Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 11th International Conference on Allergy, Asthma & Clinical Immunology Edinburgh, Scotland.

Day 2 :

Conference Series Allergy-Clinical Immunology 2017 International Conference Keynote Speaker Hikmet Jamil photo
Biography:

Professor Jamil received his medical degree from Baghdad University. He holds several postgraduate degrees from England. In 1979 joined Baghdad University, then in 1998 joined Wayne State University and in 2015 joined Michigan State University. He has published 20 books and 191 field research articles. He is one of the founders of "The International Society of Iraqi Scientists" in 2000 and “The AlNahrain International Society of Iraqi Scientists in 2017. Elected in 2002 as President of International Society of Iraqi Scientists until 2015. Professor Jamil received the Teacher Award from Wayne State University in 2006, 2010 and in 2013. 

Abstract:

Background: Gulf war 1991 (GW) syndrome is defined as a group of illnesses including allergy. Although it has been over than two decades since GW, more research is needed to address the impact of GW chemical (Ch) & GW non-chemical (NCh) environmental exposures on the health of Iraqis. The Ch & NCh are the two main etiologies that could explain the high rate of medical conditions, including allergy. However, in 2015, 30 % of adults & 40 % of children in the US reported allergy.

Objective: (1) To examines the prevalence rate of allergy among the study population at different war zone location, (2) To predict risk factors for each type of allergy studied, and self-rated health of Study population, (3) To explore the impact of Ch & NCh agents on different types of allergy & its relation to war zone location.

Methods: In 2002, a cross-sectional study of 1155 Iraqis males, age 18-45, who were residents within 300 Km from GW-1991 were studied. Resident physicians from Basrah University, were trained to implement a structured interview with the participants. The study population were those who accompanied the patients who attend any of the three government outpatient clinics at two provinces general hospitals, which are free of charge to all people. The study population were classified into three zones according to their location during the GW: war zone (Within 100 Km of Kuwait), zone 2 (within 100-190 Km) & zone 3 (within 200-300 km). The study questionnaires include different types of Allergy and the participants was asked to answer yes or no for the following allergies: (1) pre-asthma symptoms (2) rhinitis (3) skin allergy (4) eye allergy (5) chemical sensitivity allergy and (6) other allergy (could be food, drug etc.). For Ch exposures, participants were asked if during the GW they had direct contact with certain exposures: E.g. petrochemical fuel. For NCh exposures the questions included: E.g. missiles exploding. Different statistical tests were used through SPS version 22.

Results: Study results showed a significant difference in the prevalence of allergies (combined or separated) except for eye allergy by different zones (higher in war zone). Regarding type of allergies, the highest rate was rhinitis (36.2%) and the lowest was chemical sensitivities (2.4%). There was difference in the prevalence rate of allergy when testing their demographic variables at different war zones (higher at war zones). The results identified the predictor risk factors for each type of allergy, in which some of them were related to Ch or NCh. 22.1% of the study population who lived in war zones reported their current health was fair to poor, compared to 8.6% among those who were in zone 3.

Conclusion: There were significant differences between the location of participants during the GW-1991 in relation to different types of allergies. Those who reported excellent heath were: younger age, less years in army, hold high school or above, labor work, never smoke, have low scale of allergy and did not exposed to Ch or NCh.

Keynote Forum

Anil Mishra

Tulane University School of Medicine, USA

Keynote: Interleukin (IL)-15 immunotherapy a novel non-steroidal approach to treat allergen-induced airway obstructions

Time : 10:35-11:10

Conference Series Allergy-Clinical Immunology 2017 International Conference Keynote Speaker Anil Mishra photo
Biography:

Anil Mishra is a Professor of Medicine. He is also the Director of Tulane Eosinophilic Disorder Center in the Section of Pulmonary Diseases at Tulane University School of Medicine. His research established that eosinophils are the resident cells of the gastrointestinal tract that home prenatally. He showed that eosinophil active chemokine eotaxin-1 constitutively expressed and has significant role for eosinophils homing into the gastrointestinal tract. He developed the first murine model of eosinophilic esophagitis (EoE). His findings implicated aeroallergen in the etiology of EoE and suggested that esophageal eosinophilic inflammation is mechanistically associated with pulmonary inflammation. Recently, he reported that rIL-15 is a therapeutic molecule for the allergen-induced airway hyperactivity and fibrosis for chronic asthma and other pulmonary functional impairment. He is an elected fellow of American Academy of Allergy Asthma Immunology (FAAAAI) and American Gastrointestinal Association (FAGA). He has published over 72 articles, book chapters and reviews on molecular mechanisms of pulmonary and gastrointestinal allergic responses in high impact factor journals. His research is supported by National Institutes of Health via NIDDK and NIAID institutes. He is also a member of several NIH study sections and serving as Editor and Editorial Board Member in a number of international journals.

Abstract:

Allergen-induced airway obstruction is a physiologic feature of asthma and IL-15 deficiency is reported in asthmatic patients. Therefore, we tested the hypothesis that regulation of IL-15 is critical for the preservation of allergen-induced airway hyper responsiveness (AHR), airway resistance and compliance. Accordingly, airway inflammation, AHR, resistance and compliance were assessed in IL-15- gene deficient mice and IL-15 overexpressing mice in an allergen-induced murine model of asthma. Herein, we report that IL-15 deficiency promotes baseline airway resistance in naïve mice. Moreover, rIL-15 delivery to the lung down regulates expression of proinflammatory cytokines, and improves allergen-induced AHR, resistance and compliance. These observations were further validated in DOX-inducible CC-10-IL-15 transgenic mice. DOX exposed Aspergillus extract challenged CC-10-IL-15 bi-transgenic mice exhibited significantly reduced levels of pro inflammatory cytokines (IL-4, IL-5, IL-13) and decreased goblet cell hyperplasia. Airway obstruction including AHR and resistance was diminished in allergen challenged DOX exposed mice compared to non-DOX exposed CC-10-IL-15 bi-transgenic mice. Mechanistically, we observed that IL-15-mediated protection of airway obstruction is associated with induced IL-10-producing regulatory CD4+CD25+Foxp3+ T cells. Additionally, we found that a human IL-15 agonist (ALT-803) improved airway resistance and compliance in an experimental asthma model. Taken together, our studies conclude that IL-15 has a potent inhibitory effect on the airway obstruction that occurs in response to environmental allergens.

