Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 6th International Conference and Expo on Immunology Chicago,IL, USA.

Day 2 :

Keynote Forum

Deepak Shukla

University of Illinois at Chicago, USA

Keynote: Autophagy regulation and herpes simplex virus infection

Time : 09:00-09:35

Conference Series World Immunology Summit-2016 International Conference Keynote Speaker Deepak Shukla photo
Biography:

Deepak Shukla has received his PhD in Microbiology and Immunology from the University of Illinois at Chicago (UIC) during 1990-1996. Currently, he is working as the Marion Schenk Esq. Professor of Ocular Virology in the Departments of Ophthalmology & Visual Sciences and Microbiology & Immunology at UIC College of Medicine in Chicago, IL. He is also the Director of Ocular Virology Laboratory at UIC. He serves on the Editorial Boards of prestigious journals, has been a regular Reviewer for over a dozen reputed scientific journals and has authored over 50 peer-reviewed papers including publications in top rated journals such as Cell, Journal of Clinical Investigation, Journal of Cell Biology, Journal of Biological Chemistry, etc. He has also written two book chapters and holds two international patents for his discoveries. He was the lead discoverer of 3-O sulfated heparan sulfate as the host cell membrane receptor for herpes simplex virus. He has received outstanding research awards from many organizations including American Herpes Foundation, Research to Prevent Blindness Inc.

 

Abstract:

Herpes simplex virus-1 (HSV-1) is a double-stranded DNA virus that causes life-long infections. HSV-1 infections may lead to herpetic stromal keratitis that may advance to corneal blindness. Similarly, genital infections by HSV-2 can result in painful sores and blisters. HSV-1/-2 infections can also cause fatal conditions, such as herpes encephalitis, meningitis or neonatal disease. A major defense mechanism of HSV infection is the control of autophagy, an innate immune defense strategy that would normally degrade the HSV virions. Here, to understand how autophagy controls HSV infection, we tested the effects of various autophagy inducers and inhibitors (physiological and pharmacological) on autophagy modulation in key HSV target cells and progression of infection. While a basal level of virus-controlled autophagy is needed for optimal infection, autophagy stimulation or suppression was confirmed to significantly inhibit HSV infection in various cell types without affecting cell viability. Similar findings were made using HSV corneal infection in mouse models. Our findings are of high significance especially since the cornea is an immune privileged tissue and intrinsic mediators of immunity are the key to controlling the infection. This study establishes the importance of autophagy for regulating HSV infection and provides a proof-of-principle evidence for a novel antiviral control mechanism.

  • Symposium
Location: Berlin
Speaker

Chair

Ahmed G Hegazi

National Research Center, Egypt

Session Introduction

Ahmed G Hegazi

National Research Center Egypt

Title: Cytokines in localized plaque psoriasis treated with by some bee products

Time : 09:35-10:05

Biography:

Ahmed G Hegazi is currently a Professor of Microbiology and Immunology in the National Research Center, Egypt. He has received his Master’s degree in 1979 and his PhD in 1981. He has been the Principal Investigator on multiple research projects within the National Research Center. He has published 211 scientific papers and articles in national and international journals. He has served on the board of multiple national and international scientific journals. He is also the President of the Egyptian Environmental Society for Uses and Production of Bee Products, Secretary of the Egyptian Society of Apitherapy, Secretary General of the African Federation of Apiculture Associations and a Member of the International Apitherapy Commission (APIMONDIA). He has received several awards which include First Class Decoration of Excellence (1995), The Senior Scientist Prize of National Research Center, (1996), The National Scientific Prize In Biological Sciences (1990), The Scientific Prize of The National Research Center (1989), 2 Bronze Medals from The International Innovation Fair of the Middle East, Kuwait (2007), awarded Ghazi Wad Allah Salon Prize (2008) and has 4 patents to his credit.

Abstract:

Background: Several therapeutic modalities have been used for treatment of psoriasis. Apitherapy entails the medical use of bee products as honey, bee venom and propolis.

Objectives: To evaluate bee venom honey and propolis, as a new therapeutic modality for localized plaque psoriasis.

Materials & Methods: Eighty patients were randomized into four treatment groups: Group-I: Received intradermal bee venom twice weekly, Group-II: Received topical propolis and honey ointment in Vaseline base, Group-III: Received oral propolis capsules 3 gm/day and group-IV: Received intradermal bee venom, oral and topical honey and propolis, Group-V: Received drugs. Response to treatment was assessed by calculating PASI score and measuring serum interleukins: IFN-γ, interleukin (IL) 1β, IL-4, IL-6, IL-10, tumor necrosis factor alpha (TNFα) was detected before and after 3 months of treatment.

