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1.
Iran J Allergy Asthma Immunol ; 23(2): 158-167, 2024 Apr 07.
Article in English | MEDLINE | ID: mdl-38822511

ABSTRACT

Patients with inborn errors of immunity (IEI) are among the high-risk groups regarding COVID-19. Receiving booster doses (third and fourth) in addition to the standard doses is recommended in these patients. This study investigated the antibody response before and after a booster dose of Sinopharm vaccine in IEI patients.  Thirty patients (>12 years) with antibody deficiencies, referred to Imam Khomeini Hospital and Children's Medical Center in Tehran, were enrolled in this prospective cross-sectional study. All patients were fully vaccinated with the BBIBP-CorV vaccine (2 doses of Sinopharm). Initial measurements of anti-receptor-binding domain (anti-RBD) and anti-nucleocapsid (anti-N) IgG antibody responses were conducted by enzyme-linked immunosorbent assay (ELISA). Subsequently, all patients received a booster dose of the vaccine. Four to six weeks after booster injection, the levels of antibodies were re-evaluated.  Twenty patients with common variable immunodeficiency (CVID), 7 cases with agammaglobulinemia and 3 patients with hyper IgM syndrome were studied. Anti-RBD IgG and anti-N IgG antibodies increased in all patients after the booster. Our results indicated the need of receiving booster doses of the COVID-19 vaccine in patients with antibody deficiencies, even for enhancing humoral immune response specially in patients with CVID.


Subject(s)
Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Immunization, Secondary , Immunoglobulin G , SARS-CoV-2 , Humans , Male , COVID-19/immunology , COVID-19/prevention & control , Female , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , SARS-CoV-2/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Adult , Immunoglobulin G/blood , Immunoglobulin G/immunology , Cross-Sectional Studies , Adolescent , Iran , Prospective Studies , Antibody Formation/immunology , Vaccines, Inactivated/immunology , Vaccines, Inactivated/administration & dosage , Child , Middle Aged , Young Adult
2.
Pediatr Allergy Immunol ; 34(7): e13990, 2023 07.
Article in English | MEDLINE | ID: mdl-37492921

ABSTRACT

BACKGROUND: In order to support the comprehensive classification of Leukocyte Adhesion Deficiency-I (LAD-I) severity by simultaneous screening of CD11a/CD18, this study assessed clinical, laboratory, and genetic findings along with outcomes of 69 LAD-I patients during the last 15 years. METHODS: Sixty-nine patients (40 females and 29 males) with a clinical phenotype suspected of LAD-I were referred to Immunology, Asthma, and Allergy research institute, Tehran, Iran between 2007 and 2022 for further advanced immunological screening and genetic evaluations as well as treatment, were enrolled in this study. RESULTS: The diagnosis median age of the patients was 6 months. Delayed umbilical cord separation was found in 25 patients (36.2%). The median diagnostic delay time was 4 months (min-max: 0-82 months). Forty-six patients (66.7%) were categorized as severe (CD18 and/or CD11a: below 2%); while 23 children (33.3%) were in moderate category (CD18 and/or CD11a: 2%-30%). During the follow-ups, 55.1% of children were alive with a mortality rate of 44.9%. Skin ulcers (75.4%), omphalitis (65.2%), and gingivitis (37.7%) were the most frequent complaints. Genetic analysis of the patients revealed 14 previously reported and three novel pathogenic mutations in the ITGB2 gene. The overall survival of patients with and without hematopoietic stem cell transplantation was 79.3% and 55.6%, respectively. CONCLUSION: Physicians' awareness of LAD-I considering delayed separation of umbilical cord marked neutrophilic leukocytosis, and variability in CD11 and CD18 expression levels, and genetic analysis leads to early diagnosis and defining disease severity. Moreover, the prenatal diagnosis would benefit families with a history of LAD-I.