  • Asthma: Immunopathology
    Immunotherapy
    Skin Allergy
    Asthma
    Allergy Prevention, Risk Factors & Treatment
Location: Macallan Glenfiddich

Session Introduction

Michael Roth

University Hospital Basel, Switzerland

Title: Pre-disposition to asthma by epigenetic imprinting of mitochondria activity

Time : 11:30-11:55

Speaker
Biography:

Michael Roth is currently working as Head of Pulmonary Cell Research at University Hospital Basel, Switzerland. He has completed his PhD at University of Basel and worked as a Visiting Professor and Associate Professor at University of Sydney for two years. He has published 148 articles in reputed journals.

Abstract:

Chronic inflammatory lung diseases (CILD) are increasing worldwide and represent a major issue for daily life performance and public health expenditure. The two major CILD are asthma and chronic obstructive pulmonary diseases (COPD). The World Health Organization estimates that 280 million people suffer from asthma and 40% of all children suffer from asthma symptoms during childhood. According to the World Health Organization, 65 million people developed severe COPD with a death toll of 3 million/year in 2005. The likelihood to develop asthma or COPD was linked to inherited susceptibility factors; however, despite of large genetic cohorts, no specific candidate genes had been identified. Increasing evidence supports the hypothesis that the susceptibility to develop CILD is the consequence of exposure to risk factors during embryogenesis or early childhood. One of these factors is preterm birth which accounts for life-long reduced lung function due to incomplete maturation of the lung structure. Secondly, the exposure to fine dust, ozone, smoke particles, or viral infections early in life increases the risk to develop CILD, but the mechanisms that cause these largely irreversible modifications of lung structure and function are not well understood. Importantly, new studies in humans and animal models suggest that these pre-conditions for CILD susceptibility can be passed on over at least three generations. It is implied that the increased susceptibility for CILD is due to largely irreversible epigenetic modifications which may mimic a genetic trait. The available data points towards an epigenetic mechanism that involves mitochondrial genes rather than the human genome, which may explain why the inheritance of CILD susceptibility was linked to the maternal line. This review summarizes the knowledge supporting the hypothesis of an epigenetic rather than genetic event which underlies the inheritance of asthma and COPD susceptibility.

Gilberto Filaci

University of Genoa, Italy

Title: Telomerase cancer vaccines

Time : 11:55-12:20

Speaker
Biography:

Gilberto Filaci is an Associate Professor of Internal Medicine and Vice-Director of the Centre of Excellence for Biomedical Research at University of Genoa. He has published more than 90 papers in reputed journals and has been serving as Official Reviewer for international journals and research funding organizations. His scientific activity is mainly focused on Immuno-regulation and on the search for new diagnostic and immunotherapeutic agents. He is in the advisory board of pharmaceutics industries.

Abstract:

Telomerase, the enzyme synthesizing the telomeric regions of chromosomes, is considered as a universal tumor associated antigen because it is expressed by the majority of cancers. The several clinical trials performed adopting telomerase as immunogen confirmed the safety of telomerase vaccination, but raised doubts concerning: the immunogenicity of telomerase; the capacity of telomerase vaccines of inducing clinical responses. The immunogenicity concerns have been now dispelled by demonstrations that: Telomerase is presented by tumor and antigen presenting cells; ex vivo generated telomerase-specific CTL kills efficiently telomerase-expressing tumors; circulating telomerase-specific T cells are present in 90% of cancer patients and, surprisingly, in 100% of healthy individuals, as observed in studies. These findings boost the search for a new generation of telomerase vaccines able to overcome the limits of their first generation. In this effort, our group recently completed a phase I/II trial in prostate and renal cancer patients with GX301, a new generation cancer vaccine. This multi-peptidic vaccine includes four telomerase peptides, which bind promiscuously several HLA class I and II alleles allowing the coverage of the majority of HLA haplotypes and the induction of both helper and cytotoxic T cell responses. It also contains two adjuvants with complementary activities, making it able to efficiently activate both innate and adoptive immune responses. The results of a phase I/II trial, showing a 100% rate of telomerase-specific immune responses associated with evidences of clinical responses, suggest that innovative approaches may lead telomerase (and cancer) vaccination to an age of maturity.

Speaker
Biography:

Chiaki Masuda is a licensed Pharmacist and pursuing her Doctoral degree at Tohoku Medical and Pharmaceutical University, Japan. She has been working on “Analyzing differences in the pathophysiology of allergic asthma between sexes, focusing on the molecular mechanisms underlying the sex-specific effects of dendritic cells”. Her focus is primarily on translational research such as conducting basic immunological studies using mouse models and applying the results obtained in studies of the etiology of asthma in humans.

Abstract:

Statement of the Problem: Prevalence and severity of asthma symptoms after puberty are higher in women than in men. The numbers of IL-13-producing peripheral blood T cells are significantly higher in female than in male patients of atopic asthma. These T cells accelerate the female-predominated Th2-oriented immune response in asthma. The uptake and processing of inhaled allergens by dendritic cells (DCs) are fundamental for sensitization and subsequent elicitation of allergic airway responses. Observational data have suggested that DCs rapidly accumulate in the lamina propria in patients with allergic asthma after allergen challenge. However, the mechanism of DC involvement in the female-predominant Th2 immune responses in asthma is unclear.

Methodology & Theoretical Orientation: Male and female wild-type (WT) mice were sensitized using two intraperitoneal injections of ovalbumin (OVA) and aluminum hydroxide, followed by exposure to OVA aerosol challenges for 1 h on two occasions 4 h apart or administration of OVA intra-tracheal challenge. Here, we investigated the role of two major subsets of DCs in mice, CD11bhi and CD103+, in the orientation of T cells toward a Th2 phenotype observed predominantly in female patients of asthma.

