Ανάπτυξη νέου µοντέλου παρακολούθησης της δράσης µικροβιακών παραγόντων που επάγουν αυτοανοσία: infectosome Nat Immun 2001 Environment Epigenetic Factors Genes Immune System Biliary Epithelial Cell Destruction – Development of PBC Smyk et al Aut Dis 2011 Gourley M, Miller FW Nat Clin Pract Rheumatol 2007 3(3):172–180 TCR effector T APC MHC IL-10 TGF-β TCR GITR Fo x CTL-4 p3 CD4 Treg CD25 Foxp3 Molecular Mimicry (Μοριακός Μιµητισµός) ‘ ….. viruses encode similar to self antigens, which allow the host to regard an infecting virus as self preventing their elimination by our immune system’ George Snell (1968) ΑΝΟΣΟΛΟΓΙΑ Μοριακός Μιµητισµός: Μηχανισµός που επάγει αυτοανοσία & προκαλεί την ανάπτυξη αυτοάνοσων νοσηµάτων B-cell mimicry Microbial Peptide Homology Self Peptide GAAVLMGMIT GAA.LMGMI. GAAILMGMIG D Bogdanos et al J Hepatol 2002; 2004; 2005; 2008; 2009 Vergani & Bogdanos Hepatol 2004 Ma et al J Immunol 2003; Bogdanos et al J Immunol 2005; Bogdanos et al Gastroenterol 2006; Polymeros et al Gastroenterol 2006; HEPATITIS C VIRUS Non-self LIVER self Gregorio et al J immunol 1999; Gregorio Clin Exp Immunol 2003; Rigopoulou et al Vaccine 2005; Ma et al J Immunol 2002; Bogdanos et al Int J ImmunoPathPharm 2005; Bogdanos et al Gastroenterol 2006; Polymeros et al Gastroenterol 2006; Hepatitis C Virus Molecular mimicry Smooth Muscle autoantigens (myosin, smoothelin) Nuclear Autoantigens J Immunol 1999 2002 (matrin, histone) JJ Immunol Immunol 2003 Hepatology 2003 J Hepatol 2009 Βασικό Μειονέκτηµα Κλινικοεργαστηριακών µελετών: Η µελέτη γίνεται κατά το διάστηµα που έχει ήδη αναπτυχθεί η νόσος GWAS Epigenetic Factors Infectosome E. coli, N. aromaticivorans, L.delbruekii, mycobacteria, C. pneumoniae Genetic Epigenetic f actors PBC Exposome Non-infectious pollution, cigarette smoke, nail polish, hair dyes, hormone replacement therapy, oral contraception X monosomy DR8, DRB1, DQA2, DQA1, DQB1IRF5, STAT4, SPIB, IL12A, IL12RB, CXCR5, MMEL1, FCRL3 Molecular Mimicry Project 1998- 2002 Institute of Hepatology University College London 2003 -2011 Institute of Liver Studies King’s College London EUROPE Biorad CyBio Diarect Euclone EUROIMMUN Generic Assays InnoVision InvitrogenMabTech Mardx Medipan Meridian LS Menarini Miltenyi Molecular Probes PeproTech Phadia Roche AMERICA Gilead INOVA IMCCO Virusys JAPAN MBL Disclosure Statement Acknowledgements King’s College London Professor D Vergani Professor H Baum Professor G Mieli-Vergani Professor B Portmann Dr Y Ma Dr K Choudhuri Dr ET Davies Dr MS Longi Dr F Meda Dr A Koutsoumpas Dr R Mitry Dr S Leoni Dr I Bianchi Dr C Almerighi Dr M Mytilinaiou Dr C Liaskos University of Barcelona Professor Rodes Dr Albert Pares Dr Llorenc Caballeria University College London Professor Williams Professor Forbes Dr Polymeros Dr M Okamoto, Dr UC Sharma Dr D Arioli, Dr R Lopes University of California Professor ME Gershwin Dr Carlo Selmi University of Amsterdam Professor U Beuers University of Toronto Professor J Heathcote Royal Free Hospital Professor AK Burroughs Dr Patrice Butler Dr Alessandro Grasso Dr Paolo Montalto Dr Fulya Gunsar Dr John Vlachogiannakos University of Bologna Professor FB Bianchi Professor Marco Lenzi Dr Luigi Muratori Dr Paolo Muratori University of Thessaly & BIOMED CERETETH Professor GN Dalekos As. Prof EI Rigopoulou Dr Α Mavropoulos Dr MG Mytilinaiou Dr E Spyrou
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