysis.

Allergy Asthma Clin Immunol 2019 29;15:62. Epub 2019 Oct 29.

5School of Medicine, Ilam University of Medical Sciences, Ilam, Iran.

Background: Investigating the association between caesarean section (SC) and childhood asthma has shown contradictory results in different studies. The present study was conducted to determine the association between SC and childhood asthma.

Material And Method: The present study was conducted based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. All the steps of the study were conducted independently by two reviewers from the inception until February 1, 2019. In case of disagreement, the third reviewer resolved it. We searched international online databases, including Scopus, Cochrane Library, PubMed/Medline, Embase, Web of Science (ISI), Science Direct, and Google scholar. The results of studies were combined using random effects model, and heterogeneity was measured through I index and Cochran's Q test. Comprehensive Meta-Analysis Software was used for meta-analysis. The significance level of all tests was considered to be P < 0.05.

Results: The heterogeneity rate was high (I = 67.31%, P < 0.001) in 37 studies. The results showed that SC increased the risk of childhood asthma (RR (relative risk) = 1.20 [95% CI 1.15-1.25, P < 0.001]). The association between emergency and elective SC and childhood asthma was significant with RR of 1.18 (95% CI 1.07-1.29, P < 0.001) in 13 studies and 1.23 (95% CI 1.20-1.26, P < 0.001) in 13 studies, respectively. The subgroup analysis for RR of childhood asthma in SC indicated that study design (P = 0.306), prospective/retrospective studies (P = 0.470), quality of studies (P = 0.514), continent (P = 0.757), age of diagnosis (P = 0.283) and year of publication (P = 0.185) were not effective in the heterogeneity of studies. Sensitivity analysis by removing one study at a time indicated that the overall estimate is robust.

Conclusion: According to the meta-analysis, SC (overall, elective, and emergency) increased the risk of childhood asthma. Therefore, it is hoped that developing clinical guidelines and implementing appropriate management plans would diminish the risk of asthma.
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http://dx.doi.org/10.1186/s13223-019-0367-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820931PMC
October 2019

Fourth Update on the Iranian National Registry of Primary Immunodeficiencies: Integration of Molecular Diagnosis.

J Clin Immunol 2018 10 9;38(7):816-832. Epub 2018 Oct 9.

Pediatric Infections Research Center, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: 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.

Method: 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1007/s10875-018-0556-1DOI Listing
October 2018

Comparison of Common Monogenic Defects in a Large Predominantly Antibody Deficiency Cohort.

J Allergy Clin Immunol Pract 2019 03 19;7(3):864-878.e9. Epub 2018 Sep 19.

Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.

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 μ 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 μ 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 μ 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.
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http://dx.doi.org/10.1016/j.jaip.2018.09.004DOI Listing
March 2019

Effect of childhood BMI on asthma: a systematic review and meta-analysis of case-control studies.

BMC Pediatr 2018 04 26;18(1):143. Epub 2018 Apr 26.

Department of Pediatrics, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran.

Background: Asthma is a multifactorial syndrome that threatens the health of children. Body mass index (BMI) might be one of the potential factors but the evidence is controversial. The aim of this study is to perform a comprehensive meta-analysis to investigate the association between asthma and BMI.

Methods: Electronic databases including, Web of Science, Pubmed, Scopus, Science Direct, ProQuest, up to April 2017, were searched by two researchers independently. The keywords "asthma, body mass index, obesity, overweight, childhood and adolescence" were used. Random and fixed effects models were applied to obtain the overall odds ratios (ORs) and standardized mean difference (SMD). Heterogeneity between the studies was examined using I and Cochrane Q statistics.

Results: After reviewing 2511 articles, 16 studies were eligible for meta-analysis according to inclusion/exclusion criteria. A meta-analysis from 11 case-control studies revealed OR of asthma and overweight as OR = 1.64; (95% Confidence Interval (CI): 1.13-2.38) and from 14 case-control studies, OR for asthma and obesity was OR = 1.92 (95% CI: 1.39-2.65), which indicated that risk of asthma in overweight and obese children and adolescence was significantly higher (1.64 and 1.92 times) than that of individuals with (p-value < 0.01 for underweight/normal weight in both cases). Furthermore, there was a significant relationship between asthma and BMI > 85 percentile according to SMD SMD = 0.21; (95%CI: 0.03-0.38; p-value = 0.021).