Subject(s)
CD18 Antigens , Leukocyte-Adhesion Deficiency Syndrome , Male , Pregnancy , Female , Humans , CD18 Antigens/genetics , Leukocyte-Adhesion Deficiency Syndrome/diagnosis , Leukocyte-Adhesion Deficiency Syndrome/genetics , Delayed Diagnosis , Iran , Leukocytes/metabolism
3.
Genes Immun ; 24(4): 207-214, 2023 08.
Article in English | MEDLINE | ID: mdl-37516813

ABSTRACT

Severe combined immunodeficiency (SCID) is one of the severe inborn errors of the immune system associated with life-threatening infections. Variations in SCID phenotypes, especially atypical SCID, may cause a significant delay in diagnosis. Therefore, SCID patients need to receive an early diagnosis. Here, we describe the clinical manifestations and genetic results of four SCID and atypical SCID patients. All patients (4 males and 4 females) in early infancy presented with SCID phenotypes within 6 months of birth. The mutations include RAG2 (p.I273T,p.G44X), IL7R (p.F361WfsTer17), ADA (c.780+1G>A), JAK3 (p.Q228Ter), LIG4 (p.G428R), and LAT (p.Y207fsTer33), as well as a previously reported missense mutation in RAG1 (p.A444V). The second report of LAT deficiency in SCID patients is presented in this study. Moreover, all variants were confirmed in patients and their parents as a heterozygous state by Sanger sequencing. The results of our study expand the clinical and molecular spectrum associated with SCID and leaky SCID phenotypes and provide valuable information for the clinical management of the patients.


Subject(s)
Severe Combined Immunodeficiency , Male , Female , Humans , Severe Combined Immunodeficiency/diagnosis , Severe Combined Immunodeficiency/genetics , Exome Sequencing , Mutation , Phenotype
4.
Iran J Allergy Asthma Immunol ; 22(1): 119-123, 2023 Feb 20.
Article in English | MEDLINE | ID: mdl-37002626

ABSTRACT

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder more common in autosomal recessive (AR) than X-linked in Iran. This study aimed to assess whether having a child with AR-CGD would increase the likelihood of the next child being affected by CGD. Ninety-one families with at least one child affected by AR-CGD entered this study. Out of the 270 children, 128 were affected by AR-CGD. We used a cross tab for the odds ratio (OR) calculation, in which exposure to a previously affected child and the next child's status were evaluated. This study illustrated that the chances of having another child afflicted with AR-CGD are significantly increased if the previous child had AR-CGD (OR=2.77, 95% CI=1.35-5.69).Althoug h AR disorders affect 25% of each pregnancy, we showed that the chance that the next child would be affected by CGD, given that the previous child was affected, is 2.77 times greater than in families with a normal child. It is recommended to warn families with one or more affected children to evaluate the risk of CGD in their subsequent pregnancies with prenatal diagnosis.


Subject(s)
Granulomatous Disease, Chronic , Humans , Child , Granulomatous Disease, Chronic/diagnosis , Granulomatous Disease, Chronic/epidemiology , Granulomatous Disease, Chronic/genetics , NADPH Oxidases/genetics , Genes, Recessive , Genes, X-Linked , Iran , Mutation
5.
Iran J Allergy Asthma Immunol ; 21(3): 232-240, 2022 Jun 18.
Article in English | MEDLINE | ID: mdl-35822674

ABSTRACT

Oral immunotherapy (OIT) is a novel approach to desensitization and tolerance induction in food allergy patients. This study aimed to design and implement a new wheat OIT protocol, evaluate its efficacy in tolerance induction, and assess specific immunoglobulin-E (IgE) and regulatory T cell changes. From 2015 to 2017, 26 patients with confirmed IgE-mediated hypersensitivity to wheat were treated via oral immunotherapy (OIT). Patients with prior anaphylactic episodes underwent OIT using the rush method. Specific IgE concentrations and the number of regulatory T cells (CD4+ CD25+ FOXP3+ T cells) were measured using Allergy Screen immunoblot assay and flow cytometry, respectively. This study was registered in the Iranian Registry of Clinical Trials (IRCT20181220042066N1). The results revealed success rates of 100% and 93.3% for desensitization and tolerance. Specific IgE was significantly reduced after 12 months of OIT. No significant change in regulatory T cell numbers was observed. In view of the promising findings of this study, the proposed OIT protocol could be viewed as an effective and valuable method to induce tolerance and desensitization in wheat allergic patients.