Results: A significant reduction in both PASI score and serum level of IL-1β and IL 6 was observed in all groups. Changes in PASI score, IFN-γ, interleukin (IL) 1β, IL-4, IL-6, IL-10, tumor necrosis factor alpha (TNFα) were significantly reduced in groups I, IV and V compared to groups II and III. All treatments were tolerable with minimal adverse effects.

Conclusions: Intradermal bee venom and oral propolis are safe and effective treatments of localized plaque psoriasis with minimal tolerable side effects intradermal bee venom has superior results than oral or topical honey with propolis when used alone or in combination with propolis.

 

Biography:

Abstract:

This study was conducted to investigate the influence of propolis on immunological responses with special reference to cytokine level of infected with Toxoplasma gundi and treated with and then the inoculation with 0.1 ml propolis everyday till the end of the experiment (28 days). Immune response of rats was evaluated weekly. Cytokines were detected. The results revealed that the growth promoting effect propolis extract. It was clear that the propolis treated group showed the highest lymphoid organ weight all over the experimental period. Propolis was the highest in the Toxoplasma antibodies titer when comparing with control group from the 2nd week to the end of experiment. Serum levels of cytokines were consistently higher in the treated and propolis infected rats compared with controls. Serum levels of IFN-γ, IL-1 and IL-6, were elevated only at day 7 post-infection.

Break: Networking & Refreshments Break 10:35-10:55 @ Foyer

Mahmoud El Feel

Agriculture Research Center, Egypt

Title: Influence of bee venom as immunostimulant activity

Time : 10:55-11:25

Biography:

Mahmoud El Feel is currently working as an Assistant Researcher, Beekeeping Department, Plant Protection Research Institute, Agriculture Research Center, Ministry of Agriculture, Egypt. He has completed his Philosophy of Doctorate and Master of Sciences in Agriculture, Apiculture, Entomology (Plant Protection) from Cairo University, higher study Diploma in Agriculture (Apiculture & Silk culture) from El Menofea University in 2001 and Bachelor of Science in Agriculture, General Plant Production from Alexandria University in 1998.

Abstract:

The objective of this review was to determine the influence of bee venom (BV) as immunostimulant activity and the immunomodulatory activity of BV on cytokines production. Bee venom acts upon both innate and adaptive immune response. Compounds in bee venom decrease proinflammatory cytokine synthesis (IL-2, IL-12 and IL-4), inactivate both the classical and alternative complement pathway and decrease superoxide anion production in neutrophils. It could be concluded that time and dose-dependent response as well as the type of treated cell line could determine the immunosuppressive and/or immunostimulant property of bee venom that could be effective in future therapeutic strategies.

Biography:

Abstract:

This study conducted to investigate the immunological responses of rats infected with Toxoplasma gundi and treated with 15% Capparis spinosa honey (Saudi Arabia) supplemented orally for a period of 35 days. Immune response of rats was evaluated weekly. Cytokines were detected in honey supplement either in non-infected or infected. Mortality and morbidity rate were assayed where the lymphoid organs weight were determined. The results revealed that oral administration of honey as a natural feed additive through the experiment reduced mortality rates, increase in body weight, lymphoid organ weight. Also antibody titer was raised. Serum levels of cytokines were consistently higher in the infected and honey supplemented rats compared with controls. Serum levels of IFN-γ, IL-1 and IL-6 were elevated only at day 14 post- infection.

Biography:

Mona Mostafa Farid Ganem has completed her MB BCh in 2003 from Faculty of Medicine, Cairo University, Master’s degree in Neuropsychiatry from Cairo University in 2009 and Doctorate degree in Neurology also from Cairo University in 2015. She has worked as a Resident in Neurology Departments of Kasr El Eini Hospitals from 2005-2006, new Kaser Al Ainy Hospital Cairo University from 2007-2009, Dar AL Fouad Hospital from 2008-2012. She was an Assistant Researcher of Neurology from 2009-2015 and Researcher of Neurology at National Research Center since 2015, Neurology Consultant at Mostafa Mahmoud Hospital and Outpatient Clinic since 2012 to till date and was also a Neurology Consultant at Asseer Central Hospital Saudi Arabia in 2015 & 2016.

Abstract:

Parkinson's disease (PD) is a neurodegenerative and neuro-inflammatory disorder of the central nervous system, it has been known as movement disorder, also it is becoming recognized that for its non-motor characteristics that includes cognitive difficulties. Cognitive function is broadly defined as an intellectual pro­cess by which one becomes aware, perceives or compre­hends ideas. It involves all aspects of perception, thinking, rea­soning and remembering. Cognitive impairment means a deterioration of the mental processes such as memory, decision, understanding and reasoning. Cognitive impairment may be associated with behavioral disorders. There are different cognitive domains that accompany Parkinson's disease, the most common affected domains include: Executive functions, attention, learning and memory. Many studies reported that Bee venom therapy has anti-inflammatory and anti-neurodegenerative effects that improve PD symptoms. Also it attenuates the activation of the microglial response, reduces expression of the inflammation markers and reducing glutamatergic cell toxicity. Also it was reported that Bee venom therapy plays an important role in improving cognitive functions through blocking small conductance calcium-activated potassium channels (SK channels), also can increase brain-derived neurotrophic factor (BDNF).