Conclusions: The results showed a significant relationship between BMI (obesity/overweight) and asthma among children and adolescents. It is important to study the confounding factors that affect the relationship between asthma and BMI in future epidemiological researches.
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http://dx.doi.org/10.1186/s12887-018-1093-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922016PMC
April 2018

Determination of the Most Common Indoor and Outdoor Allergens in 602 Patients with Allergic Symptoms Using Specific IgE Local Panel.

Iran J Allergy Asthma Immunol 2017 Aug;16(4):298-306

Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran AND Department of Immunology, Children Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Aeroallergens play an important role in developing allergic diseases. The aim of this study was to determine the outdoor and indoor sensitization using a specific regional panel of aeroallergens in allergic patients. All patients with allergic symptoms referred to Immunology, Asthma and Allergy Research Institute (IAARI) in Tehran, Iran from December 2010 to July 2013 entered this cross sectional study. We evaluated serum samples for specific IgE against 20 selected aeroallergens provided by a specific panel (RIDA Allergy Screen test, IAARI panel). A p value less than 0.05 was considered as significant. The patients (n=602) were 49.8 % male and 50.2% female. The median age was 9 years. Positive specific IgE at least to one allergen was 53.2%. The percentages of patients with only outdoor or indoor sensitization were 37.5 and 19.7%, respectively. Moreover, 42.8% showed sensitization to both indoor and outdoor aeroallergens. The most common outdoor aeroallergens in decreasing order were plane tree (32.8%), Bermuda grass (32.2%), timothy grass (30.6%), saltwort (28.4%). The percentage of specific IgE to indoor allergens including mold and mite were 23.8 % and 22.2%, respectively. There was a statistically significant relationship between specific IgE to timothy grass and mold allergens between two genders (p=0.04 and p=0.02, respectively).The results of this study shows that outdoor aeroallergens can be considered as the most common causes of allergic symptoms in our allergic patients.
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August 2017

Impact of IgE-mediated Food Allergy on Parental Quality of Life in Iranian Patients.

Iran J Allergy Asthma Immunol 2016 Oct;15(5):372-380

Department of Allergy and Clinical Immunology, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Food allergy is a common disorder especially in the first years of life. Strict avoidance of the responsible food is the most effective therapeutic measure so far. But this continuous vigilance could be stressful for the patient and family and decreases their quality of life (QOL). This survey was designed to evaluate the impact of IgE-mediated food allergy on parental QOL in Iranian patients and to develop a valid Persian version of "Food Allergy Quality Of Life- Parental Burden (FAQL-PB) questionnaire". 90 patients (28 females, 62 males) and their parents who were referred to the clinic of Allergy in Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran were enrolled. The questionnaire was translated with scientific method and its reliability was approved in a pilot study (ICC=0.75, cronbach-α=0.90). Among all patients the most common allergens were wheat (60%) and cow's milk (42%). The patient's age (p=0.02), parent's gender (p=0.004), mother's age (p=0.02), duration of the disease (p=0.048), and allergen multiplicity (p=0.004) were found to have the most significant correlation with family and social activity (FSA) domain. The most meaningful associations were achieved between parent's gender (p<0.001) and emotional issues (EM); as well as meal preparation (MP) with patient's age (p=0.02), parent's gender (p<0.0001) and also allergen multiplicity (p= 0.003); likewise nutrition and health concern (NH) domain with parent's gender (p<0.001). Anaphylaxis's history did not place any burden on each domain. It was concluded that presence of food allergic patients in families could considerably affect all domains of QOL.
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October 2016

Evaluation of antibody response to polysaccharide vaccine and switched memory B cells in pediatric patients with inflammatory bowel disease.

Gut Liver 2014 Jan 14;8(1):24-8. Epub 2013 Aug 14.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran. ; Molecular Immunology Research Center and Department of Immunology, Tehran University of Medical Sciences School of Medicine, Tehran, Iran.

Background/aims: Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract, whose etiologies are still unknown. This study was performed to evaluate the humoral immune response in terms of B cell functions in selected IBD patients.