Subject(s)
Desensitization, Immunologic , Food Hypersensitivity , Administration, Oral , Allergens/therapeutic use , Desensitization, Immunologic/methods , Food Hypersensitivity/therapy , Humans , Immune Tolerance , Immunoglobulin E , Immunologic Factors , Iran , Triticum
6.
J Mycol Med ; 31(1): 101106, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33395593

ABSTRACT

Invasive Rasamsonia spp. infections are rare and usually associated with chronic granulomatous disease (CGD). We present a case of pulmonary and possible cerebral infection due to Rasamsonia argillacea in a girl with CGD receiving no primary antifungal prophylaxis. There was a fatal outcome despite the combination of antifungal therapy and surgical interventions. We also conducted a literature review on reported invasive Rasamsonia spp. infections in the setting of CGD.


Subject(s)
Eurotiales/pathogenicity , Granulomatous Disease, Chronic/complications , Invasive Fungal Infections/diagnosis , Invasive Fungal Infections/etiology , Lung Diseases, Fungal/diagnostic imaging , Lung Diseases, Fungal/etiology , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Eurotiales/drug effects , Fatal Outcome , Female , Humans , Infant , Invasive Fungal Infections/drug therapy , Lung Diseases, Fungal/drug therapy , Microbial Sensitivity Tests , Sequence Analysis, DNA , Tomography, X-Ray Computed
7.
Allergol. immunopatol ; 48(5): 424-429, sept.-oct. 2020. tab, graf
Article in English | IBECS | ID: ibc-201832

ABSTRACT

INTRODUCTION AND OBJECTIVES: Considering that no studies have been done on a comprehensive review of Serum sickness-like reactions patients (SSLRs) at a referral center in Iran so far, this study aimed to determine the clinical and laboratory characteristics of children with SSRL in Tehran Children's Medical Center. PATIENTS: The present study was a registry-based study in which the data of 94 SSLRs patients registered in a two-year period were investigated. Confirmation of fever, rash, urticaria, arthralgia / arthritis and history of antibiotic consumption up to three weeks before were the criteria for the diagnosis. RESULTS: Fifty-one (54 %) patients were male with mean age of 56 ± 30 months and there was no significant difference in the age of the two genders. The mean onset of symptoms before hospitalization were 3.8 ± 2.7 days (1-14 days); this mean was significantly higher in males than in females (4.6 ± 2.9 versus 2.9 ± 1.7 days, P-value = 0.003). Among antibiotics, Co-amoxiclav and Cefixime antibiotics had the most frequency by 31 % and 33 %, respectively as the most important incidence factor of SSLRs. The mean duration of consumption of culprit medications in the incidence of SSLRs was 5.6 ± 2.9 days with a range of 1-15 days. CONCLUSIONS: This study showed that among the antibiotics, Co-amoxiclav and Cefixime are more prevalent and a review of prescribing these two antibiotics for the treatment of the children's infections is essential if this finding is confirmed by other Iranian scholars


No disponible


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Anemia, Sickle Cell/drug therapy , Drug Hypersensitivity/epidemiology , Drug-Related Side Effects and Adverse Reactions/epidemiology , Anti-Bacterial Agents/adverse effects , Iran/epidemiology , Incidence
8.
Iran J Allergy Asthma Immunol ; 19(3): 305-309, 2020 Jun 23.
Article in English | MEDLINE | ID: mdl-32615664

