Iranian Journal of Allergy, Asthma and Immunology
Volume:19 Issue: 2, Apr 2020

Despite the importance of CD44 and CD133 in various cancers, the clinicopathological and prognostic values of these biomarkers in esophageal cancer remain debated. Hence, in this study, we did a meta-analysis to explore the correlation between overexpression of these markers and some clinicopathological features and their influence on the survival of esophageal cancer patients. A search in PubMed and Web of Science (among all articles published up to January 16, 2018) was done using the following keywords: esophageal cancer, CD44, CD133, prominin-1, AC133. Suitable studies, that were selected based on the criteria listed in the Materials and Methods section, were chosen and hazard ratios with 95% confidence intervals were estimated if available. Heterogeneity and sensitivity were also analyzed. Furthermore, publication bias was assessed using funnel plots, Egger, and Begg tests. The study included 1346 patients from 13 related studies. The median rates of marker expressions by immunohistochemistry were 35.7% (30%-76.6%) from 9 studies for CD44 and 31.9% (21%–44.2%) from 5 studies for CD133. The accumulative 5-year overall survival rates of CD44-positive and CD133-positive were 1.59% (1.22-2.06) and 1.27% (0.93-1.73), respectively. Meta-analysis showed that CD44 expression had a significant correlation with 5-year overall survival. CD44 overexpression showed a correlation with some clinicopathological features such as lymph node metastasis, vascular invasion, and recurrence of the disease, while it was not the case for coexpression of CD44 and CD133. In conclusion, CD44 overexpression was associated with a 5-year overall survival rate and thus this biomarker can be a suitable prognostic tool in esophageal cancer.

The advances in science and technology in recent decades, especially in medical sciences, have raised new ethical challenges. Hence, professional organizations in the field of medical science are trying to develop regulations in the field of medical ethics to help medical science professionals in making the best decisions in different circumstances and moral dilemmas. The organizations also try to monitor their performance using those regulations. On the other hand, due to the specialization of medical science as well as the complexity of communication between these disciplines, there is a growing need for regulations to answer questions and resolve the challenges of each discipline. Certainly, scientific societies, due to benefit from relevant specialists, are the best reference for the development of specialized guidelines, one of which is the Iranian Society of Asthma and Allergy (ISAA). The aim of the current study was to develop codes of ethics for ISAA members, using a qualitative study. Generally, the ISAA codes of professional ethics consists of general and specific sections. In order to compile the general section, the upstream medical documents, including the patients' rights charter in Iran, the research ethics guidelines approved by the Ministry of Health and Medical Education (MOHME), ethical codes from the international societies of asthma and allergy, the general codes of professional ethics of the Iran Medical Council and the Islamic jurisprudential rules and the statute law of the country were used. To develop specific sections, we interviewed the experts in the field of Asthma and Allergy about the ethical challenges they had ever faced with. The ISAA codes of professional ethics developed in five chapters, entitled "Ethical Guidelines for the Mangers and Director of the Society, General Guidelines, Specific Guidelines, Ethical Guidelines for Research and Education, and Procedure for Supervision on the Professional Behavior of the ISAA Members", and approved by the board of directors of ISAA.

IgE-mediated hypersensitivity reaction to pollens is a common health problem in atopic patients. In this regard, the assessment of the allergenicity of highly pollinating plants would be demanding. Based on the increment of Ailanthus altissima (A. altissima) tree in some parts of Iran and considering its probable role in respiratory allergy, in this study, we aimed to investigate its IgE-immunoreactivity and in diagnostic applications. One hundred and twenty-five allergic rhinitis patients who were diagnosed as high IgE responders and demonstrated seasonal rhinitis or rhinoconjunctivitis, as well as 20 healthy controls (HCs) with no allergic symptoms, were enrolled in this study. Total protein extract was prepared from A. altissima pollens and subjected to quality control experiments and finally used in ELISA and western blotting studies. Approximately 24% of the atopic patients (30 from 125) showed positive immunoreactivity to A. altissima extract. The median (IQR) of absorbance (450 nm) of the specific IgE against A. altissima pollen extract in HCs and positive groups were 0.33 (0.28-0.42) and 0.59 (0.36-0.79), respectively (p<0.001). Receiver operating characteristics (ROC) curve analysis of the specific ELISA results, revealed a cut-off value of 0.46 and a sensitivity of 70% and specificity of 100%. Western blotting with the sera positive cases revealed that the main immunoreactive proteins range from 10 to 70 kDa. This study revealed that some of A. altissima pollen proteins ranging from 10 to 70 kDa show IgE-reactivity in atopic patients and may play a role in their allergic reaction symptoms.