Results: CD11bhi and CD103+ DC numbers in bronchial lymph nodes in female mice present a significant increase, measured 16 h after OVA challenge, compared to those in male mice. Additionally, CD103+ DCs in females expressed higher CD86 levels and had a higher potential of driving antigen uptake and Th2-cell differentiation compared to those in males. In contrast, such differences between the sexes were not observed for CD11b+ DCs.

Conclusion & Significance: These results suggest that the increased number of DCs and specific properties of CD103+ DCs may be involved in the Th2 immune response observed predominantly in female patients of allergic asthma.

Dana M. Tofiq

College of Medicine-University of Sulaimani, Iraq

Title: Assessment of the role of intrleukin-23 in ankylosing spondylitis

Time : 12:45-13:10

Speaker
Biography:

Dana M Tofiq is assistant professor of allergy and immunology and the academic registrar of the college of medicine-university of Sulaimani, Sulaymaniyah, Iraq; member of AAAAI, ACAAI and EAACI and working as part-time consultant allergist at Sulaymaniyah allergy and asthma center. He is teaching allergy and immunology to both undergraduate and postgraduate students at the college of medicine-university of Sulaimani. His research areas of interest include asthma, allergic and autoimmune diseases.

Abstract:

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting spine, sacroiliac joint and less frequently peripheral joints. Although, there is a strong hereditary component marked by the strong association with HLA-27 in more than 85% of patients with AS; the pathogenesis of AS is still not fully understood. Some inflammatory cytokines also play major role in AS pathogenesis. IL-23 regulates Th17 function, proliferation and IL-17 production which promote inflammation and bone and cartilage destruction when expressed chronically and in inappropriate locations.

Objectives: To assess serum IL-23 level in AS patients and controls and its association with disease activity.

Patients & Methods: 45 AS patients and 45 apparently healthy controls included in this cross sectional study. Other than comparing serum IL-23 level in AS patients with controls; we compared serum IL-23 level in AS patients on biologic with those non-biologic treatment. Assessment of disease activity was done by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and spinal mobility by Bath Ankylosing Spondylitis Metrology Index (BASMI) for any association with serum IL-23 levels.

Results: Serum IL-23 levels were significantly higher in AS patients in comparison with healthy controls and patients on biologic therapy had lower levels of IL-23 level than those patients on non-biologic therapy. In the AS patients, the BASDAI and BASMI scores had no correlation with serum IL-23 level.

Conclusions: Higher serum IL-23 levels in AS patients reflect the role of IL-23 in the pathogenesis of AS; and the future potential role of IL-23 in practice as both a biomarker and therapeutic target.

Mona Radwan (1), Hikmet Jamil (2), Thamer Hamdan (3), Taghreed Alnoor (4) and Nadia Alnoor (5)

1 Zagazig University, Egypt, 2 Michigan State University, USA, 3 University of Basra- Iraq, 4 College, University of Baghdad Ibn- Al Haitham, Baghdad, Iraq., 5 College of Science, Al-Mustansiriyah University, Baghdad, Iraq

Title: Impact of chemical and non-chemical agents on respiratory system including asthma among Iraqi people

Time : 13:10-13:35

Speaker
Biography:

Mona Radwan has completed her PhD from Zagazig University and Post-doctoral studies from Lund University School of Medicine and School of Social Sciences, respectively. She is one of the steering committee members of Women IN Great Sciences (WINGS) at Lund University. She has published various articles in reputed journals and has been serving as an Editorial Board Member of repute.

Abstract:

Introduction: Asthma is marked by reversible airway obstruction and airway inflammation. People with asthma demonstrate symptoms such as wheezing, coughing, and exertional dyspnea—that are accompanied by greater airflow obstruction. Chronic bronchitis is described by chronic cough and sputum production. Pulmonary emphysema (commonly mentioned to as emphysema) is a pathologic course including air-space expansion distal to the terminal bronchioles, accompanied by destruction of the bronchiolar walls. COPD includes chronic bronchitis and emphysema.

Objective: Objectives of the study were to find out: The prevalence rate of asthma and other lung disease in general and by different sub-categories of populations that exist at different distances from war zone; predictive risk factors for asthma and other lung diseases and; the impact of chemical (Ch) and non-chemical (NCh) agents on different kinds of lung diseases in relationship to diverse war sectors.

Methods: A cross-sectional study constructed on a sample of 1155 Iraqis who survived in the Basra and Messan (South of Iraq) Provence in 2002. Only males were recruited in the study with the ages of 18–45 years and were within 300 Km of the epicenter of the 1991 GW. The study population were assigned to one of three GW exposure zones, based on where they were located during the 1991 GW, as follow: zone one (war zone within 100 Km of Kuwait), zone two (within 100-190 Km) and zone three (within 200-300 Km).

Results: The study results showed that 50.8% of study populations were in zone three and 14.5% in zone one. There was a significant difference in the prevalence rate of asthma in general across the three war zones: highest in zone one (9.8%) compared to zone two (1.8%), and 5.8% in zone three. The significant difference also applied to other lung diseases; pneumonia, bronchitis and other lung conditions studied. As to bronchitis, the highest rate was among zone one (27.2%) and the lowest among zone three (9.4%). The results identified the predictor risk factors for asthma as those of lived in zone two, with high BMI and higher income. All asthmatic, bronchitis, pneumonia and other lung diseases inhaled smoke from fired oil wells while there was no significant effect on exposure to non-chemical factors like hearing chemical alarms or any dead bodies.

Conclusion: The study concludes some risk factors for asthma and other lung diseases.

Mabel Fabiola Ramallo Jadue

University of Saint Francis Xavier, Bolivia

Title: Vitamin D and skin atopic diseases

Time : 13:35-14:00

Speaker
Biography:

Mabel Fabiola Ramallo Jadue is a Physician Surgeon specialist in Dermatology-Immunopathology and Allergy. She is a Professor and Chair of Dermatology-Immunoalergologia, Faculty of Medicine at University of Saint Francis Xavier. She has been the member of the Bolivian Society of Dermatology & Internal Medicine, Sucre Branch since 2002. She is also the member of International Society of Dermatology and member of European Academy of Allergy and Clinical Immunology.

