Day 1 :
Keynote Forum
Aaron Lerner
AESKU.KIPP Institute, Germany
Keynote: New serological markers for celiac disease diagnosis: anti-neo-epitope human and microbial transglutaminases antibodies
Time : 10:00-10:30
Biography:
Professor Aaron Lerner after receiving his MD from the Sakler school of medicine, Tel-Aviv University (1976), Professor Lerner specialized in Pediatrics ( 1982 ), Pediatric Gastroenterology and Nutrition ( 1984 ) and Adult Gastroenterology ( 1987). Took several senior positions as head of Department of paediatrics (1995-2005) and head of Pediatric Gastroenterology and Nutrition unit, at the Carmel Medical Center, Haifa, Israel. Finished his Medical Management degree M.H.A, at Ben- Gurion University, Beer-Sheba, Israel (1999), spent research sabbaticals in Hahnemann University, Philadelphia, PA, USA (1991), State University of North Carolina, Chapel Hill, N.C,U.S.A (2005) and currently, in an extended scientific sabbatical in Aesku. Kipp Institute, Wendelsheim, Germany.(2014-16).Prof. Lerner presented in numerous international congresses, mainly of pediatrics, nutrition and autoimmunity, published 250 manuscripts in peer reviewed journals and is on the editorial board of 14 international journal.
Abstract:
The guidelines of ESPGHAN for the diagnosis of pediatric celiac disease (PCD) rely on anti-human tissue transglutaminase (tTg) as the prime and unique antibody for screening PCD population. Microbial Tg (mTg)is a family member of human tissue transglutaminase (tTg). Both enzymes,tTg and mTg,complexed to gliadin present neo-epitopes and antibodies against these complexes are called tTgneo-epitope andmTg neo-epitope. mTg is capable of cross-linking numerous molecules. Despite declarations of mTg safety, direct evidence for immunogenicity of the enzyme is lacking. The reliability of those antibodies in CD was evaluated.rnMaterials & Methods: The serological activity of mTg, tTg, mTg neo-epitope and tTg neo-epitope were studied in: 95 pediatric celiac patients (CD), 99 normal children (NC) and 79 normal adults (NA). Sera were tested by ELISAs, detecting IgA, IgG or both IgA and IgG: AESKULISA® tTg (tTg, RUO), AESKULISA® tTg New Generation (tTg neo-epitope (tTg-neo)), AESKULISA® mTg(RUO) and AESKULISA® mTg neo-epitope (mTg-neo, RUO). Marsh criteria were used for the degree of intestinal injury.rnResults: Comparing pediatric CD patients with the 2 normal groups: mTg-neo IgA, IgG and IgA+IgG antibody activities exceed the comparable mTg ones (p<0.0001). All mTg-neo and tTg-neo levels were higher (p<0.001). tTg IgA and IgG+IgA were higher than mTg IgA and IgA+IgG (p<0.0001). The levels of tTg-neo IgA/IgG were higher than tTg IgA/IgG (p<0.0001). The sequential antibody activities reflecting best the increased intestinal damage were: tTg-neo IgG ≥ mTg-neo IgG > mTg-neo IgA+IgG > tTg-neo IgA. Taken together, mTg-neo IgG and tTg-neo IgG correlated best with intestinal pathology (r2=0.989, r2=0.989, p<0.0001, p<0.0001, respectively).rnConclusion: mTg is immunogenic in children with CD and by complexing to gliadin its immunogenicity is enhanced. It represents a new serological marker for CD and matches the performance of the tTg neo-epitope. Both antibodies correlate with intestinal damage to the same degree. The neo-epitope tTg and mTg are new powerful serological markers for CD diagnosis. Further studies are needed to explore the pathogenic potential of those antibodies in CD.rn
Keynote Forum
Jurgen Bernhagen
Ludwig-Maximilians University of Munich, Germany
Keynote: MIF proteins as prototypical innate chemokines in inflammatory and cardiovascular disease
Time : 10:30-11:00
Biography:
Jurgen Bernhagen has studied Biochemistry and Immunology at the University of Tübingen, Germany and at Queen Mary College, London, UK. He has performed a sandwich PhD thesis at the University of Tübingen and at the Picower Institute for Medical Research, Manhasset, NY, USA and trained as a Post doctorate at the Picower. He is currently a full Professor of Biochemistry and Molecular Cell Biology at RWTH Aachen University, Germany, and the Chair and Director of the homonymous institute. His main research interest has been on cytokines, chemokines and their role in inflammation with a focus on MIF and the biochemical and structural features and mechanisms of such inflammatory mediators. He has also studies the COP9 signalosome, disease models encompass rodent model of atherosclerosis, sepsis, liver and kidney disease as well as colitis and colorectal cancer. He has authored more than 120 peer-reviewed papers in these areas, several of them published in leading journals such as Nature, Nature Medicine, or PNAS. He serves on the Editorial Board of several journals and serves on several Review committees for extramural funding and various fellowship organizations.