ABSTRACT

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by genetic defects in the Bruton tyrosine kinase (Btk) gene. XLA is characterized as an antibody deficiency by recurrent bacterial infections, the absence of peripheral B cells, and profound reductions in all immunoglobulin isotypes. This study aims to report the clinical and genetic features of five Iranian patients with XLA. Five male cases with recurrent bacterial infection entered this study based on clinical evaluation and Immunological screening tests. The levels of T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) were also measured in dried blood spot (DBS) samples. Sanger sequencing was applied to PCR products of DNA samples of the patients for genetic studies. All patients were from unrelated families with a mean age of 6.7 years (2.5-11) at the time of diagnosis with 4.8 mean years of delay in diagnosis. The most frequent clinical manifestations were recurrent respiratory infections and arthritis. In these patients, five previously reported mutations were found including four mutations (p.Q496X, p.Q497X, p.R520X, and p.R641H) in the Kinase domain besides one mutation (p.L37P) in the pleckstrin homology (PH) domain. Evaluations of KREC and TREC level in patients' DBS showed low-to-undetectable copies of KREC (0-2 copies/3.2mm DBS) with normal copies of TREC. As patients with XLA have complete immunoglobulin defects and develop severe and recurrent infections, early diagnosis would be beneficial for the improvement of their quality of life. The study results may provide valuable information for the diagnosis, genetic counseling and prenatal diagnosis for the patients and their family members and emphasize performing KREC as an early diagnostic test in patients with XLA.


Subject(s)
Agammaglobulinemia/diagnosis , Genetic Diseases, X-Linked/diagnosis , Agammaglobulinaemia Tyrosine Kinase/genetics , Agammaglobulinemia/drug therapy , Agammaglobulinemia/genetics , Agammaglobulinemia/immunology , B-Lymphocytes/immunology , Bacterial Infections/genetics , Child , Child, Preschool , Early Diagnosis , Genetic Diseases, X-Linked/drug therapy , Genetic Diseases, X-Linked/genetics , Genetic Diseases, X-Linked/immunology , Humans , Immunoglobulins/blood , Immunoglobulins, Intravenous/therapeutic use , Male
9.
Allergol Immunopathol (Madr) ; 48(5): 424-429, 2020.
Article in English | MEDLINE | ID: mdl-32653225

ABSTRACT

INTRODUCTION AND OBJECTIVES: Considering that no studies have been done on a comprehensive review of Serum sickness-like reactions patients (SSLRs) at a referral center in Iran so far, this study aimed to determine the clinical and laboratory characteristics of children with SSRL in Tehran Children's Medical Center. PATIENTS: The present study was a registry-based study in which the data of 94 SSLRs patients registered in a two-year period were investigated. Confirmation of fever, rash, urticaria, arthralgia / arthritis and history of antibiotic consumption up to three weeks before were the criteria for the diagnosis. RESULTS: Fifty-one (54 %) patients were male with mean age of 56 ±â€¯30 months and there was no significant difference in the age of the two genders. The mean onset of symptoms before hospitalization were 3.8 ±â€¯2.7 days (1-14 days); this mean was significantly higher in males than in females (4.6 ±â€¯2.9 versus 2.9 ±â€¯1.7 days, P-value = 0.003). Among antibiotics, Co-amoxiclav and Cefixime antibiotics had the most frequency by 31 % and 33 %, respectively as the most important incidence factor of SSLRs. The mean duration of consumption of culprit medications in the incidence of SSLRs was 5.6 ±â€¯2.9 days with a range of 1-15 days. CONCLUSIONS: This study showed that among the antibiotics, Co-amoxiclav and Cefixime are more prevalent and a review of prescribing these two antibiotics for the treatment of the children's infections is essential if this finding is confirmed by other Iranian scholars.