Abstract:

Vitamin D is well known for its major role in the intestinal, skeletal, kidney and parathyroid mechanisms for homeostasis of calcium and phosphorus. Recently, vitamin D has acquired an important role as immunoregulator of biological functions. There is also revised effect of vitamin D in both chronic urticarial and atopic dermatitis. Aim of this study is to evaluate the effects of prenatal and postnatal preventive use of vitamin D in the development of skin diseases in the new-born such as atopic dermatitis. Rueter et al., (published in 2014) given an expert opinion reviewing the impact of in utero and postnatal vitamin D exposure on allergy risk in childhood. Authors concluded that low cord blood 25-hydroxyvitamin D levels may be associated with increased risk of eczema and wheeze but not asthma and allergic rhinitis. For respiratory allergic disease outcomes, several studies have reported reduced wheeze or asthma later on during childhood or allergic rhinitis in offspring when maternal intake of food-derived vitamin D in pregnancy was reportedly higher. For eczema, consumption during pregnancy of food containing vitamin D was protective against symptoms in the first two years of life. Currently, the evidence with regard to the influence of vitamin D status (affected by both diet and lifestyle) on the development of allergic disease is limited and conflicting. The majority of studies have failed to show any consistent associations between 25(OH)D levels and subsequent allergic disease. Others propose supplementing infants with vitamin D for reducing the risk of asthma and allergic diseases. It is difficult to determine the low serum vitamin D levels contributed to the development of AD, whether damage of skin from AD led to low vitamin D absorption from the sun, or if the two are unrelated.

  • Video Presentation
Location: Macallan Glenfiddich
Biography:

Rebecca Heath is a UK trained medic who has worked in the Manchester, Melbourne, the Nepali Himalayas and Ghana before her interest in rural and remote medicine and Aboriginal health found her at home in the Red Desert of Alice Springs for a couple of years before heading to Papua New Guinea in the Pacific to teach Emergency Medicine and work on capacity building programs in Madang. Keen to help find ways to develop practical and useful strategies to update practice in low income settings, as well as understand some of the complex challenges these contexts provide, she has focused on asthma, which is notoriously poorly managed in the Pacific. 

Abstract:

Objective

To implement evidence based practice guidelines using a culturally sensitive change management approach and improve asthma management in a developing world setting.

Methods

Setting: Emergency Department, Modilon hospital, Madang, Papua New Guinea. Nearly 700,000 people live in Madang Province and Modilon Hospital (with 258 beds) is the only government hospital in the region. Study Design: 1) Asthma management analysis: A questionnaire was completed by Emergency Department staff during consultations with known asthma patients consisting of patient demographics, departmental and discharge management. Results were compared to international evidence based guidelines.  2) Action research with program change model: An action research approach using a 4 step model of program change (exposure, adoption, implementation and practice) was adopted with staff education and consultation to design and implement a new departmental asthma guideline. Culturally sensitivity and flexibility were maintained throughout. 3) Asthma management analysis: 3 months after the guideline implementation asthma management was re-analysed in the form of a questionnaire and results compared to original management. A ‘post mortem’ questionnaire was also conducted with staff to review progress and inform practice learnings. Outcomes measured: Treatment in line with evidenced-based asthma management guidelines, patient perception of treatment and frequency of Emergency department visits. Staff perceptions of treatment change outcomes and approach in managing the clinical changes.

Results: Prior to intervention, asthma management involved frequent use of IV and oral antibiotics, IV steroids, paracetamol, simultaneous use of multiple short acting oral bronchodilators, limited use of oral steroids (of variable dose and duration) and no spacers, preventative steroid inhaled therapy, or asthma action plans. At 3 months staff felt the program improved asthma management. Data is still being collected.

Conclusion: A 4 step model of program change was used to develop and implement asthma treatment guidelines. 

  • Poster Presentations
Location: Academy Breakout Lounge
Biography:

Abstract:

Statement of the Problem: Nasal irrigation with saline solutions is frequently used for relief of rhinitis symptoms. Literature suggests that manganese (Mn) contributes to a decrease in allergic nasal response. In vitro research studies were conducted on 3D model of airway epithelium to evaluate efficacy and safety of a Mn-enriched seawater solution called Stérimar Allergic Nose (SAN).

Methodology: The 3D Reconstituted Human Nasal Epithelium model (RHNE) was treated with 10 μL of SAN twice a day for four days to simulate repeated use (full strength) or untreated (control). For epithelium integrity (safety), the control and SAN-treated cultures were analyzed for: Trans-Epithelial-Electrical-Resistance (TEER) on days 1 (D1) and 4 (D4) post-treatment, and release of Lactate Dehydrogenase (LDH) and Interleukin 8 (IL-8) daily from D1 to D4. For efficacy, Mucociliary Clearance (MCC) and stimulation of epithelium-regeneration were assessed. MCC was measured by video-microscopy on D1 and D4 after the same treatment regimen. For epithelium-regeneration, RHNE was treated with 30 μL of SAN or saline. After a glass capillary injury, made 1 hour after treatment, regeneration stimulation was assessed as a percentage of wound closure by comparative photography immediately after the injury and 2, 6, 22 and 30 hours later.

Findings: SAN showed an average TEER of 302 and 323 ohm.cm2 (p<0,001) on D1 and D4, respectively, safely above tissue integrity limit (100 ohm.cm2). LDH and IL-8 releases were similar for SAN and control at all-time points, also confirming epithelium integrity and safety. SAN showed a significant MCC increase as compared to control (P<0.01). Furthermore, SAN showed faster and greater wound closure than control (86.59% for SAN versus 50.65% at 22 hours).

Conclusion: SAN demonstrated efficacy and safety in the in vitro assays. The results support the use of Mn-enriched SAN in relief of rhinitis symptoms.

