The effects of Fasciola hepatica recombinant proteins (peroxiredoxin and cathepsin L1) on Crohn's disease experimental model.

The immunomodulatory potential of the excretory-secretory (E/S) proteins of the helminths has been shown in previous investigations. This study evaluated the effects of the recombinants and excretory-secretory proteins of the Fasciola hepatica on induced colitis in Balb/c mice. The F. hepatica Recombinant proteins, Cathepsin L1 and Peroxiredoxin, and E/S proteins were intraperitoneally injected into the three mice groups as the case groups, while the control groups received PBS. Colitis was induced in mice by intraluminal administration of the 2, 4, 6-Trinitrobenzenesulfonic acid solution (TNBS). After 8 h, the case groups received the second dosage of the treatments, and it was repeated 24 h later. The immunological, pathological, and macroscopic changes were evaluated 3 days after colitis induction. The macroscopic evaluation revealed significantly lower inflammatory scores in the mice treated with recombinant Peroxiredoxin (rPRX) and recombinant Cathepsin L1 (rCL1). Despite the macroscopic observation, the pathological finding was insignificant between the groups. IFN-γ secretion was significantly lower in splenocytes of the groups that received rPRX, rCL1, and E/S than the controls. IL-10 showed significantly higher levels in groups treated with rPRX and rCL1 than controls, whereas the level of IL-4 was not statistically significant. Excretory-secretory proteins of the F. hepatica showed immunomodulatory potency and the main effects observed in this study were through the reduction of inflammatory cytokine and inflammation manifestation as well as induction of anti-inflammatory cytokines.

The Effect of Oral Montelukast in Controlling Asthma Attacks in Children: A Randomized Double-blind Placebo Control Study.

Oral Montelukast is recommended as maintenance therapy for persistent asthma, but there is controversy regarding its effectiveness in controlling asthma attacks. The present study was conducted to investigate the clinical efficacy of oral Montelukast for asthma attacks in children. This study was conducted as a double-blind placebo-controlled clinical trial on 80 children aged 1-14 years with asthma who were admitted to the emergency department of Bahrami Children's Hospital (Tehran, Iran) during one year. Patients were randomly divided into case and control groups. In addition to the standard asthma attack treatment, Montelukast was prescribed in the case group and placebo in the control group for one week. Patients were evaluated in terms of asthma attack severity score and oxygen saturation percentage (SpO2) in room air as primary outcomes 1, 4, 8, 24 and 48 hours after admission. In the first 48 hours, there was no significant difference in the score of asthma attack severity and SpO2 between the case and control groups. There was no significant difference between the groups in terms of length of hospitalization or number of admissions to the intensive care unit. None of the patients were re-hospitalized after discharge. The results of this study showed that the use of Montelukast along with the standard treatment of asthma attacks in children has no added benefit.

Association between IL-10 (at position -592) and IL-4 (at position -589) genotype polymorphism with atopic and non-atopic asthma in children.

OBJECTIVES: Asthma is the most prevalent respiratory disease, caused by chronic bronchial inflammation. Cytokines are known to play an important role in the pathophysiology of asthma. This study aimed to compare interleukin-4 (IL-4) and interleukin-10 (IL-10) gene polymorphisms between Iranian pediatric asthmatic patients and healthy controls and to investigate IL4 and IL10 gene variations in children with atopic and non-atopic asthma phenotypes. METHODS: In this prospective case-control study, a total of 95 unrelated pediatric asthmatic patients were recruited according to the Global Initiative for Asthma (GINA) criteria. The control group comprised two subgroups of 538 and 491 healthy individuals, undergoing IL4 and IL10 polymorphism assessments, respectively. The IL4 -589C/T (rs2243250) and IL10 -592A/C (rs1800872) gene polymorphisms were evaluated using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) assay. RESULTS: The findings indicated a significant difference in IL4 gene polymorphisms at position -589 between the asthmatic and healthy control groups. However, no significant difference was found in terms of IL10 gene polymorphisms, and they were not associated with atopy in the patients. CONCLUSION: The IL4 -589C/T polymorphism (rs2243250) can be a risk factor for asthma susceptibility, whereas the IL10 -592A/C polymorphism (rs1800872) is not a risk factor in the Iranian pediatric population. The results also showed that these polymorphisms are not risk factors for atopy in asthmatic children.