Abstract:
Inflammatory processes such as those promoting atherosclerotic lesion formations are pivotally driven by components of the innate and adaptive immune axis. Chemokines and their receptors are particularly prominent part of the innate immune arm. While the role of classical chemokines, i.e., belonging to the CC or CXC families is increasingly well understood, an emerging family of chemokine like inflammatory mediators termed ‘innate chemokines’, CLF chemokines or micro-chemokines, which additionally struc¬turally and functionally overlaps with the mediator class of alarmins, has been identified, but it yet has to be comprehensively characterized regarding its molecular mechanism and role in disease. For example, innate chemokines modulate inflammatory reactions in the atherogenic arterial wall and numerous other inflamed tissues, but the precise receptor signaling mechanisms are still only poorly understood. What is known is that many innate chemokines share functional homology with classical chemokines and signal through classical chemokine receptors, whereas they do not exhibit conserved structural features such as N-terminal tandem cysteine residues or the chemokine fold. Thus, important receptor binding motifs yet have to be characterized. This lecture will give an overview of the mechanisms underlying “molecular hijacking” of classical chemokine receptors by innate chemokines, featuring their pathophysiological role. Examples will encompass high mobility group binding protein-1 (HMGB1), macrophage migration inhibitory factor (MIF), MIF-2/D-DT and certain β-defensins. Receptor usage, binding domains, signaling, innate immune cell regulation and involvement in various inflammatory conditions, including atherosclerosis will be discussed. The lecture will outline strategies to target such mediators in disease either in conjunction or explicit exclusion of the co-targeting of classical chemokines. Finally, a cross kingdom analysis will be shared offering more general understanding of some of these mediators.
Keynote Forum
Andreas Weinhausel
Austrian Institute of Technology GmbH, Austria
Keynote: Immunomics using protein and peptide microarrays for (cancer) biomarker development
Time : 11:15-11:45
Biography:
Andreas Weinhausel is a Biotechnologist and Specialist in Human Genetics. He has more than 20 years experience in molecular diagnostics. He has worked at the Children’s Cancer Research Institute, Vienna (1995-2004); he specialized in human molecular genetics diagnostics of syndromal and hereditary neoplastic disease. Since 2004, he has been working in the “Molecular Diagnostics” unit at the AIT-Austrian Institute of Technology and his focus is on DNA-methylation and protein biomarker development for cancerous and other systemic human disease using omics discovery and high throughput validation technologies. He is also an Associate Professor for Molecular Biology at the University of Natural Resources and Applied Life Sciences, Vienna.