Gilbert Glady

European Bio Immune(G)ene Medicine Association, France

Title: Therapeutic use of microRNAs to prevent and control allergic rhinosinusitis
Speaker
Biography:

Gilbert Glady has completed his MD at the age of 27 years from Strasbourg university of medicine and postdoctoral studies from Besançon and Paris-Nord universities of medicine. He got during all these years an expertise in immunology and immunogenetics and developed also interest for alternative medicines. So he becames at 2010 the creator of the BI(G)MED method and director of EBMA, the European association for training the medical profession at the BI(G)MED. He has participated in numerous international congresses in the field of immuno-allergology, infectiology and oncology with posters and oral presentations.

Abstract:

Inflammatory upper airway diseases, particularly chronic rhinosinusitis (CRS) and allergic rhinitis (AR), have a high worldwide prevalence. CRS and AR involve sustained and exaggerated inflammation that is associated with marked changes in gene and protein expression under tight regulation. MicroRNAs represent one of the fundamental epigenetic regulatory mechanisms used by cells that can mediate posttranscriptional gene silencing of target genes. As fine tuning regulators of gene expression, miRNAs are involved in diverse biologic processes, including cell proliferation, apoptosis, and differentiation, organ development, metabolism, stress responses, and signal transduction. Emerging evidence implicates an involvement of miRNAs in shaping the inflammation pattern in upper airways. Studies regarding the roles of miRNAs in allergic diseases have multiplied during the last 4 years, and the functions of miRNAs in the regulation and pathogenesis of these diseases are more and more better characterized. Recently, miRNAs have been shown to be detectable in cell-free body fluids such as serum and plasma samples. The circulating miRNAs are protected from blood RNAses either by existing in cell membrane-derived vesicles such as exosomes or by forming a complex with lipid-protein carriers such as high-density lipoprotein. So it becomes possible to use such kind of molecules for a therapeutic purpose, and that is what achieve the Bio Immun(G)en Medicine – BI(G)MED – by introducing high diluted microRNAs in nano compounds looking for a fine regulation in different upper airways diseases with an allergic etiology.

Speaker
Biography:

Tasuku Kawano completed his PhD at Tohoku Medical and Pharmaceutical University in 2009. He is presently working as an assistant professor in the Department of Pathophysiology at Tohoku Medical and Pharmaceutical University. He aims to reduce asthma patients. He studies elucidation of asthmatic onset mechanism based on nerve-endocrine-immunity axis. He has been trying for the creation of new fields for the development of novel medicines and preventive drugs in asthma. He has published “The involvement of central nervous system histamine receptors in psychological stress-induced exacerbation of allergic airway inflammation in mice” Allergol Int. 2016 Sep; 65 Suppl:S38-44.

Abstract:

Statement of the Problem: Allergic asthma is characterized by Th2 type inflammation, essentially due to a breakdown of immune tolerance to an environmental allergen. Etiologically, experiences of early-life stress have been demonstrated to be associated with heightened prevalence of adult asthma. However, mechanisms underlying the stress leading to the development of asthma are poorly understood. Therefore, we examine if early-life stress increases the susceptibility to adult-onset asthma through the inhibition of the development of the respiratory tolerance.

Methodology & Theoretical Orientation: Female BALB/c pups were sensitized by intraperitoneal injections of ovalbumin (OVA)/Al(OH)3 on postnatal days (PND) 24 and 29. Respiratory tolerance was induced by the inhalation of OVA on PNDs 18 and 21 before the sensitization. Maternal separation (MS) was used as a model of early-life stress and repeated from PND 17 to 22. On PND 76, the mice were challenged with OVA aerosol. Airway inflammation was evaluated with numbers of inflammatory cells in bronchoalveolar lavage fluid (BALF). The contents of IFN-g, IL-4, IL-5 and IL-13 in BALF were measured by ELISA. The airway hyper-responsiveness (AHR) was assessed by methacholine-induced airflow obstruction.

Conclusion & Significance: In tolerized mice, the numbers of inflammatory cells, the cytokine contents and AHR were remarkably decreased compared with those in non-tolerized mice. However, these effects of the tolerance were significantly reduced by MS exposure. These results suggested that early-life stress exposure has a potential to increase the risk of adult-onset asthma through the inhibition of the development of immune tolerance.

Speaker
Biography:

Heewon Lee is presently persuing her MS-Ph.D integrated course in Pharmaceutical Sciences college of pharmacy, Ewha Woman’s University, Seoul, Korea. Completed B.S. in pharmacy college of pharmacy, Ewha Woman’s University, Seoul, Korea. Awarded with university scholarship & also has a Korean pharmacist license. Research includes studying the function of TCTP/HRF, a multifunctional protein. TCTP/HRF was found in body fluids of allergic patients and its importance was recognized, but the receptor and its mechanism of action were not yet known. Her ultimate goal was to find the HRF receptor, but attempts to isolate and identify it were unsuccessful. In the process, however, she discovered a functional domain that is thought to be the receptor binding domain of HRF. Antibodies targeting this region are being produced and the antibodies with good efficacy will be selected as HRF inhibitors.

Abstract:

We first reported that translationally controlled tumor protein (TCTP) acts as a histamine-releasing factor (HRF) associated with chronic allergic disease when it forms dimers. Despite the lack of signal peptide, HRF was found in nasal lavages, skin blisters and bronchoalveolar lavage fluids in late phases of allergic reaction. In a preliminary study, we found a significant increase in serum HRF levels in patients with asthma and allergic rhinitis. These results have led us to investigate whether HRF can be a therapeutic target for allergic diseases. By screening a phage-displayed 7-mer peptide library, we identified one peptide that showed strong affinity for the dimer TCTP (dTCTP). The peptide named dTCTP-binding peptide 2 (dTBP2) blocked the action of HRF by inhibiting binding to the cell surface. Specifically, dTBP2 inhibited the release of IL-8, an inflammatory cytokine, by inhibiting dTCTP-induced NF-κB and MAPK from human bronchial epithelial cell line BEAS-2B. In addition, dTBP2 dose-dependently reduced the symptom score and eosinophil recruitment to the nasal mucosa in OVA-induced allergic rhinitis mouse model, suggesting that in vivo inflammation-mediated airway pathology was alleviated. In this study, we showed that inhibition of dTCTP could alleviate allergic pathology and showed that dTCTP could be a new drug target for chronic allergic diseases such as allergic rhinitis.