Tumor Necrosis Factor-α (-308G>A) Gene Polymorphism and Its Association with Asthma and Atopy Status.

Asthma is one of the most prevalent chronic lung diseases that afflict genetically predisposed individuals. Certain cytokine gene polymorphisms have been associated with asthma. Tumor necrosis factor-alpha (TNF-α) is a potent inflammatory cytokine that can modulate nonspecific inflammation to influence asthma. This study aimed to define the relationship between the TNF gene polymorphism at position -308 and asthma susceptibility, as well as atopic and non-atopic asthma. Using polymerase chain reaction with sequence-specific primers, we investigated genotype frequencies and alleles of a polymorphic gene coding for TNF-α in 86 pediatric patients with asthma and 470 healthy controls of the same race. Seventy-four patients underwent a skin prick test. The homozygous AA variant (-308, rs1800629) was the most common genotype among patients, accounting for 63.3% of all cases. In contrast, homozygous GG (-308) was significantly less prevalent in the patient group compared to the control group. TNF A (-308) allele frequency was 85.5% among asthma patients and 16.6% among healthy controls. The genotype and allele frequencies of TNF (-308 A>G, rs1800629) did not differ between atopic and non-atopic asthma. In conclusion, TNF (-308) AA and AG genotypes are associated with asthma susceptibility in Iranian children, although there was no significant difference in polymorphism between atopic and non-atopic asthma and no difference in asthma severity groups.

Clinical and immunological characteristics of 69 leukocyte adhesion deficiency-I patients.

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.

Health Status and Inconveniences of Asthmatic Children During the First Year of the COVID-19 Pandemic.

The Coronavirus Disease 2019 (COVID-19) pandemic has been the most significant health concern in recent years, with respiratory symptoms being the most prominent. In children, asthma is the most prevalent chronic disease. Due to the similarities between the symptoms of these two conditions, we sought to assess the general health status of pediatric patients with asthma and their COVID-19-related difficulties during the first year of the pandemic in Iran. We collected data for this study by administering a questionnaire to the parents of 200 children with asthma who were registered in the database of the Asthma Clinic at a tertiary medical center in Tehran, Iran. Forty-five (22.5%) of 200 patients were suspected of having COVID-19, 11 (24.4%) underwent polymerase chain reaction (PCR) testing, and 10 (90.9%) assays were positive. During the first year of the pandemic, 41 patients (20.5%) were referred to a medical center at least once, with 31.7% due to an asthma attack. One hundred eighty-nine patients (94.5%) reported an improved disease status than the previous year, and only 31 patients (15.5%) were using asthma-related medications such as Salbutamol. The estimated mean Asthma Control Test (ACT) scores for two age categories, 4-11 years and 12-18 years, were 25.55±2.27 and 23.28±3.31, respectively, indicating satisfactory disease control. In the majority of our study population, asthma control was acceptable. However, the pandemic caused a significant increase in the anxiety levels of patients and their parents.

Inherited ARPC5 mutations cause an actinopathy impairing cell motility and disrupting cytokine signaling.

We describe the first cases of germline biallelic null mutations in ARPC5, part of the Arp2/3 actin nucleator complex, in two unrelated patients presenting with recurrent and severe infections, early-onset autoimmunity, inflammation, and dysmorphisms. This defect compromises multiple cell lineages and functions, and when protein expression is reestablished in-vitro, the Arp2/3 complex conformation and functions are rescued. As part of the pathophysiological evaluation, we also show that interleukin (IL)-6 signaling is distinctively impacted in this syndrome. Disruption of IL-6 classical but not trans-signaling highlights their differential roles in the disease and offers perspectives for therapeutic molecular targets.

TLRs expression in canine mammary gland neoplasms: a pathological and molecular study.