Subject(s)
Anti-Bacterial Agents/adverse effects , Bacterial Infections/drug therapy , Serum Sickness/epidemiology , Amoxicillin-Potassium Clavulanate Combination/adverse effects , Cefixime/adverse effects , Child , Child, Preschool , Female , Humans , Incidence , Iran/epidemiology , Male , Prevalence , Registries/statistics & numerical data , Serum Sickness/etiology , Sex Factors
10.
Iran J Allergy Asthma Immunol ; 18(3): 340-345, 2019 Jun 08.
Article in English | MEDLINE | ID: mdl-31522441

ABSTRACT

Asthma is a common respiratory disease with huge economic burden leading to activity limitations, morbidity, and mortality. In this study, we aim to investigate the prevalence of Oppositional Defiant Disorder (ODD), Attention Deficit Hyperactivity Disorder (ADHD) and Conduct Disorder (CD) among children with asthma. This case-control study was performed in a pediatric referral health care center(Children's Medical CenterinTehran University of Medical Sciences) in 2017.With random selection, the 80 children with asthma and 92 controls with age range of 5 to 11 years were enrolled in this study. In addition to the demographic information and family history of allergy, asthma symptoms, and control quality evaluated with a validated Childhood Asthma Control Test (C-ACT). The mode of measurement for ADHD, ODD and CD was based on Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) psychiatric scales from clinical interviews conducted by child psychiatrists. Totally, 42.5% and 25% in the case and control groups had ADHD respectively withsignificant difference (p=0.01). Also, 25% and 5.4% in thecase and control groups had ODD respectively with significant difference (p=0.001). But conduct disorder was 10% and 10.9% in case and control groups respectively without significant difference (p=0.8). Children with asthma were associated with exhibiting ADHD and ODD but not CD. Therefore, appropriate evaluation and treatment are needed for asthmatic children with attention-deficit and ODD symptoms. Besides, further research is needed to determine the etiological approach towards ADHD, ODD and asthma.


Subject(s)
Asthma/complications , Asthma/epidemiology , Mental Disorders/complications , Mental Disorders/epidemiology , Adolescent , Asthma/diagnosis , Case-Control Studies , Child , Child, Preschool , Diagnostic and Statistical Manual of Mental Disorders , Female , Humans , Infant , Iran/epidemiology , Male , Mental Disorders/diagnosis , Prevalence , Public Health Surveillance , Respiratory Function Tests
11.
Mol Biol Rep ; 46(6): 6571-6575, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31520268

ABSTRACT

The recombination activating genes, including RAG1 and RAG2, are essential for V(D)J somatic recombination in lymphocytes. Leaky severe combined immunodeficiency disorder (SCID) is characterized by normal or intermediate T cells and normal to absent B cells associated with partial T cell and B cell dysfunction. We present a newly found RAG1 deficiency in a 21-year-old boy with leaky SCID. Immunoglobulin levels, flow cytometry, and whole exome sequencing (WES) were evaluated. Flow cytometric analysis revealed a decreased number of CD3+, CD4+, and CD8+ T cells, and B cells whereas NK cell counts were normal. Immunoglobulin levels were also decreased. The WES revealed a newly found homozygous mutation of RAG1 gene (NM_000448: exon 2: c.C2275T). Atypical features, including leukopenia, candidiasis, and low lymphocyte counts in patients with late-onset combined immunodeficiency disorders (CID) such as leaky SCID due to RAG1 deficiency may result in misdiagnosis and inadequate therapy instead of adopting the curative hematopoietic stem cell transplantation in these patients.


Subject(s)
Homeodomain Proteins/genetics , Mutation , Severe Combined Immunodeficiency/genetics , B-Lymphocytes/metabolism , Homozygote , Humans , Loss of Function Mutation , Lymphocyte Count , Male , Severe Combined Immunodeficiency/immunology , T-Lymphocytes/metabolism , Exome Sequencing , Young Adult
12.
Iran J Allergy Asthma Immunol ; 18(2): 225-229, 2019 Apr 01.
Article in English | MEDLINE | ID: mdl-31066259

ABSTRACT

Hyperimmunoglobulin E syndrome (HIGE) is considered as a phagocytic or a newly classified complex and heterogeneous primary immunodeficiency disease with symptoms such as increased levels of immunoglobulin E, eczema, and, recurrent lung and skin infections. In this paper, we have presented a rare case of this syndrome. A 9-year-old Iranian girl presented with a history of pruritic maculopapular rash who was eventually diagnosed as a case of HIGE. In her recent admission, she had dysphonia, stridor and huge cauliflower cutaneous lesions on her neck, finger and vocal cords, which did not respond to intravenous antibiotics, and ultimately required surgical removal.