Biography:

Boris Ferko is presetly working at EURRUS Biotech GmbH, Austria

Abstract:

We tested the efficacy of a novel biogenic peptidoamine compound, glutarimide histamine (XC8) in mouse, rat and guinea pig asthma models. Sensitized animals underwent oral treatments for at least 10 consecutive days with titrated doses of XC8 or corticosteroid reference drugs. In mice, XC8 efficiently inhibited eosinophilic lung inflammation of acute asthma disease onset, suppressed mucus hypersecretion, antigen-specific serum IgE or IgG1 titres, and methacholine-induced airway hyperresponsiveness (AHR). In Sephadex-induced migration of eosinophils in a rat model XC8 decreased the content of eosinophils in bronchalveolar lavages (BAL) 2.6-6.4 times. In guinea pig models of asthma and antigen-induced bronchospasm, XC8 reduced the number of degranulated mast cells and basophils in the lung tissue and the degree of degranulation. Moreover, XC8 also reduces hyperactivity of the lungs and reduces mortality of the animals from anaphylactic reactions. Chronic toxicity studies in rats and dogs revealed an excellent safety profile of XC8.

In vitro experiments indicated that the mode of XC8 action might be associated with the suppression of glutaminyl cyclase - an enzyme that converts the immature form of chemokines (CCL2, CCL7, CCL8, CCL13) into the mature form by the reaction of pyroglutamination, thus suppressing the chemokine-driven migration of eosinophils and other cells into the inflammation area and the degranulation of mast cells and basophils.

Our data demonstrate that XC8 efficiently suppresses experimental allergic asthma and provide support for its use as a treatment for human allergic asthma. 

Speaker
Biography:

Luiz Werber-Bandeira is the Head of Clinical and Experimental Immunology Unit - Santa Casa de Misericórdia do Rio de Janeiro, Brazil. He has a degree in Medicine; completed his Post-doctorate in Immuno-Genetics and; PhD in Medicine-Immunology-Dermatology at Federal University of Rio de Janeiro. He is also specialized in Clinical Immunology-Allergy at Federal University of Rio de Janeiro. He is reorganizer of the clinical and experimental immunology unit - Santa Casa da Misericórdia, Rio de Janeiro. 

Abstract:

Background: The gene encoding the adrenergic β2 receptor (ADRβ2) located on chromosome 5q31-32 presents a high allelic diversity characterized by the presence of several single nucleotide polymorphisms (SNPs) associated with different receptor activities at the cellular levels. 45 SNPs have been identified along this gene, some with significant effect on clinical response to β2-agonists. The allelic distribution varies with ethnicity and due to alterations in sensitization and down regulation of these receptors. The existing studies refer to ethnically homogeneous populations, with no data on the distribution of these SNPs in ethnically mixed populations, although certain haplotypes appear to directly affect receptor function.

Objective: The objective of this study was to determine the prevalence of previously described SNPs in the coding region of the ADRβ2 gene, as well as to identify new SNPs in a group of individuals living in Rio de Janeiro through sequencing technique.

Patients & Methods: DNA samples from 162 individuals were subjected to PCR amplification and genotyping by sequencing.

Results: Analysis of the sequences generated identified the presence of nine different SNPs 46 (G>A), 66 (C>T), 79 (C>G), 252 (G>A), 455 (T>G), 470 (T>G), 491 C>T, 523 (C>A) e 579 (C>T) within the sequenced region (899 bp), from which, three: 455 (T>G), 470 (T>G), and 579 (C>T) were not yet described, and the characterization of 14 different haplotypes. The SNPs in codons 27 and 164, two of the most studied, showed different frequencies from those observed in other populations. The SNP in codon 27 was: 8.1% versus 24% in Caucasian-Americans and versus 18.7% in African-Americans. The SNP in codon 164 was: 4.6% versus 1% in Caucasian-Americans and versus 2% African-Americans. The SNP at codon 16, Arg16Gly, showed similar frequency to the one found in the literature in Caucasians and Chinese ethnicity: 54.9% vs. 39%, and 42% and 51% respectively.

Conclusion: The results of this study, although represent a partial mapping of the coding region of the ADRβ2 gene, demonstrated the diversity of this gene, of great clinical importance. The results represent the first data on the partial mapping of the gene ADRβ2 in an ethnically mixed population.

Speaker
Biography:

Chiaki Masuda is a licensed Pharmacist and pursuing her Doctoral degree at Tohoku Medical and Pharmaceutical University, Japan. She has been working on “Analyzing differences in the pathophysiology of allergic asthma between sexes, focusing on the molecular mechanisms underlying the sex-specific effects of dendritic cells”. Her focus is primarily on translational research such as conducting basic immunological studies using mouse models and applying the results obtained in studies of the etiology of asthma in humans.

Abstract:

Statement of the Problem: Prevalence and severity of asthma symptoms after puberty are higher in women than in men. The numbers of IL-13-producing peripheral blood T cells are significantly higher in female than in male patients of atopic asthma. These T cells accelerate the female-predominated Th2-oriented immune response in asthma. The uptake and processing of inhaled allergens by dendritic cells (DCs) are fundamental for sensitization and subsequent elicitation of allergic airway responses. Observational data have suggested that DCs rapidly accumulate in the lamina propria in patients with allergic asthma after allergen challenge. However, the mechanism of DC involvement in the female-predominant Th2 immune responses in asthma is unclear.