Allergy to non-specific lipidtransfer protein (nsLTP), the major allergen of grape (Vit v1), is considered as one of the most common fruit allergies in Iran. Therefore, a specific monoclonal antibody (mAb) can be used for the characterization and assessment of. Accordingly, this study aimed to generate and characterize a mAb against Vit v1 with a diagnostic purpose. To this end, Vit v1 allergen (9 kDa) was extracted using a modified Bjorksten extraction method. Natural Vit v1-immunized mouse splenocytes were fused with SP2/0Ag-14 myeloma cells for generating hybridoma cells. Specific antibody-secreting Hybridoma cells were selected using ELISA. Finally, anti-Vit v1 mAb was characterized by western blotting, ELISA, and isotyping methods. In the current study, a 9 kDa (Vit v1) protein was attained fromcrude and fresh juice of grape extracts and the isotype of desired anti-Vit v1 mAb was determined as IgM with k light chain. In addition, The ELISA results demonstrated that anti-Vit v1 mAb was specified against natural Vit v1 in the grape cultivar and related LTP allergens, such as Pla or 3 (p<0.0001). In the present study, a specific mAb was produced for detecting the LTP allergen. This mAb with a confirmed specificity can be utilized for evaluating the LTP allergens and their allergenicity in different grape cultivars.

Purification and preparation of three diagnostic antigens used for the detection of human T-lymphotropic virus (HTLV)-I/-II infection in E.coli are different parts of a multi-step method. In this study, our aim was to design a chimeric protein for the simultaneous detection of HTLV-I and HTLV-II antibodies. Immunodominant B cell linear epitopes of envelope and capsid proteins of HTLV-I/-II were selected and linked together; using a suitable amino acid linker and a chimeric antigen (CA). The codon-optimized synthetic DNA encoding the CA was subcloned into the pGS21aexpression vector and CA expressed as His-GST fused protein in E. coli BL21 (DE3) cells. Then the recombinant CA was purified, using the Ni-NTA (Nickle Nitrilotriacetic acid) affinity chromatography under native conditions. The Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and densitometric scanning results showed that CA accounted for 15% of the total cellular proteins and approximately 50% of the expressed histidine-glutathione s-transferase-chimeric antigen (His-GST-CA) proteins were soluble. The CA was successfully purified in one step with a purity of greater than 90%, which is suitable for antigenicity evaluations. Enzyme-linked immunosorbent assay (ELISA) results showed that the GST fused CA reacted in a concentration-dependent manner with HTLV-I/-II infected sera and was able to distinguish normal serum from HTLV-I/-II infected one with a proper sensitivity. With further validation, CA, as described in the present study could be introduced as a novel reliable, cost-effective and easy alternative for the three separate HTLV-I/-II diagnostic peptide antigens, which is prepared as a fusion with GST.

Staphylococcal enterotoxin B (SEB), apotent superantigen, is responsible for many disorders caused by Staphylococcus aureus. With regard to the appearance of multidrug-resistant strains of the bacteria, there is a great need to develop an efficient vaccine against this pathogen. In the present study, the immunogenicity of recombinant SEB was evaluated following nasal administration to BABLB/c mice. Indeed, the rSEB protein was entrapped into chitosan nanoparticles and the immunogenicity of nano-formulation was investigated. SEB protein was expressed in E. coli BL21 (DE3) and purified by using a nickel column. Chitosan nanoparticles were synthesized in the presence of rSEB; using the ionic gelation technique. Synthesized NPs containing rSEB and bare rSEB were administered to mice nasally. Serum and stool IgG and IgA antibody showed that both formulations were able to evoke the mice's immune responses and there was no significant difference between them. Results of the toxin neutralization test on Vero cells indicated that the sera of the immunized mice had an inhibitory effect on the growth of these cells (p<0.001). Nasal administration of bare rSEB could efficiently simulate the mice's immune system and nano-delivery of this protein via nasal route had not a significant impact on its immunogenicity improvement.