  • Autoimmune Diseases
    Viral Immunology: Emerging and Re-emerging Diseases
    Immunotherapy & Cancer Immunotherapy: From Basic Biology to Translational Research
    Immunology and Diabetes
    Vaccines and Immunotherapy
    Allergy and Asthma
    Mucosal immunology
Location: Berlin
Speaker

Chair

Charles J Malemud

Case Western Reserve University School of Medicine, USA

Speaker

Co-Chair

Deepak Shukla

University of Illinois at Chicago, USA

Session Introduction

Hana Zelenkova

DOST Svidnik, Slovakia

Title: Therapeutic management of extensive pressure ulcer affecting occipital and parietal bone

Time : 12:25-12:55

Biography:

Hana Zelenkova has been active in Dermatovenerology since 1973. Since 2000 she has been directing her own Private Clinic of Dermatovenereology. She has given more than 650 expert lectures in Slovak Republic as well as abroad and has 420 scientific publications. She is the Founder and President of the Slovak Society for Aesthetic and Cosmetic Dermatology President of the traditional international DERMAPARTY congress.

Abstract:

A female patient of 81 years, in good health condition, living on her own in a house suffered a stroke in 2001 and in 2010 she was diagnosed with an inoperable brain tumor (meningioma). Apart from occasional memory loss and short term nausea she had no difficulties and could take care of herself. Following a visit she paid to her relatives in December 2013 she suddenly lost consciousness, fell and was left lying on a stone floor until her relatives found her after two days. She developed an extensive pressure ulcer in the location between her shoulder blades and the occipital and parietal bone in the skull, accompanied by loss of hair, skin and subcutaneous tissue up to the bone in the area of 10×12 cm. After two months of hospitalization at the Department of Neurology, her general condition has been stabilized, she communicates, but her mobility is limited. The pressure ulcer between her shoulder blades heals quite effectively, the manifestations on the cranium are stagnant, the pressure ulcer shows callous margins and the bone is colored dark brown to black. Since March 2014 the therapy included gel preparations and we also have commenced stem cell therapy with a very good effect in October 2015; an extensive pressure ulcer is completed healing.

Break: Networking & Lunch Break 12:55-13:45 @ Athens

Deepak Shukla

University of Illinois at Chicago, USA

Title: Development of a novel virus-trapping vaccine platform against genital herpes

Time : 13:45-14:15

Biography:

Deepak Shukla has received his PhD in Microbiology and Immunology from the University of Illinois at Chicago (UIC) during 1990-1996. Currently, he is working as the Marion Schenk Esq. Professor of Ocular Virology in the Departments of Ophthalmology & Visual Sciences and Microbiology & Immunology at UIC College of Medicine in Chicago, IL. He is also the Director of Ocular Virology Laboratory at UIC. He serves on the Editorial Boards of prestigious journals, has been a regular Reviewer for over a dozen reputed scientific journals and has authored over 50 peer-reviewed papers including publications in top rated journals such as Cell, Journal of Clinical Investigation, Journal of Cell Biology, Journal of Biological Chemistry, etc. He has also written two book chapters and holds two international patents for his discoveries. He was the lead discoverer of 3-O sulfated heparan sulfate as the host cell membrane receptor for herpes simplex virus. He has received outstanding research awards from many organizations including American Herpes Foundation, Research to Prevent Blindness Inc.

Abstract:

Efforts to generate an effective immuno-protective agent against recurrent genital infections caused by herpes simplex virus-2 (HSV-2) have seen only limited success. The virus can be transmitted sexually as well as from mothers to neonates. It is also a key facilitator of HIV co-acquisition. No vaccine or protective immunotherapy exists to control the viral transmission or dissemination. Here, we describe a nanoimmunotherapy approach using our uniquely designed zinc oxide tetrapod nanoparticles (ZOTEN). ZOTEN carry engineered oxygen vacancies, which allows HSV-2 to bind the nanoparticles with high affinity. As a result, ZOTEN can be used intravaginally as a microbicide that blocks HSV-2 genital infection in female BALB/c mice. The strong HSV-2 trapping ability of ZOTEN reduced local virus production, clinical symptoms of infection and effectively decreased the animal mortality rate. While preventing HSV-2 infection by virus trapping, the virus-bound ZOTEN promoted the presentation HSV-2 virions to mucosal antigen presenting cells. We demonstrate that dendritic cells can capture and process the bound virions for antigen presentation. Due to efficient processing of ZOTEN-bound virions a clear enhancement of cell and antibody-mediated responses was observed. Our results demonstrate that ZOTEN treatment can suppress not only a primary but also a re-infection by HSV-2. To conclude, we provide evidence for the protective efficacy of a virus-trapping vaccine platform against genital herpes infections.