Methodology & Theoretical Orientation: Male and female wild-type (WT) mice were sensitized using two intraperitoneal injections of ovalbumin (OVA) and aluminum hydroxide, followed by exposure to OVA aerosol challenges for 1 h on two occasions 4 h apart or administration of OVA intra-tracheal challenge. Here, we investigated the role of two major subsets of DCs in mice, CD11bhi and CD103+, in the orientation of T cells toward a Th2 phenotype observed predominantly in female patients of asthma.

Results: CD11bhi and CD103DC numbers in bronchial lymph nodes in female mice present a significant increase, measured 16 h after OVA challenge, compared to those in male mice. Additionally, CD103DCs in females expressed higher CD86 levels and had a higher potential of driving antigen uptake and Th2-cell differentiation compared to those in males. In contrast, such differences between the sexes were not observed for CD11bDCs.

Conclusion & Significance: These results suggest that the increased number of DCs and specific properties of CD103+ DCs may be involved in the Th2 immune response observed predominantly in female patients of allergic asthma.

Speaker
Biography:

Tatiana Chioro is a Brazilian Physician with large experience in Cosmetic Dermatology. She is Member of Brazilian Society of Dermatology, American Academy of Dermatology and European Academy of Dermatology and Venereology. She is also an MSc candidate at Hospital do Servidor Público Estadual – IAMSPE – São Paulo – SP – Brazil 

Abstract:

Hyaluronic acid (HA) is biocompatible, easy-to-use, and reversible filler which is broadly-based filler in cosmetic medicine. More and more, non-expert physicians and non-physicians practitioners have been performing fillers in a large number of patients, which notices a high risk of unwanted outcomes, either in efficacy and safety fields. Unwanted results can mean overcorrection and asymmetries, as well as adverse events against these injectable fillers. Although HA-based fillers are defined as temporary materials, they can last up to 12 months or longer. Hyaluronidase is an endogenous enzyme that has a potent activity, which lets it to hydrolyze tissue HA, which is the key element of connective tissue. Given that, commercial hyaluronidase, when injected in areas wherein HA-based filler was placed, destroys HA and gives the possibility to adjust overcorrection and asymmetries. Although hyaluronidase has been used worldwide, only a few allergic reactions have been reported. Most of the described patients showed allergic reactions after peribulbar anesthesia for eye surgery despite the large use of HA fillers in aesthetic medicine. A 29-year-old Brazilian female patient was subjected to a 0.01 mL hyaluronidase injection (Pineda Laboratories, Sao Paulo, Brazil) in order to treat a malar hypercorrection as result of filling with HA. After about 10 minutes, she evolved with discrete erythema and edema at the injection site. A vial of 1 mL intramuscular injection of 5 mg/mL betamethasone dipropionate+2 mg/mL betamethasone disodium phosphate 2 mg/mL (BetaTrinta, Eurofarma, Sao Paulo/SP, Brazil) was immediately administered. After 1 hour, however, the patient presented an intense edema in her left hemiface, which suggested angioedema onset; this adverse event was immediately treated by injecting 4 mL of 500 mg hydrocortisone sodium succinate which helped her to clinically overcome such condition. Though, the patient was discharged to home with 40 mg/day/3 days of micronized prednisolone. A complete clinical improvement was observed in five days. In summary, side effects against hyaluronidase injections are rare in accordance with already published scientific literature; however, it is extremely important for professionals of cosmetic medicine to be an emergency conduct at their office.

Speaker
Biography:

Tomomitsu Miyasaka completed his PhD at Tohoku University, Japan. He is an Assistant Professor at Tohoku Medical and Pharmaceutical University, Japan. His research area is Allergy, and he is interested in determining the mechanism(s) that are responsible for the altered asthma severity by sex or related to psychological stress. 

Abstract:

Statement of the Problem: Bronchial asthma is more severe in females than in males after puberty because of stronger Th2-oriented immune response in females. However, the mechanism of the sex difference in asthmatic immune response remains unclear. CD8+ T cells play an important role in regulating the asthma immune response through their suppressive effect on Th2 polarization within the localized lymph nodes.

Theoretical Orientation: In the present study, we investigated the sex-specific effect of CD8+ T cells on the female-predominant asthmatic immune responses using a mouse model.

Results: The number of eosinophil in bronchoalveolar lavage (BAL) fluid, lung Th2 cytokine levels, and IL-4 production by bronchial lymph node cells were significantly higher in wild-type female compared with male mice, whereas no such sex differences were observed between cd8α-disrupted (CD8KO) male and female mice. The adaptive transfer of wild-type male, but not female, CD8+ T cells reduced the number of inflammatory cells in the recovered BAL fluid of CD8KO male, but not female, recipient mice. Male CD8+ T cells produced higher levels of IFN-γ than female CD8+ T cells. Treatment with anti-IFN-γ antibody completely abrogated the sex difference in the suppressive activity of CD8+ T cells on IL-4 production from CD4+ T cells. However, IFN-γ receptor expression on CD4+ T cells was higher in male mice than in female mice. rIFN-γ treatment increased the proportion of IFN-γ receptor α+ CD4+ T cells in male naïve CD4+ T cells more than in female naïve CD4+ T cells.

Conclusion & Significance: These results suggest that female-dominant asthmatic immune responses are induced by the reduced production of IFN-γ by CD8+ T cells and the lower expression of IFN-γ receptor on CD4+ T cells caused by exposure to IFN-γ in females compared with males.

Biography:

Areum Kim is a PhD student at Jeju National University, Republic of Korea. He has research interest in Immunology and Radiobiology. He completed his BA in Nuclear and Energy Engineering at Jeju national University, South Korea from 2009-2013 and; MS in Interdisciplinary Graduate Program in Advanced Convergence Technology & Science at Jeju National University, Korea from 2013-2016.