Subject(s)
Guanine Nucleotide Exchange Factors/genetics , Herpes Simplex/diagnosis , Immunoglobulins, Intravenous/therapeutic use , Job Syndrome/diagnosis , Mutation/genetics , Simplexvirus/physiology , Skin/pathology , Vocal Cords/pathology , Anti-Bacterial Agents/therapeutic use , Child , Drug Resistance , Dysphonia , Female , Herpes Simplex/drug therapy , Humans , Immunoglobulin E/metabolism , Job Syndrome/drug therapy , Laryngoscopy , Respiratory Sounds , Skin/virology
13.
Scand J Immunol ; 90(1): e12767, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30963593

ABSTRACT

One of the components of NADPH oxidase is p47-phox, encoded by NCF1 gene. This study aims to find new genetic changes and clinical features in 38 Iranian patients with autosomal recessive chronic granulomatous disease (AR-CGD) caused by NCF1 gene defect. Patients who had abnormal NBT and DHR-1,2,3 assay with loss of p47-phox in Western blotting were included in this study. After recording demographic and clinical data, PCR amplification was performed followed by direct sequencing for all exons and exon-intron boundaries. The most common form of CGD in Iran was AR-CGD due to consanguinity marriages. Among patients with AR-CGD, NCF1 deficiency was found to be more common than other forms. Cutaneous involvements (53%), pulmonary infections (50%) and lymphadenopathy (29%) were more prevalent than other clinical manifestations of CGD. Mutation analysis of NCF1 gene identified five different mutations. Homozygous delta GT deletion (c.75_76delGT) was the most frequent mutation and was detected in more than 63% of families. Six families had a nonsense mutation in exon 7 (c.579G > A). Two novel mutations were found in exon 4 in two families, including a missense mutation (c.328C > T) and a nine-nucleotide deletion (c.331_339delTGTCCCCAC). Genetic detection of these mutations may result in early diagnosis and prevention of possible complications of the disease. This could be useful for timely decision-making for haematopoietic stem cell transplantation and for carrier detection as well as prenatal diagnosis of next children in the affected families. Our findings might help to predict outcomes, raise awareness and help effective treatment in these patients.


Subject(s)
Granulomatous Disease, Chronic/genetics , Lymph Nodes/pathology , Mutation/genetics , NADPH Oxidases/genetics , Respiratory Tract Infections/genetics , Skin/pathology , Adolescent , Adult , Child , DNA Mutational Analysis , Early Diagnosis , Female , Humans , Iran , Male , Polymerase Chain Reaction , Young Adult
14.
Pediatr Allergy Immunol ; 30(4): 469-478, 2019 06.
Article in English | MEDLINE | ID: mdl-30801830

ABSTRACT

BACKGROUND: Hyper-IgE syndromes (HIES) are distinct diseases characterized by recurrent cutaneous and lung infections, eczema, and elevated serum IgE level. METHODS: In this study, clinical manifestations, immunologic findings, and genetic studies of all patients with HIES in the Iranian national registry database were evaluated. RESULTS: A total of 129 HIES patients with a median age of 14.0 (9.0-24.0) years were followed up for a total of 307.8 patient-years. Genetic studies showed heterozygous STAT3 mutations in 19 patients and homozygous DOCK8 mutation in 16 patients. The mean of National Institutes of Health score in STAT3-deficient patients was higher than in patients with DOCK8 mutation (P = 0.001). It was shown that the presence of pneumatocele and hematologic complication were significantly frequent in STAT3-deficient cases compared to patients with DOCK8 deficiency (P = 0.001 and P = 0.002, respectively). Moreover, the median IgE serum levels were higher in patients with STAT3 gene mutation than in patients with DOCK8 gene mutation (P = 0.02). The eosinophils' count was enhanced in patients with DOCK8 deficiency than in patients with STAT3 gene defects (P = 0.02). CONCLUSION: Specific molecular study of STAT3 and DOCK8 mutations in patients with HIES clinical phenotype could help the physician to definitively characterize the disease. Since HIES showed the highest rate of unsolved combined immunodeficiency, investigation of other genetic and environmental factors could also help in understanding the mechanism of remaining patients as well as providing strategy into therapeutic modalities.