Biography:

Vaibhav Tiwari  received his PhD in Biotechnology from the Banaras Hindu University (India). Currently, he is working as the Associate Professor in the Departments of Microbiology & Immunology at Midwestern University, IL. His area of interest include understanding molecular mechanism of herpes virus entry and associated inflammation. His previous work includes cloning and characterization of 3-OST isoforms for HSV entry and spread, discovery of novel phagocytic uptake and generation of anti-HS/3-OS HS peptides against HSV entry. He has authored over 50 peer-reviewed papers in peer reviewed journals (Journal of Cell Biology, Journal of Biological Chemistry, and Journal of Virology).

Abstract:

Ocular herpes simplex virus (HSV) infection of the eye is the most frequent infectious cause of vision impairment in the industrialized world. Using a cytokine antibody array we assessed inflammatory markers induced as a result of HSV-1 infection in human iris stromal (HIS) cells. We used HSV-1 (KOS) 804 syncytial virus strain at a low (0.01) multiplicity of infection (MOI) to infect HIS cells to monitor inflammatory response. Our data indicated that there was a greater signal intensity of MCP-2, TIMP-2, IL-6, and IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), I-309, intercellular adhesion molecule 1 (ICAM-1), IL-6 soluble receptor (IL-6sR), interferon-inducible protein 10 (IP-10), macrophage inflammatory protein 1β (MIP-1β) and soluble tumor necrosis factor receptor 1 (sTNFR1) compared to mock infected cells. A release of multiple pro-inflammatory cytokines may have greater implications in terms of HSV-1-mediated pathology. For instance, the up-regulation of IL-6 have suggested stimulating the secretion of vascular endothelial growth factor (VEGF) in the cornea, implicating possible roles for initiating neovascularization by HSV-1 infection of HIS cells as well. Our results provide evidence for the first time that HIS cells are susceptible to HSV-1 entry/spread and verify the essential viral and host receptors involved, thus establishing an in vitro model to study iris stromal infection and the intrinsic mediators of inflammation. The fact that many of the inflammatory mediators are seen in the absence of the host immune response suggests a great importance for a usage of an in vitro HIS cell model. Future studies using this model may further help distinguish between the contributions from infected cells and those from the infiltrating immune cells during HSV-1 infection. This model may also serve as a platform to test for potential therapeutics that may help against HSV-1-induced iritis. For instance, G2, a peptide isolated against the receptor 3-OS HS, has previously been shown to decrease HSV-1-induced mouse corneal infection. With this in vitro model, we may be able to assess how inhibiting various stages of viral attachment and entry may affect the chemokine induction. Along the same line, this model will also be a new and an easy step to screen for effective drugs that reduce inflammatory conditions in context with HSV-1 infection of the iris stroma.

Biography:

The author (researcher) of the current report, Dr Simon Raymond MPH, is a consultant (specialising in medical and scientific research) and an Alumni of Melbourne University (Rank of Number 1 in Australia and Number 33 in the World). The above stated researcher has acted as a reviewer for the respected Medical Journal of Australia, has received invitations internationally to review from prestigious medical journals including JAMA (Journal of American Medical Association) Network, received award in recognition of his research by Royal Australasian College of Surgeons (PSC, 2006) and invited to conferences internationally as an official delegate and researcher, including that in USA and China. Dr Simon Raymond has acted as the principle researcher in the highest powered form of medical trial—Randomised Controlled Trial (RCT). The above stated researcher is also a member of the Golden Key International Society for honoured and outstanding academics and has been cited as a notable global leader.

Abstract:

This report identifies significant issues: A) The lack of successful antiviral drugs (therapies) despite many years of pursuit; B) No cure for HIV despite many years of exploration. The pathways to combat HIV and other viruses to date: 1) virus replication; 2) enhancement of immune function. Given the lack of success achieved by these two pathways, it would seem reasonable to direct focus at development of a new strategic pathway. This report presents the development of the new strategic pathway for antiviral therapies represented by “site attachment inhibition (or, negation of cellular attachment by viruses).”  Further to this, HIV is used in case analysis with strategic measures detailed including prenatal genetic therapy focusing on mutagenesis and knock out, targeted at genes (receptors; and, surface proteins) including CCR5 and CXCR4, as a means of achieving innate resistance (immunity) similar to the commonly known CCR5-Δ32 mutation, in addition to treatment strategy following established infection designed to block attachment of the virus to CCR5 and CXCR4, including blockade of the receptors (analogous to beta blockade), stem cell therapy, radiation, and targeted therapy designed to attack the mechanisms of the virus in its attachment ability to the given receptors (CCR5, CXCR4) and any other relevant. Support for site attachment inhibition strategy was further consolidated through consideration with respect to advanced information technology in which one key mechanism for virus removal is represented by negation of site attachment. Other strategies and the concept of low-level virus consciousness are presented, in addition to reinforcing new understanding contributed to current medical knowledge. 