Abstract:

Sargassum horneri, a species of brown macro algae, has been reported to have several health promoting effects such as anti-viral, anti-coagulant effect, and anabolic activity on bone metabolism or higher plumbum absorption. In the present study, we investigated the immunomodulatory activity of S. horneri using murine splenocytes and bone marrow cultured mast cells. S. horneri was enzymatically hydrolyzed using the celluclast (SHC). Polyphenol-rich fractions from S. horneri (SHP) were also used for assessing the anti-allergic activity in BMCMC. SHC induced the proliferation of splenocytes without cytotoxicity. Treatment with SHC led to a significant increase in the population of CD8+ T cells, CD8+CD25+ regulatory T cells, and granulocytes. SHC also increased the secretion of IFN-γ. Meanwhile, SHP didn’t show any cytotoxicity in BMCMC but significantly decreased the release of β-hexosaminidase in stimulated BMCMC. SHP also decreased the mRNA expression of IL-4, IL-6, IL-13, and TSLP in BMCMC. These findings indicate that S. horneri might modulate the Th2-type immune responses in immune-mediated disease. Therefore, S. horneri could be an excellent candidate for an anti-allergic agent.

Biography:

Jinhee Cho is a PhD student at Jeju National University, Republic of Korea. He has research interest in Immunology, especially Th1/Th2 type immune responses. He completed his BA in Veterinary Medicine at Jeju National University, South Korea from 2008-2014 and; MS in Veterinary Medicine at Jeju National University, South Korea from 2014-2016.

Abstract:

CD244 is a member of the signaling lymphocyte activation molecule (SLAM) family and can exhibit either activating or inhibitory effect on the cytotoxic activity of cells, depending on the density of its ligand CD48 and the availability of its adaptor protein SLAM-associated protein SAP. Although the role of CD244 has mainly been studied in virus infection, its role in autoimmune disease has not been well defined. In the present study, we examined the regulation of CD244 expression in experimental autoimmune encephalomyelitis (EAE), an induced model of autoimmune disease, and determined that the role of CD48 expression on T cells was markedly changed during EAE progression. To determine the type of CD244-expressing cells affected during the EAE progression, flow cytometry analysis was performed. In the spleen of naïve mice, most of the CD244-expressing cells were NK1.1+ NK cells although NK cells were not the major population in the spleen compared to T cells. In addition, the number of CD244+ NK cells was significantly decreased in early and peak stages of EAE compared to the naïve control. At the recovery phase, the numbers of CD244+ CD4+ T cells and CD244+ CD8+ T cells were increased relative to naïve levels, respectively, while the number of CD244+ NK cells returned to the naïve level, consistent with other reports which considered CD244 as one of exhaustion markers in various diseases. In addition, high CD48 expression was associated with IL-17a production. The reduction of CD244 expression in NK cells that infiltrated into the CNS appeared more dramatic than that in the periphery. Our results suggest that CD244 expression correlates with NK cell function during EAE progression.

Biography:

Jinhee Cho is a PhD student at Jeju National University, Republic of Korea. He has research interest in Immunology, especially Th1/Th2 type immune responses. He completed his BA in Veterinary Medicine at Jeju National University, South Korea from 2008-2014 and; MS in Veterinary Medicine at Jeju National University, South Korea from 2014-2016.

Abstract:

CD244 is a member of the signaling lymphocyte activation molecule (SLAM) family and can exhibit either activating or inhibitory effect on the cytotoxic activity of cells, depending on the density of its ligand CD48 and the availability of its adaptor protein SLAM-associated protein SAP. Although the role of CD244 has mainly been studied in virus infection, its role in autoimmune disease has not been well defined. In the present study, we examined the regulation of CD244 expression in experimental autoimmune encephalomyelitis (EAE), an induced model of autoimmune disease, and determined that the role of CD48 expression on T cells was markedly changed during EAE progression. To determine the type of CD244-expressing cells affected during the EAE progression, flow cytometry analysis was performed. In the spleen of naïve mice, most of the CD244-expressing cells were NK1.1+ NK cells although NK cells were not the major population in the spleen compared to T cells. In addition, the number of CD244+ NK cells was significantly decreased in early and peak stages of EAE compared to the naïve control. At the recovery phase, the numbers of CD244+ CD4+ T cells and CD244+ CD8+ T cells were increased relative to naïve levels, respectively, while the number of CD244+ NK cells returned to the naïve level, consistent with other reports which considered CD244 as one of exhaustion markers in various diseases. In addition, high CD48 expression was associated with IL-17a production. The reduction of CD244 expression in NK cells that infiltrated into the CNS appeared more dramatic than that in the periphery. Our results suggest that CD244 expression correlates with NK cell function during EAE progression.

Speaker
Biography:

Inhwa Choi is working for Kyung-Hee University Hospital at Gangdong. Her specialties are in the areas of atopic dermatitis (AD) and allergic diseases, such as allergic rhinitis, asthma and allergic contact dermatitis. Her special interests include disorders of the immune system and she has devoted her time and knowledge to helping her patients reinforce and strengthen their resistance to these ailments through Korean medicine.  

Abstract:

Patients with atopic dermatitis (AD) exhibit various symptoms, especially itching. Recently, herbal medicines (HMs) are being used in combination with antihistamines for the treatment of AD in Korea. While oral  ntihistamines can alleviate itching, HMs appear to exert anti inflammatory effects with minimal side effects. However, there is little evidence regarding the effectiveness and safety of using HMs in combination with antihistamines for AD. To observe the effectiveness and safety of combination treatment with HMs and antihistamines, we performed a retrospective chart review of inpatients with AD who received this combination treatment for at least 7 days in a hospital. Of 163 inpatients, 40 met the inclusion criteria. All patients received HMs three times, and one or two antihistamines, a day after HM intake. A large proportion of patients received first-generation antihistamines. HMs comprised a mixture of an average of 20.69 different herbs in decoction. The mean total, objective, and subjective SCORing Atopic Dermatitis scores showed a significant decrease after combination treatment. Changes in the mean levels of aspartate transaminase, alanine transaminase, blood urea nitrogen, and creatinine were not statistically significant among treatments. There were no adverse events of pseudoaldosteronism or interstitial pneumonia. We observed that the short-term use of HMs in combination with oral antihistamines was safe and effective, with a low risk of adverse reactions. This study was limited by its retrospective design, and prospective studies with long-term follow-up periods are warranted to further elucidate the safety of this combination treatment for AD.