Subject(s)
Guanine Nucleotide Exchange Factors/genetics , Infections/epidemiology , Job Syndrome/epidemiology , Lung/pathology , Mutation/genetics , STAT3 Transcription Factor/genetics , Skin/pathology , Adolescent , Adult , Child , Cohort Studies , Female , Follow-Up Studies , Humans , Immunoglobulin E/blood , Infections/genetics , Iran/epidemiology , Job Syndrome/genetics , Male , Young Adult
16.
Clin Exp Hepatol ; 5(4): 285-288, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31893239

ABSTRACT

AIM OF THE STUDY: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease which could be associated with inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). The aim of this study was to compare GGT and IgG4 levels among children with UC with PSC and without PSC. MATERIAL AND METHODS: In this cross sectional study children with UC with PSC and UC without PSC were included. Serum immunoglobulin G4 (IgG4) and gamma-glutamyl transpeptidase (GGT) levels of the 90 UC patients with and without concomitant PSC were measured. Children with serum IgG4 concentration > 175 mg/dl were considered to have elevated IgG4. RESULTS: Elevated serum IgG4 was found in 8 of 30 (26.6%) patients with PSC vs. 3 of 60 (5.0%) patients without PSC. Compared with the group without symptoms of PSC, the group with PSC showed significantly higher levels of aspartate aminotransferases (AST; 22.5 U/l vs. 70.0 U/l, p < 0.001), alkaline phosphatase (ALP; 359.0 U/l vs. 602.0 U/l, p < 0.001), and IgG4 (56.0 vs. 73.0, p = 0.02). The odd ratio of the elevated IgG4 and GGT in predicting PSC was 6.9 (95% CI: 1.6-28.4) and 18 (95% CI: 5.7-55.9), respectively. CONCLUSIONS: AST, alanine aminotransferase (ALT), GGT, ALP, and serum IgG4 were significantly higher in UC patients with sclerosing cholangitis (SC) compared to UC patients without SC. GGT and IgG-4 measurements are recommended for evaluation of UC.

17.
J Allergy Clin Immunol Pract ; 7(3): 864-878.e9, 2019 03.
Article in English | MEDLINE | ID: mdl-30240888

ABSTRACT

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.


Subject(s)
Agammaglobulinemia , Common Variable Immunodeficiency , Hyper-IgM Immunodeficiency Syndrome , Adolescent , Adult , Agammaglobulinaemia Tyrosine Kinase/genetics , Agammaglobulinemia/genetics , Agammaglobulinemia/mortality , CD40 Ligand/genetics , Child , Child, Preschool , Common Variable Immunodeficiency/genetics , Common Variable Immunodeficiency/mortality , Diarrhea/genetics , Diarrhea/mortality , Female , Genetic Association Studies , Humans , Hyper-IgM Immunodeficiency Syndrome/genetics , Hyper-IgM Immunodeficiency Syndrome/mortality , Immunoglobulin mu-Chains/genetics , Male , Meningitis/genetics , Meningitis/mortality , Mutation , Poliomyelitis/genetics , Poliomyelitis/mortality , Severity of Illness Index , Young Adult
18.
J Clin Immunol ; 38(7): 816-832, 2018 10.
Article in English | MEDLINE | ID: mdl-30302726

ABSTRACT

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.