Subsequent research by the author of this report has also conceptualised site attachment inhibition for other infective agents including bacteria. 

In conclusion, this research presents the development of the new strategic pathway for combatting infective agents represented by site attachment inhibition (or, negation of cellular attachment by infective agents). This is particularly important in the current context of antibiotic resistance and deficiencies in effective antiviral drugs (therapies).

Biography:

Ambreen Gul Muazzam has obtained the Certificate in Life Science Enterprise (LSE) from University of Toronto, School of Continuing studies, Mississauga campus, Ontario, Canada. She has joined the Institute of Biomedical and Genetic Engineering (IB&GE) in 2003 as Scientific Officer after receiving her Master’s degree in Biochemistry and Molecular Biology from Quaid-i-Azam University, Pakistan. She was then promoted to the post of Senior Scientist in the year 2008. Concurrently, she has completed her MPhil from Quaid-i-Azam University, Islamabad, Pakistan. She has published papers in international journals. Her research interests include population and disease genetics. Her particular research focus is on diagnostics and molecular studies of hepatitis B and C as it is one of the major health problems that Pakistan is facing. She is also involved in cell culturing and cytotoxicity of nanoparticles and organic compounds against human cancerous cell lines. She has also experience working in the Quality Control Department of Pharmaceutical Company as a Microbiologist.
 

Abstract:

Introduction & Aim: Rheumatoid arthritis is an autoimmune disease with poorly understood pathophysiology. Genetic components of disease etiology, especially human leukocyte antigen (HLA) associations are well known. Ethnic differences account for a number of variations in disease association with the HLA locus and there seem to be differences in various studies regarding its genetic predisposition. This study was aimed at determining the contribution of DRB1 and DQB1 components of HLA class II in rheumatoid arthritis in a Pakistani cohort.

Method: For this study, 110 patients and 120 healthy controls from the same geographical area and matched ethnicity were enrolled. Blood DNA was isolated from all the subjects and HLA alleles were typed following allele specific amplification. Subsequently, haplotypes were generated and allelic and haplotype distribution frequencies were compared among the patients and controls using χand Arlequin software. The data obtained by this analysis were also compared with other reported associations found in the Pakistani population by meta-analysis.

Results: HLA allelic status was determined among the patients and controls from the same geographical area to account for differences in ethnicity and environmental factors. Significant associations were found for alleles as well as haplotypes among the patients of rheumatoid arthritis. DRB1*10, DQB1*05 and DQB1*602 were found to be associated with disease susceptibility, whereas DRB1*11 and DQB1*02 had protective effect against the disease. Similarly, haplotype DRB1*10-DQB1*05 was associated disease risk, whereas DRB1*07-DQB1*02 and DRB1*11-DQB1*0301 had a protective effect.

Conclusion: There is a significant DRB1 and DQB1 allele and haplotype association with rheumatoid arthritis susceptibility and protection.

Break: Networking & Refreshments Break 15:45-16:05 @ Athens
Biography:

Arunabha Ray is the Director-Professor and Chair of the Department of Pharmacology at the Vallabhbhai Patel Chest Institute and Faculty of Medicine, University of Delhi, India. He has more than 37 years teaching and research experience in basic and clinical pharmacology and toxicology with specialization in Immunopharmacology. He has been the recipient of several awards and honors for research excellence. He has more than 150 research publications, author of several text and reference book chapters, Editor of 04 books in his areas of expertise and author of a textbook in pharmacology.

Abstract:

Allergic disorders result from dysregulation of the immune system and immunomodulatory and related anti-inflammatory agents from the cornerstones of pharmacotherapy. Bronchial asthma is a heterogeneous disease primarily of allergic origin, involving inflammation of the airways accompanied by airway hyperactivity and reversible bronchoconstriction. Airway inflammation is central to asthma and complex process involving the interactions between cellular and humoral components. Immunological mediators produced by inflammatory cells such as mast cells, eosinophils, basophils, neutrophils, dendritic cells and lymphocytes play crucial roles in asthma pathophysiology. The current approach to the management of asthma includes conventional drug therapy with corticosteroids and bronchodilators. However these drugs, in addition to being expensive, produce various local and systemic adverse effects which restrict their use. This has lead to search for safer and more viable alternative forms of therapy from the traditional system of medicine. Traditional systems of medicine (Unani and Ayurveda) are rapidly emerging as viable alternative treatment strategies for many chronic diseases and effectively use medicinal plant derived products for therapeutic benefits with wider margins of safety. Herbal drugs obtained from medicinal plants are used singly (monoherbal) or in combination (polyherbal) and have great potential as viable alternatives/adjuncts for allergic and immunological disorders. Modern scientific methods are being increasingly adopted to validate the effects of such agents used in the traditional systems of medicine. Translational research in medicine is a two-way street and aims at breaking down barriers between clinical and basic medical sciences to promote rapid transfer of knowledge from bench to bedside and vice versa. In pharmacological sciences and drug development, this concept is being utilized for accelerating the conversion of basic and/or clinical research findings to sustainable health care solutions. UNIM-352 is a polyherbal formulation, used in traditional Unani medicine for bronchial asthma and clinical and experimental studies were conducted to validate their observed effects. In the clinical study, UNIM-352 significantly enhanced the therapeutic effect of standard anti-asthma therapy as assessed lung function tests and symptomatology, as compared to the placebo group, indicating its efficacy as an adjunct therapy. It also reduced the incidences of adverse effects seen after conventional therapy. In the experimental study, UNIM-352 demonstrated differential degrees of anti-inflammatory, immunomodulatory and antioxidant effects in rats, by using well established biomarkers. The results indicate that this polyherbal agent, by virtue of its immunomodulatory and anti-inflammatory effects, could be used as an alternative/adjunct in the treatment of bronchial asthma. This study further highlights the importance of a translational approach in traditional systems of medicine and herbal drug research which could rationalize drug therapy of allergic/immunological disorders.

Biography:

Km Neelofar is currently a PhD student in Rajiv Gandhi Centre for Diabetes and Endocrinology, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, India. Presently she is also a Senior Research Fellow (SRF), Indian Council of Medical Research, India. Her research work is on chronic kidney disease in diabetic patients included biochemical, molecular and immunological aspects related for the same.

Abstract:

Non-enzymatic reaction between proteins and glucose leads to glycated proteins which, depending on the number of glucose molecules attached to them. Numerous studies in vivo have reported strong involvement of glycated-HSA in the development and progression of chronic complications of diabetes mellitus. In this study, HSA was purified from diabetic patients with and without chronic kidney disease (CKD) and healthy subjects and immunological studies have been done to detect the presence of autoantibodies against glycated-HSA in diabetic patients. Antioxidant activity of isolated glycated-HSA was also evaluated by RBCs hemolysis test. Result indicates that free radical scavenging capacities of HSA were decreased in diabetic patients with or without CKD. Furthermore, ELISA results showed presence to autoantibodies towards glycated-HSA in diabetic patients. Strong binding and inhibition of anti-Amadori-albumin-IgG by HSA purified from diabetic patients with or without CKD was found significantly high, while very low inhibition was observed by HSA purified from healthy subjects. These results point towards epitope sharing between the Amadori-albumin and the HSA isolated from diabetic patients. Thus we can conclude here that glycation-induced modifications have a determinant impact on functional properties of HSA that may be related to alteration in its conformation. Because of this deformity, oxidative state may have increased in diabetic patients especially with CKD and glycated albumin could not provide its specific duty towards biological system. This glycated-HSA may be recognized as foreign molecule by immunological system and autoantibodies have been generated against them that may play significant role in disease progression. Findings of this study indicate pathogenic role of glycated-HSA in initiation and acceleration of kidney dysfunction in diabetic patients with CKD.

Leonora Hana-Lleshi

Allergology & Immunology, Regional Hospital, Gjakova, Kosovo

Title: The role of postive influence of venom immunotherapy (VIT) on other allergies

Time : 17:05-17:35

Biography:

Abstract:

Introduction: Venom immunotherapy (VIT) is the definitive treatment of Hymenoptera venom allergies.

Hymenoptera venom allergy is an immunoglobulin E (IgE)- mediated hypersensitivity to the venom of the insect order Hymenoptera.

This allergic reaction may be caused by stings from a number of species in this insect order, occurring only in persons who have previously been sensitized to Hymenoptera venom.

Signs and Symptoms: Most Hymenoptera stings cause small local reactions of no significant medical consequence, these usually peak in intensity at 48 to 72 hours. 

Large local sting reactions typically resolve gradually over 5 to 10 days

Systemic reactions cause signs and symptoms in one or more organ systems and are almost always IgE-mediated. 
Systemic reactions usually cause signs and symptoms starting within minutes following a sting. In general, the sooner the symptoms occur, the more severe the reaction is. 

Pathophysiology: Both systemic and large local reactions to stinging insects are usually caused by IgE-mediated reactions to Hymenoptera venom. At least one prior sting is required to sensitize a person to venom, and sensitization is more likely to occur following multiple simultaneous stings or subsequent stings occurring over a relatively short period of time.  Once sensitization has occurred, a sting can cause mast cell and basophil degranulation, resulting in release of the histamine and other inflammatory mediators responsible for the signs and symptoms of anaphylactic and some large local reactions.