TLRs are a class of PRRs that play a vital role in innate immunity. TLRs are expressed on immune cells and mammary epithelial cells. They can promote tumor growth, angiogenesis, invasion, and viability signaling. The current study aimed to test the correlation between histologic types and grades of neoplasms and TLRs gene expression levels. Twenty-one tissue samples of canine mammary neoplasms were stained with H&E. Then, it evaluated histologic type and grade according to the methods of Goldschmidt et al. and Peña, respectively. We established real-time PCR quantification assays to measure the mRNA abundances of TLRs in normal and neoplastic mammary glands. Profile pattern of TLR 1, 2, 3, 4, 5, 6, and 9 genes expression in canine mammary glands performed in 21 samples of mammary gland neoplasms and three non-neoplastic mammary gland samples from normal dogs. TLR 3, 4, and 9 mRNA overexpression were detected. In addition, tubulopapillary carcinoma grade II, SCC grade III, and carcinoma mixed type grade II demonstrated the highest relative TLR-3, and 9 mRNA expression levels. Complex carcinoma grade I, ductal carcinoma grade II, and anaplastic carcinoma grade II showed the highest relative TLR4 mRNA expression level. Although histopathological characteristics of tumors, including histologic type, grade, and inflammation, influenced TLRs mRNA expression level, such correlation was insignificant (P > 0.05).

Pigeon mite: An underdiagnosed cause of papular urticaria.

BACKGROUND: Dermanyssus gallinae, known as bird mite, generally lives on nestlings' featherless skin. Humans are accidentally infected, and itchy dermatitis is induced when the mites are unable to use birds' blood. The diagnosis is difficult due to the very small size and rapid movement of the mites, which make them hard to spot. CASE PRESENTATION: A 14-year-old male and his mother were referred to the allergy clinic complaining of a 2-week generalized itchy cutaneous papular lesion, unresponsive to antihista-mines, with the feeling of an insect moving on the surface of the skin. Due to the history of recently hatched pigeons nesting on their balcony and finding very small bugs, diagnosed as D. gallinae, they were instructed to clean the pigeon's nest as the source of these parasites, which successfully solved the problem. CONCLUSION: Bird mite infestation should be considered in the differential diagnosis of recurrent pruritus and urticaria, refractory to conventional treatments. Physicians should be aware of this mite infestation in approach to any patient with papular urticaria.

Pulmonary Delivery of Levamisole Nanoparticles as an Immunomodulator Affecting Th and a Potential ADAM10 Inhibitor to Ameliorate Severe Allergic Asthma.

Asthma is a common chronic lung disease without absolute treatment, and hypersensitivity reactions and type 2 immune responses are responsible for asthma pathophysiology. ADAM10 as a metalloproteinase transmembrane protein is critical for development of Th2 responses, and levamisole as an anthelmintic drug has immunomodulatory effects, which not only regulates ADAM10 activity but also can suppress the bone marrow and neutrophil production. Therefore, in the present study, nanoparticles were used as a levamisole delivery system to reduce bone marrow suppression, and the immunomodulatory and ADAM10 inhibitory effects of levamisole were studied in allergic asthma. Asthmatic mice were treated with PLGA-levamisole nanoparticles. Then, AHR, BALF, and blood cell counts, levels of the IgG1 subclass, total and OVA-specific IgE, IL2, IL-4, IL-5, IL-10, IL-13, IL-17, IL-25, IL-33, INF-γ, and TNF-α, gene expression of FoxP3, T-bet, RORγt, PU.1, GATA3, FcεRII, CysLT1R, eotaxin, and ADAM10, and lung histopathology were evaluated. PLGA-LMHCl with considered characteristics could control airway hyper-responsiveness, eosinophils in the BALF, levels of immunoglobulins, Th2-, Th9-, and Th17-derived cytokines and pivotal genes, eosinophilic inflammation, hyperplasia of the goblet cell, and hyperproduction of mucus and could increase Th1- and Treg-derived cytokines and also pivotal genes. It could also modulate the ADAM10 activity and had no effect on the number of neutrophils in the bloodstream. The novel safe nanodrug had no side effect on the bone marrow to produce neutrophils and could control the allegro-immuno-inflammatory response of asthma.

The Efficacy of a New Protocol of Oral Immunotherapy to Wheat for Desensitization and Induction of Tolerance.

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.

Rare clinical presentations of hyper-IgE syndrome in a patient with dental abnormalities: A case report.

Asthma and anaphylaxis are two atypical presentations of hyper-IgE syndrome (HIES). Early diagnosis and management of HIES can improve quality of life of patients through minimizing orthodontic problems and other complications related to this disorder.

