Day 2 :
Keynote Forum
Sylviane Muller
University of Strasbourg, France
Keynote: Autophagy pathway as a target of therapeutic P140 peptide used in lupus
Biography:
Sylviane Muller has received her Doctoral degrees in Molecular Biology (1978) and Science (1984) from the University of Strasbourg, France. She has worked
as a Post-doctoral Fellow at the Max-Planck Institute for Immunobiology in Freiburg, Germany. She is currently a Distinguished class Research Director at the
CNRS and Professor at the Institute of Advanced Studies of the Strasbourg University (Chair Therapeutic Immunology). She is a Deputy Director of the Molecular
and Cellular Biology Institute, Director of the CNRS Unit Immunopathology and Therapeutic Chemistry and Head of the Drug Discovery Center for Cancer and
Inflammation. Medal is awarded 'Laboratory of Excellence’. Her research interests focus on molecular and cellular events involved in autoimmunity, especially in
the lupus disease. She has discovered the P140/Lupuzor peptide that is currently evaluated in a phase III clinical trial for lupus. She is the co-author of over 345
publications, Co-Inventor of ~30 patents and Co-Founder of NeoMPS (1986) and ImmuPharma (2002) companies. She has received the CNRS Silver Medal (2009)
and the CNRS Innovation Award (2015). Her research interests include molecular and cellular events involved in autoimmunity, especially in the lupus disease.
Abstract:
P140 is a 21-mer peptide (sequence 131-151, phosphorylated at position 140) that is derived from the spliceosomal protein
U1-70K. In a multicenter, randomized, placebo-controlled phase IIb study, P140/Lupuzor™ had no adverse safety signals
and met its primary efficacy end points in lupus patients. These results confirm data generated in MRL/lpr lupus-prone mice in
which the preclinical studies were performed. We found previously that P140 reduces autophagic flux in MRL/lpr B cells and
that macroautophagy (the best characterized type of autophagy) is abnormally enhanced in T-lymphocytes from lupus mice and
patients. More recently, we discovered that in MRL/lpr mice, P140 more precisely targets a selective form of autophagy, called
chaperone-mediated autophagy. We deciphered the successive steps of P140 action leading in fine to a decay of endogenous
antigen processing and loading to MHCII molecules and as a consequence, to a lower activation of auto-reactive T cells. Here,
the mechanism of action of P140 was further studied in the peripheral cells from normal and lupus individuals. As in MRL/
lpr mice, P140 enters human B cells via a clathrin-dependent endo-lysosomal pathway and induces a decrease of MHCII cell
surface expression. It affected autophagy processes in human B cells but did not induce apoptosis of B cells from healthy or
lupus patients. These findings and others provide strong arguments to conclude that the mechanism of action of P140 peptide
is similar in MRL/lpr mice and lupus patients. These results shed light on mechanisms by which P140/Lupuzor modulates
lupus disease in humans affected by this disorder.
Keynote Forum
Itshak Golan
D&D Novel Therapeutics Ltd., UK
Keynote: The role of CD44 and its ligand galectin-8 in the induction of apoptosis in the arthritic joints: Routes to new therapies for autoimmune and cancer diseases
Biography:
Itshak Golan has completed his PhD in Cell Research and Immunology, Tel-Aviv University and Postdoctoral studies in Hebrew University Medical School of
Jerusalem and B.T.G. Israel Ltd. He was the Lecturer in Hebrew University Medical School, Honorary Principal Research Fellow in Imperial College, Honorary
Senior Lecturer in College of Medicine, Swansea University, R&D/Innovation Manager in Swansea University and Senior Program Manager in NIHR. He is a
Founder and Director of two British Biotechnology Companies developing new biological drugs for autoimmune inflammatory diseases and cancer and serving
as an Expert/Projects Evaluator in EU Commission in Brussels. He was awarded for his professional success by Hebrew University and EU Commission. He has
published 15 papers in scientific journals, has 36 patents in the field of rheumatoid arthritis and cancer and has been serving as an Editorial Board Member of MOJ
Immunology.