  Allergic reactions to bee venom can be severe enough to cause anaphylactic shock, which can be fatal.
 

Allergy Efficacy of VIT (Venom immunotherapy): VIT is extremely efficacious in preventing subsequent systemic reactions in patients with stinging insect allergy. Efficacy is highest with mixed vespid venom; it is 98% effective in preventing subsequent systemic reactions with a maintenance dose of 300 μg (100 μg per venom )

During the period of two years of VIT of my observed patients, I verified that the subjects 12 years old; gender: female and 26 years old gender male was allergic in: pollens and bee venom with anaphylactic allergic reaction.  Specific Ig- E was detected with POLYCHECK (Bio-Check). Until now I’m performing by schematic regimen SCIT in the upper external side of arm and every time the patient is under my observation for 30 minutes After one year of VIT with Anallergo vaccine, my patients has repeated Specific Ig-E on pollens and hymenoptera venoms, with the parameters of to first patient:
   
Bee venom has fallen  from 5-4;Alder pollen: 1-0;Birch pollen : 2-0; Hazelnut pollen: 2-1;Beech pollen: 2-0;Oak pollen: 2-1;Pine: 2-0;Rhizopus nigrans:2-0;Grass mix: 3-1 and house dust from 2-0.
Second patient A.V. 25 yrs old, gender M allergic on pollens and bee venom after one year of VIT with Anallergo vaccine the parameters of bee venom has fallen down:6-3;beech pollen :1-0;house dust mites:1-0;grasses mix: 2-2 has remained the same.

Matherial and Methods: L-Tyrosine-adsorbed subcutaneous immunotherapy (SCIT) for hymenoptera venom ANALLERGO (Apis mellifera) L-tyrosine delayed immunotherapy consists of two initial vials and one maintenance vial. The role of L-tyrosine is to slow down allergen bioavailabilty.

Conclusion: So I need to follow 3 -5 years (the duration of immunotherapy) the patients analysis for definitive conclusion about the efficiency of VIT and its correlation of positive influence to pollen allergy? But not only VIT on this down below example of one difficult case report and mastocytosis can be evaluated and the combination of anti Ig-E treatment with Omalizumab can be combined.
 It's raported that 2-5 % of subjects can present false negative results in"vivo"and in "vitro" testings such a:SPT;IDR testings; specific Ig-E detections. It's recomended to perform testings minimum after 4 weeks after a stung,if negative after 2,6 months if still are negative always to think about mastocytosis and  occult mast cell release  performing serum tryptase levels,BAA with flow cytometry to detect CD63+ and CD203c+ which are markers of basophil activation because is evaluated one case report with fatal consequesies on MedScape.

Biography:

Abstract:

Anti-Programmed Death 1 (PD-1) blockade therapy aims to restore antitumor immunity by impeding interactions of PD-1 receptors on tumor-reactive T cells with PD-1 ligands (e.g., PD-L1/B7-H1) expressed by tumor cells. Clinical trials with PD-1 and PD-L1 blockade have demonstrated promising therapeutic responses in 17-40% of patients with advanced malignancies. However, clinical outcomes are variable with some patients achieving rapid and durable complete responses to both primary anti-PD1 therapy or upon re-induction, others experiencing early pseudo-progression followed by significant reduction in tumor burden with continued therapy, while a subset of patients will show no clinical benefit. It is still unclear what ultimately separates responders from non-responders and there are no criteria by which to identify patients who might derive late clinical benefit. We propose an individualized strategy of identifying patients most likely to benefit from anti-PD1 therapy based on the sensitivity of their PD-1+ CD8+ cytotoxic T lymphocytes (CTLs) to anti-PD-1 blockade. We propose that this sensitivity is influenced by the status of PD-1 engagement with its ligand PD-L1 at the tumor site and also systemically, which determines the reversibility of PD-1+ T cells. The release of biologically active soluble sPD-L1 (sB7-H1) into the circulation contributes to global immunosuppression and indirectly affects the efficiency of anti-PD-1 blockade. Since we co-discovered B7-H1 (PD-L1) in 1998 by Dr. Dong, mentor and co-investigator, we have been working on dissecting the mechanism of action of B7-H1 and its receptor PD-1. Recently, we identified that Bim (BCL-2 interacting mediator of cell death) a pro-apoptosis molecule, is a downstream signaling molecule of the PD-1 pathway and that high Bim levels are associated with poor survival in patients with metastatic melanoma. The interaction of PD-1 and PD-L1 leads to Bim up-regulation in human primary CD8+ T cells via AKT activation and Bim phosphorylation. Among tumor-reactive PD-1+ CD11ahigh CD8+ T cells in the peripheral blood of metastatic melanoma patients, Bim expression was significantly associated with expression of PD-1 and effector cell markers. However, higher Bim expression and higher frequency of circulating Bim+ PD-1+ CD8+ T cells were identified in patients who derived clinical benefit from anti-PD-1 therapy compared to patients with radiographic progression at 12 weeks; moreover this cell population decreased significantly after successful anti-PD-1 therapy. Our study reports a crucial role of Bim as a downstream signaling molecule of PD-1, which may be important in both T cell activation and apoptosis and reflects the status of PD-1 interaction with its ligand PD-L1 in tumor reactive effector CD8+ T cells. Measurement of Bim levels (frequency and MFI) in the peripheral blood of patients with cancer may be a less invasive and more sensitive way to monitor or possibly predict responses to anti-PD-1 therapy, although future prospective analyses are mandatory to validate Bim as a biomarker of response in the clinic. Our group has also established the existence of sB7-H1 in sera of patients with cancer (renal cell carcinoma and melanoma) and showed that the protein is biologically active and capable of triggering apoptotic signals in target T-cells due to retention of PD-1 binding domain. Increased sPD-L1 (sB7-H1) levels predictably would lead to increased Bim levels and increased T cell apoptosis. Thus, simultaneously determining serum sPD-L1 levels and Bim in tumor-reactive CD8+ T cells may have more predictive value than either marker alone to predict the response to anti-PD-1 therapy and also identify patients who may benefit from dual immune checkpoint blockade to remove noxious immunosuppressive sB7-H1 molecules.