Abstract:
An estimated 2.7 million new cancer cases and 7.6 million cancer related deaths were reported worldwide in 2008 and incidences are increasing. It is well accepted that early cancer diagnosis can improve survival, thus there is a great need and anticipation to identify novel biomarkers for cancer diagnosis at the earliest possible stage, which can ideally be integrated in minimal-invasive diagnostic assays. Cancer onset and progression produces mutated or aberrantly expressed proteins generally also termed as tumor associated antigens (TAAs) which are able to act as antigens and evoke an immune response which results in the production of autoantibodies. These autoantibodies can be detected months or years before the clinical diagnosis of cancer and can therefore be used as biomarkers for the early diagnosis of cancer. We have setup immunomics discovery technologies using high density protein and peptide microarrays for elucidation of novel biomarkers. By microarray discovery we have defined cancer specific classifiers with high diagnostic performance, obtaining AUCs>0.9 for the big 4 cancer entities. Autoantibody based strategies outperform the current clinical diagnostic methods and would be of high value for improving cancer diagnostics and patient management. To transfer assays onto clinical applicable formats our current developments of different technological variant settings using medium scaled multiplexed assays in microarray and bead array formats will be presented.
Keynote Forum
Walter Schubert
ToposNomos Ltd., Germany
Keynote: The human toponome project: Translating the spatial protein network code into efficient therapies
Time : 11:45-12:15
Biography:
Walter Schubert is founder and director of the international human toponome Project, and he is the head of the Molecular Pattern Recognition Research (MPRR) group at the Medical Faculty of the Otto-von-Guericke-University, Magdeburg, Germany, and guest Professor for Toponomics at the Max-Planck-CAS (CAS-MPG) partner Institute for computational biology, Shanghai, China. Walter Schubert has studied medicine at the universities of Aachen and Bonn, Germany, and has led the neuromuscular diagnostic center at the university of Bonn. He has invented and developed during his clinical work the toponome imaging robot technology MELC/TIS in 1990 (to decipher the protein networks in humans), is co-initiator of the course of studies in computervisualistics (CV) at Magdeburg university (MDU), and teaches human biology for students in CV and medicine at the MDU. Walter Schubert holds many patents, has received several national and international awards and honours, such as the american ISAC best paper award 2008 (for the three symbol code of organized proteomes, "toponome"), and has launched the human toponome project aiming at the functional decoding of the protein networks in humans.rnrnHe is keynote speaker at international congresses (presenting the human toponome project), invited distinguished lecturer at the Case Western Reserve University (2010), and member of several american and european editorial and scientific advisory boards. WS chaired three interdisciplinary national joint projects of the Deutsche Forschungsgemeinschaft and the BMBF (at MDU, and transnational) connecting engineering, informatics, medicine and cell biology in the field of toponomics. The work of the his Magdeburg group and coworkers has been acknowledged by a Research Highlight "Mapping togetherness" (Nature 443, p 609, 2006).rnrn
Abstract:
Imaging cycler® technology (IC®M) is presented as key thenology for (i) the spatial resolution of large protein networks at the target sites of disese with a discriminatory power for an unlimited number or proteins at a time (dimension unlimited imaging); (ii) for the in situ detection of thousands of distinct multi protein complexes; (iii) for the construction of machines able to decode the mechanism of cell invasion into organs, such as the invasion of autoimmune cells and cancer cells, and (iv) application of this technology for the efficient finding of therapies selectively blocking these invasions. The example of amyotrophic lateral sclerosis (ALS) is presented showing that (i) “ALS cells” were seen by IC® for the first time in the blood, (ii) the mechanism of CNS invasion and pathogenic neuronal axotomy of these cells was completely decoded by IC®, and (iv) these “ALS cells” were efficiently depleted in blood of patients. This ALS example can be translated for other diseases based on cell invasion. The IC® detection of somatotopic coding in the innate immune system is key.
- Track 8: Infectious Diseases and Immune System
Track 9: Reproductive Immunology
Track 10: Auto Immunity
Track 13: Diagnostic Immunology
Track 14:Allergy and Therapathies
Track 15:Technological Innovations in Immunology