Abstract:
Autoimmune inflammatory and cancer diseases are intractable disorders, involving pathological activities mediating tissue
destruction. In Europe, and other parts of the world, these diseases cause immense human suffering and inflict on society
an annual economic burden of hundreds of billions of euros, associated with direct and indirect medical costs resulting from
lost work time, disability payments and premature death. Traditional treatments and drugs for various autoimmune and cancer
diseases either produce undesirable side effects or provide a relief of symptoms or delay in deterioration rather than a cure. Most,
if not all, have the deleterious effect of destroying normal cells as well as the cells involved in pathological activities. Results of
efforts made to develop improved treatments for autoimmune and cancer diseases using disease specific cell surface chemical
entities have been disappointing until now. Rheumatoid arthritis (RA) is a common chronic inflammatory arthropathy, leading
to joint destruction and disability as a consequence of the chronic inflammatory processes. The etiology is unknown and the
pathogenesis of this disorder is not well understood, yet the molecular events leading to tissue inflammation resulting with
cartilage and bone destruction are now better defined. As a result there is a better chance now than ever before to develop new
therapeutic modalities; an example of such an effort will be presented here. We have found new variant of human galectin-8
protein expressed in the joints of arthritic patients. This protein induces apoptosis in treated cells and has approximately 80%
therapeutic effect in CIA mouse model.
Keynote Forum
Itshak Golan
D&D Novel Therapeutics Ltd., UK
Keynote: The role of CD44 and its ligand galectin-8 in the induction of apoptosis in the arthritic joints: Routes to new therapies for autoimmune and cancer diseases
Time : 10:00-10:30
Biography:
Itshak Golan has completed his PhD in Cell Research and Immunology, Tel-Aviv University and Postdoctoral studies in Hebrew University Medical School of
Jerusalem and B.T.G. Israel Ltd. He was the Lecturer in Hebrew University Medical School, Honorary Principal Research Fellow in Imperial College, Honorary
Senior Lecturer in College of Medicine, Swansea University, R&D/Innovation Manager in Swansea University and Senior Program Manager in NIHR. He is a
Founder and Director of two British Biotechnology Companies developing new biological drugs for autoimmune inflammatory diseases and cancer and serving
as an Expert/Projects Evaluator in EU Commission in Brussels. He was awarded for his professional success by Hebrew University and EU Commission. He has
published 15 papers in scientific journals, has 36 patents in the field of rheumatoid arthritis and cancer and has been serving as an Editorial Board Member of MOJ
Immunology.
Abstract:
Autoimmune inflammatory and cancer diseases are intractable disorders, involving pathological activities mediating tissue
destruction. In Europe, and other parts of the world, these diseases cause immense human suffering and inflict on society
an annual economic burden of hundreds of billions of euros, associated with direct and indirect medical costs resulting from
lost work time, disability payments and premature death. Traditional treatments and drugs for various autoimmune and cancer
diseases either produce undesirable side effects or provide a relief of symptoms or delay in deterioration rather than a cure. Most,
if not all, have the deleterious effect of destroying normal cells as well as the cells involved in pathological activities. Results of
efforts made to develop improved treatments for autoimmune and cancer diseases using disease specific cell surface chemical
entities have been disappointing until now. Rheumatoid arthritis (RA) is a common chronic inflammatory arthropathy, leading
to joint destruction and disability as a consequence of the chronic inflammatory processes. The etiology is unknown and the
pathogenesis of this disorder is not well understood, yet the molecular events leading to tissue inflammation resulting with
cartilage and bone destruction are now better defined. As a result there is a better chance now than ever before to develop new
therapeutic modalities; an example of such an effort will be presented here. We have found new variant of human galectin-8
protein expressed in the joints of arthritic patients. This protein induces apoptosis in treated cells and has approximately 80%
therapeutic effect in CIA mouse model.
- Workshop
Session Introduction
Herbert B Allen
Drexel University College of Medicine, USA
Title: Autoimmunity: Treatment principles
Biography:
Herbert B Allen has received his MD degree from Johns Hopkins where he did his Internship. His has completed his Residency at the Naval Regional Medical Center in Philadelphia, PA, USA. He was in practice for 27 years, served as a Clinical Assistant and Associate Professor at the University of Pennsylvania, Hahnemann University and currently at Drexel University College of Medicine for over 20 years. He has been the Professor and Chair of Dermatology at Drexel
for the past 14 years.
Abstract:
The proposed treatments for three representative diseases (atopic dermatitis, psoriasis and Alzheimer’s disease) will be presented. All three are caused by chronic microbial states but none is a classic infection. For atopic dermatitis which is initiated by normal flora staphylococci that make biofilms and occlude sweat ducts, no antibiotic treatment is necessary unless the lesions are secondarily infected. In psoriasis, continual low dose penicillin (or pulse azithromycin) is necessary to prevent the streptococci from interacting with the adaptive immune system. In Alzheimer’s disease, where spirochetes make biofilms and the innate immune system is involved, it is most important to treat the microbes before they get to the brain (pre-dental surgery for example) or before they create damage (make biofilms).