Biography:

Zarina Arif has completed her PhD in 1993 from Aligarh Muslim University, India. She has worked as a Research Assistant (1993-2008) at the College of Applied Medical Sciences, King Saud University, Riyadh, Kingdom of Saudi Arabia. She has worked as a Research Associate for six months at Department of Biochemistry, Faculty of Medicine, AMU, India. She has also worked as a Postdoctoral Fellow of the University Grants Commission, New Delhi from 2012-2015. She is presently working as an Assistant Professor at J.N. Medical College, Aligarh, India. She has attended several national and international conferences and has published 20 papers in international journals.

Abstract:

It has been suggested that stress can play a major role in the etiopathogenesis of numerous diseases including diabetes mellitus. Superoxide and nitric oxide are two such stressors produced during inflammation in high amount. They can combine to produce peroxynitrite anion (ONOO-) which is potent oxidizing and nitrating agent. Thus, its interaction with biomolecules can cause oxidation as well as nitration. In the present study, albumin was modified by peroxynitrite and structural changes have been studied by UV, fluorescence, CD and Congo red binding. Analysis of modified-albumin showed increased level of carbonyl, nitrotyrosine and dityrosine. Thiol content was significantly reduced in modified-HSA. Reduction of plasma antioxidant power has been reported in diabetes mellitus and under such conditions peroxynitrite may modify albumin. This may modify the antigenic properties of albumin. Subsequent processing of modified-albumin by immune cells may generate autoantibodies. Thus, peroxynitrite-modified-HSA was used as antigen for detecting autoantibodies in diabetes mellitus sera by ELISA. Peroxynitrite-modified-HSA was bound by the diabetic autoantibodies. The study demonstrates that peroxynitration can generate immunologically active epitope on HSA.

Biography:

Sidra Islam is currently pursuing PhD from the Department of Biochemistry, Faculty of Medicine, Aligarh Muslim University, India. She has published 3 papers in international journals and 2 are in communication.

Abstract:

Immunoglobulin G (IgG) is the most abundant immunoglobulin of the total immunoglobulin pool in the serum and has been found susceptible to damage by reactive oxygen species (ROS). This study aims at exploring the alterations in the structural characteristics using various biophysical and biochemical methods. Modified IgG showed hyperchromicity in UV-vis spectroscopy, quenching in tyrosine fluorescence and cross linking in SDS PAGE. Changes in secondary structure were evident by Far UV-CD and FTIR. The modified IgG showed enhanced hydrophobicity, increase in carbonyl and reduction in the sulfydryl content. DLS studies point towards increase in the hydrodynamic radii, while DSC analysis showed enhanced thermodynamic stability of the modified IgG. Hydroxyl radical induced aggregation was confirmed by enhanced ThT specific fluorescence intensity and a red shift in the Congo red specific fluorescence intensity in the modified IgG and by the transmission electron microscopy. The immunogenic potential of native and OH treated IgG was probed in experimental animal. The modified IgG was highly immunogenic inducing high titer antibodies. Furthermore, antibodies against native and OHmodified IgG in RA patients were detected by direct binding and inhibition ELISA. The data showed preferential binding of RA autoantibodies to hydroxylated IgG in comparison to the native counterpart. Thus it can be concluded that structural changes generated neoepitopes on IgG causing enhanced antibody production. Also, OH modified IgG can serve as a novel antigen with a possible role in etiopathogenesis of RA.