Previous studies have demonstrated that maturation of dendritic cells (DCs) by pathogenic components through pathogen-associated molecular patterns (PAMPs) such as Listeria monocytogenes lysate (LML) or CpG DNA can improve cancer vaccination in experimental models. In this study, a mathematical model based on an artificial neural network (ANN) was used to predict several patterns and dosage of matured DC administration for improved vaccination. The ANN model predicted that repeated co-injection of tumor antigen (TA)-loaded DCs matured with CpG (CpG-DC) and LML (List-DC) results in improved antitumor immune response as well as a reduction of immunosuppression in the tumor microenvironment. In the present study, we evaluated the ANN prediction accuracy about DC-based cancer vaccines pattern in the treatment of Wehi164 fibrosarcoma cancer-bearing mice. Our results showed that the administration of the DC vaccine according to ANN predicted pattern, leads to a decrease in the rate of tumor growth and size and augments CTL effector function. Furthermore, gene expression analysis confirmed an augmented immune response in the tumor microenvironment. Experimentations justified the validity of the ANN model forecast in the tumor growth and novel optimal dosage that led to more effective treatment.

Mouse model of multiple sclerosis (MS) is used for the inflammatory demyelinating disease. Rapamycin (RAPA) may contribute to the reduction of inflammatory responses to experimental autoimmune encephalomyelitis (EAE). Due to its adverse side effects, identifying new therapeutic agents is important. We investigated the transcriptional effects of evening primrose/hemp seed oil (EP/HS oil) compared to RAPA on the expression of immunological factors genes in spleen cells of EAE mouse models. We firstly induced EAE mice by injection of myelin oligodendrocyte glycoprotein (MOG). Then, the EAE mice treated and untreated with EP/HS oil were evaluated and compared with naïve mice. The spinal cords were examined histologically. The immunological factors including genes expression of the regulatory-associated protein of mammalian target of rapamycin (RAPTOR), regulatory-associated companion of mammalian target of rapamycin (RICTOR), interferon (IFN)-γ, interleukin (IL)-10, signal transducer and activator of transcription factors (STAT3), forkhead box P3 (FOXP3), and IL-17 of splenocytes were evaluated by real time-polymerase chain reaction (RT-PCR). The data showed that EP/HS oil was able to reduce the severity of EAE and inhibited the development of the disease. EP/HS oil treatment significantly inhibited the expression of RAPTOR, IFN-γ, IL-17, and STAT3 genes and promoted the expression of RICTOR, IL-10, and FOXP3 genes. In conclusion, the EP/HS oil is likely to be involved in transcription of factors in favor of EAE improvement as well as participating in remyelination in the EAE spinal cord and that it suggests to be effective in therapeutic approaches for MS.

The prevalence of primary immunodeficiency (PID) is rather high in Iran compared to the world average, mainly due to the high rate of consanguineous marriage. Despite that, little genetic information is available about primary immunodeficiencies in Iran. Autosomal recessive hyper IgE syndrome (AR-HIES) is a severe type of immunodeficiency, mainly caused by mutations in the dedicator of cytokinesis 8 (DOCK8). Rapid and precise diagnoses of patients suffering from AR-HIES can help to manage the patients and reach properly the treatment decision. However, in regions with low financial resources and limited expertise, deep phenotyping is uncommon. Therefore, an exome-first approach is helpful to make a genetic-based diagnosis. In the present study, whole-exome sequencing (WES) was applied to detect causative mutations in three unrelated primary immunodeficient patients with poor clinical information. One of the cases was a deceased patient with suspected hyper IgE syndrome (HIES) whose parents were subjected to WES. As a result, three novel pathogenic variants were detected in the DOCK8 gene, including two splicing sites (c.4241+1G>T and c.4886+1G>T) and one-stop-gain (c.4201G>T, p.Glu1401Ter) variants. Sanger sequencing confirmed the mutations’ segregation in corresponding families. Further immunological investigations confirmed that HIES in the studied probands. The presence of frontal bossing and broad nose in one of the studied cases, in addition to the typical clinical presentation of DOCK8-AR-HIES, is notable. This work suggests that an exome-first approach can be a valuable alternative strategy for precise diagnosis of primary immunodeficiency patients.

Occasionally, a seemingly straightforward history of food-induced anaphylaxis may prove to be misleading.  Both patients and their physicians have a tendency to attribute the cause of an allergic reaction to the most conspicuous ingredient that had been ingested while overlooking less likely causes.  Here, we describe a patient whose history pointed to oatmeal allergy, but skin prick tests to oats and serologic testing for oat-specific IgE were negative. Ultimately, we found that the oatmeal had been contaminated with an allergenic insect, Psocid of the order Psocoptera.