- Autoimmunity & Transplantation | Antibodies: Engineering & Therapeutics | Immunodeficiency & Autoimmunity | Clinical Autoimmunity: Current & Future Research | Autoimmune Treatment
Session Introduction
Alessandro Antonelli
University of Pisa, Italy
Title: New therapies for thyroid autoimmune diseases and Graves’ ophthalmopathy
Biography:
Alessandro Antonelli has completed his degree in Medicine in 1982, Specialization in Endocrinology in 1985, Specialization in Occupational Health in 1987 and Specialization in Oncology in 1992 at the University of Pisa, Italy. He is currently an Associate Professor in the Department of Clinical and Experimental Medicine at the University of Pisa. His researches have been published more than 260 articles in international journals (Impact Factor >850). He also serves as an Editorial Board Member and as a Referee and Reviewer of many scientific international journals.
Abstract:
The C-X-C chemokine receptor (CXCR)3 and its IFN-γ dependent chemokines (CXCL9, CXCL10, CXCL11) are involved in the pathogenesis of autoimmune thyroiditis (AT), Graves’ Disease (GD) and Graves’ Ophthalmopathy (GO). IFN-γ induces the above mentioned chemokines secretion by thyrocytes, orbital fibroblasts and preadipocytes. Th1 lymphocytes recruitment in tissue increase IFN-γ production, enhancing the IFN-γ inducible chemokines tissue secretion and leading to the beginning and perpetuation of the autoimmune process. High levels of circulating IFN-γ inducible chemokines have been shown in patients with AT (overall with hypothyroidism) and in GD and GO patients particularly in the active phase. Peroxisome proliferator-activated receptor (PPAR) -γ or -α agonists exert a modulatory role on CXCR3 chemokines in AT, GD and GO. Also methimazole and corticosteroids have an immuno-modulatory effect on CXCR3 chemokines in GD. Additional studies are ongoing to explore the use of new molecules acting as antagonists of CXCR3 or that block CXCL10 in HT, GD and GO. Recently novel agents targeting the various agents involved in the pathogenesis of GO have been proposed as an alternative to corticosteroids. A randomized trial with Rituximab suggests good efficacy with a relative well tolerated profile in patients with active GO. However discordant results have been reported too. Small antagonists of thyroid stimulating hormone receptor molecules (interacting with the receptor on thyrocytes and fibroblasts), the anti-IGF-1 receptor antibody teprotumumab and tocilizumab (an anti-soluble interleukin-6 receptor) in GO has given hoping results. Randomized and controlled studies are needed to generalize these interesting results.
Agnieszka Pozdzik
Erasmus Hospital, Belgium
Title: Auto-immune membranous nephropathy and circulating short-living plasmablasts
Biography:
Agnieszka Pozdzik has completed her Medical study from University School of Medicine, Lublin, Poland and has completed her PhD from Université Libre de Bruxelles, Brussels, Belgium. She is a Nephrologist and an Associate Professor at the Department of Nephrology. Since 2012, she is the Manager of the "Biobank of chronic kidney disease and urinary tract"(MARENVU) and of the Multidisciplinary Center of Nephrolithiasis. She has published more than 20 research papers in reputed journals and has been serving as a Reviewer of repute journals.
Abstract:
Membranous nephropathy (MN) is a kidney specific autoimmune disease mainly mediated by anti-phospholipase A2 receptor 1 autoantibody (PLA2R1 Ab). The adequate assessment of chimeric anti-CD20 monoclonal antibody, rituximab (RTX) efficacy is still needed to improve clinical outcome of patient with MN. We evaluated the modification of plasmablasts (CD3-CD19+CD20-IgD-CD27highCD38high), a useful biomarker of RTX response in other autoimmune diseases, memory (CD3- CD19+CD20+IgD-CD27+CD38-) and naive (CD3-CD19+CD20+IgD+CD27-CD38low) B cells by fluorescence-activated cell sorter analysis in PLA2R1 related MN in one patient during 4-years of follow-up after RTX. RTX induced complete disappearance of CD19+ B cells, plasmablasts and memory B cells as soon as day 15. Despite of severe CD19+ lymphopenia, plasmablasts and memory B cells re-emerged early before naive B cells (days 45, 90 and 120, respectively). During the follow-up, plasmablasts decreased more rapidly than memory B cells but remained still elevated as compared to Day 0 of RTX. Concomitantly, anti- PLA2R1 Ab increased progressively. Our single case report suggests that besides monitoring of serum anti-PLA2R1 Ab level, enumeration of circulating plasmablasts and memory B cells represents an attractive and complementary tool to assess immunological activity and efficacy of RTX induced B cells depletion in anti-PLA2R1 Ab related MN.