Methods: Eighteen pediatric patients with IBD, including 12 cases of ulcerative colitis (UC) and six with Crohn disease (CD), were enrolled in this study. The pneumococcal vaccine was injected in all patients, and the IgG antibody level to the polysaccharide antigen was measured before and 4 weeks after injection. The B cell switch-recombination process was evaluated.

Results: Five patients with IBD (three CD and two UC) had defects in B cell switching, which was significantly higher than in controls (p=0.05). Ten patients had a specific antibody deficiency and exhibited a higher frequency of bacterial infection than the healthy group. The mean increased level of IgG after vaccination was lower in IBD patients (82.9±32.5 µg/mL vs 219.8±59.0 µg/mL; p=0.001). Among the patients who had an insufficient response, no significant difference in the number of switched memory B-cell was observed.

Conclusions: A defect in B lymphocyte switching was observed in pediatric IBD patients, and especially in those patients with CD. Owing to an increased risk of bacterial infections in those patients with antibody production defects, pneumococcal vaccination could be recommended. However, not all patients can benefit from the vaccination, and several may require other prophylactic methods.
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http://dx.doi.org/10.5009/gnl.2014.8.1.24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916683PMC
January 2014

TNF-alpha single nucleotide polymorphisms in atopic dermatitis.

Eur Cytokine Netw 2012 Oct-Dec;23(4):163-5

Pediatrics Center of Excellence, Children's Medical Center.

Tumor necrosis factor-alpha (TNF-α) could be considered as potential biomarkers in atopic dermatitis (AD), while its level could be influenced by cytokine single gene polymorphisms (SNP). This study was performed in 89 pediatric patients with AD and 137 controls to assess polymorphisms of the TNF-α gene at positions -308 and -238, using the polymerase chain reaction and the sequence-specific primers method. The highest positive allelic association that made the patients susceptible to AD was seen for TNF-α -238/G (p<0.001) and TNF-α -308/G (p = 0.003). The GG genotypes at TNF-α -238 and TNF-α -308, were both significantly higher in the patients with AD, compared to the controls (p<0.01). The GG haplotype at TNF-α (-308,-238) was seen in 92.7% of the patients, which was significantly higher than the controls (p<0.001), while a negative haplotypic association with AD was seen for TNF-α (-308, -238) AG and GA (p<0.01). This study showed that the AG genotype of TNF-α -308, associated with a high production of cytokines, was significantly decreased in patients with AD, while the low-producing GG genotype, which could lead to low production of TNF-α, was over-expressed in the atopic patients.
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http://dx.doi.org/10.1684/ecn.2012.0323DOI Listing
July 2013

Methodologic considerations in trials assessing prevention of asthma exacerbation by vitamin D supplementation.

J Allergy Clin Immunol 2011 Nov 23;128(5):1131; author reply 131-2. Epub 2011 Jul 23.

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http://dx.doi.org/10.1016/j.jaci.2011.06.032DOI Listing
November 2011

Health-related quality of life in primary antibody deficiency.

Iran J Allergy Asthma Immunol 2011 Mar;10(1):47-51

Research Center for Immunodeficiency, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Patients with primary antibody deficiencies (PAD) are susceptible to recurrent and chronic infections and a variety of complications. This study was performed to assess quality of life (QoL) of PAD patients who were under long term treatment and regular follow-up.Thirty six adults with proved diagnosis of PAD, who had received regular intravenous immunoglobulin replacement therapy, were enrolled in this study. The QoL of selected PAD patients was measured by Medical Outcomes Study 36-item Short-Form (SF-36) Health Survey questionnaire.The patients with PAD showed significantly reduced scores in physical component in comparison with healthy age-sex matched control subjects (60.2±20.1 vs. 85.5±4.7, P<0.001). Mental component score was also significantly decreased in the patient's group (59.8±19.5 vs. 72.3±3.4, P=0.002). There was a reverse association between SF-36 scores and number of infections episodes (r=-0.73 P=0.003). The patients with long delay diagnosis showed significantly lower SF-36 scores (r=-0.62, P=0.003).The patients with PAD who were diagnosed timely and managed appropriately seem to have lower complications and better QoL. However, the patients with severe phenotypes and long delay in diagnosis showed lower QoL, even in medical management.
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http://dx.doi.org/010.01/ijaai.4751DOI Listing
March 2011