Invasive Rasamsonia argillacea infection in chronic granulomatous disease: Report of a new case and literature review.

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.

Delay in Diagnosis of Two Siblings with Severe Ocular Problems and Autoimmune Polyglandular Syndrome.

Autoimmune polyendocrine syndrome type 1 (APS1) is a scarce polyendocrinopathy with autosomal recessive inheritance results from defects in the human autoimmune regulatory (AIRE) gene. In addition to three major manifestations of APS1 including mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease, ophthalmic problems such as keratoconjunctivitis, dry eye, iridocyclitis, and cataract can be seen in these patients. In this article, we introduced two siblings presented with nail dystrophia, severe photophobia, and keratitis since early childhood which genetic examination revealed single nucleotide T>C translocation in their 2nd exon and heterozygous deletion mutation in their 12th exon.

Serum sickness-like reactions in Iranian children: a registry-based study in a referral center.

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.

Molecular Characterization of Fasciola spp. from Some Parts of Iran.

BACKGROUND: Identification of liver flukes, Fasciola hepatica, and Fasciola gigantica by morphometric parameters is not always reliable due to the overlapping measurements. This study aimed to characterize the liver flukes of animals from different parts of Iran by the genetic markers, ITS1, and COXI. METHODS: We collected flukes from infected livestock in six provinces of Iran from Sep to Nov 2016. The flukes were identified by amplification of a 680 bp sequence of ITS1 locus followed by a restriction fragment polymorphism (RFLP) assay. The genetic diversity among isolates was evaluated by amplification and sequencing of a 493 bp fragment of the COXI gene. RESULTS: We obtained 38 specimens from Khuzestan, 22 from Tehran, 10 from Isfahan, 10 from Mazandaran, 4 from Kurdistan, and 3 from Ardabil provinces. PCR-RFLP analysis revealed two patterns, representing F. hepatica, and F. gigantica. Fifty specimens from cattle and sheep exhibited F. hepatica pattern and 37 from the cattle, sheep, buffalo, and goat that of F. gigantica. The phylogeny based on COXI revealed two distinct clades separating F. hepatica from F. gigantica. In our phylogeny, the Iranian F. gigantica isolates showed a distinct separation from the African flukes, while grouped with the East Asia specimens demonstrating a common ancestor. The F. hepatica isolates clustered with the flukes from different parts of the world, including East Asia, Europe, and South America. CONCLUSION: The present study revealed a substantial genetic difference between F. gigantica populations of Asia and Africa, while F. hepatica isolates from different parts of the world shared high similarities.

Esophageal-Crop Capillariasis and Proventriculus Ventriculus Hystrichisiasis in a Migratory Duck (Anas crecca).

BACKGROUND: The aim of the present study was to study pathological and parasitological characteristics of simultaneous capillariasis and hystrichiasis in a diseased Anas crecca captured in Mazandaran Province of Iran on Oct 2016. METHODS: Parasitology and histopathology techniques were used to detect the parasites of the carcass of the captive common teal. RESULTS: Macroscopically, severe chronic inflammatory reactions and nodular or granuloma formation and irregular thickening of the affected wall of the esophagus, crop, proventrculus and ventriculus were observed. Microscopically, apart from the chronic inflammatory reactions and granuloma formation, in the paraffin sections stained with Harris Hematoxyline and Eosin technique, the characteristics of the mature female and male Capillaria spp. and their barrel-shaped operculated embryonated eggs were found within the tunnels burrowed by the nematode in the hyperplastic stratified squamous epithelium of the inflamed crop and distal portion of the esophagus. The mature female Hystrichis spp. containing oval-shaped, embryonated non-operculated eggs and male parasite were found within the labyrinthus spaces formed in the submucosa granulomas of the ventriculus and proventriculus. CONCLUSION: Based on the parasitological and pathological studies, the species of the nematode parasites were identified as Capillaria (Thominx) contorta and Hystrichis. tricolor.

Associations of Behavioral Disorders with Asthma in Iranian Children.

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.

A Rare Case of Hyper IgE Syndrome with Vocal Cords Involvement.

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.

The first cohort of Iranian patients with hyper immunoglobulin E syndrome: A long-term follow-up and genetic analysis.

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.