Subject(s)
Immunologic Deficiency Syndromes/epidemiology , Adolescent , Adult , Age Factors , Child , Child, Preschool , Disease Susceptibility , Female , Follow-Up Studies , Genetic Predisposition to Disease , Genetic Testing , Geography, Medical , Humans , Immunologic Deficiency Syndromes/diagnosis , Immunologic Deficiency Syndromes/etiology , Infant , Infant, Newborn , Iran/epidemiology , Male , Middle Aged , Molecular Diagnostic Techniques , Population Surveillance , Prevalence , Registries , Young Adult
19.
Electron Physician ; 10(2): 6327-6332, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29629055

ABSTRACT

BACKGROUND AND AIM: Standardized techniques help us to better diagnosis and follow up of allergic diseases. In this study, we determined the sensitivity, accuracy, and specificity of an Immunoblotting test compared to ImmunoCAP as the reference in vitro test for detection of specific IgE in allergic patients. METHODS: In this cross-sectional study, specific IgE level was determined in patients with allergic symptoms who referred to the Immunology, Asthma and Allergy Research Institute, Tehran, Iran from 2010-2016, by two techniques. Eleven different allergens (six aeroallergens and five food allergens) were determined, and 303 specific IgE tests were performed for the patients by each method. The Immunoblotting test is a multiplex assay on a nitrocellulose membrane coated with 20 selected allergens. ImmunoCAP is considered as the reference method for determination of in vitro specific IgE. Its principle is an automated sandwich immunoassay, and allergens were bound to the solid phase, covalently. Finally, the fluorescence of elute was determined. Specific IgE more than 0.35 KU/L was considered as a positive test. Sensitivity, specificity, accuracy, kappa coefficient, positive and negative likelihood ratio (+/- LR), and correlation coefficient (calculated with Spearman test) between two tests were determined using statistical analysis (SPSS software, version 18). RESULTS: One hundred and thirty five patients entered this study. The median age of the patients was 3.75 years with the males constituting 54.8% of the population. The most common cheif complaints were respiratory (51.6%), skin (41.8%) and gastrointestinal (27.9%) symptoms, respectively. The sensitivity, specificity, accuracy, +LR and -LR were 83%, 97%, 92%, 27.66 and 0.17, respectively. The kappa coefficient of the immunoblotting test was 0.81 compared to the reference technique. The correlation coefficient for positive tests between the two methods was 0.71 (p<0.001). CONCLUSION: Regarding the presence of 20 allergens in a RIDA allergy panel and according to our findings, this immunoblotting test with high sensitivity could be used as a fast and cost-efficient screening test. However, ImmunoCAP is recommended when the accurate level of specific IgE is required. ImmunoCAP findings are particularly helpful for immunotherapy and the elimination diet.

20.
Iran J Public Health ; 47(2): 256-263, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29445636

ABSTRACT

BACKGROUND: Asthma is the first cause of children hospitalization and need for emergency and impose high economic burden on the families and governments. We aimed to investigate the economic burden of pediatric asthma and its contribution to family health budget in Iran. METHODS: Overall, 283 pediatric asthmatic patients, who referred to two tertiary pediatric referral centers in Tehran capital of Iran, included from 2010-2012. Direct and indirect asthma-related costs were recorded during one-year period. Data were statistically analyzed for finding association between the costs and factors that affect this cost (demographic variables, tobacco smoke exposure, control status of asthma and asthma concomitant diseases). RESULTS: Ninety-two (32.5%) females and 191(67.5%) males with the age range of 1-16 yr old were included. We found the annual total pediatrics asthma related costs were 367.97±23.06 USD. The highest cost belonged to the medications (69%) and the lowest one to the emergency (2%). We noticed a significant increasing in boys' total costs (P=0.011), and 7-11 yr old age group (P=0.018). In addition, we found significant association between total asthma costs and asthma control status (P=0.011). CONCLUSION: The presence of an asthmatic child can consume nearly half of the health budget of a family. Our results emphasis on improving asthma management programs, which leads to successful control status of the disease and reduction in economic burden of pediatric asthma.

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