Shoenfeld, Yehuda

Profesor dr. Yehuda Shoenfeld se je rodil 14. februarja 1948 v Topolčanih na Slovaškem in se s starši še istega leta preselil v Izrael, kjer je odraščal in se šolal. Študij medicine je zaključil 1972 na Medicinski fakulteti Hadasa Hebrejske univerze v Jeruzalemu (Hebrew University-Hadassah Medical School). Izpopolnjeval se je v Duarteju v Kaliforniji, Bostonu in New Yorku. Deloval je na različnih univerzah in medicinskih institucijah v Izraelu. Od 1984 je vodja Oddelka za medicino, po 1985 pa tudi Centra za avtoimune bolezni Medicinskega centra Sheba, največje izraelske bolnišnice, ki je pridružena Sacklerjevi medicinski fakulteti Univerze v Tel-Avivu. Na tej univerzi je od leta 1990 redni profesor.
Profesor Shoenfeld je bil za dopisnega člana Slovenske akademije znanosti in umetnosti izvoljen maja 2009.
Prof. Shoenfeld je eden vodilnih svetovnih strokovnjakov na področju študija imunsko odvisnih bolezni, predvsem s področja avtoimunosti. Njegovo klinično in znanstveno delo je privedlo do več kot 1550 objav v mednarodnih znanstvenih revijah, med njimi v New England Journal of Medicine, Lancet, Proceedings of the National Academy of Sciences USA, Journal of Clinical Investigations, Journal of Immunology, Blood, Journal of Experimental Medicine, Circulation in Cancer. Njegova dela so citirana več kot 20000 krat. Napisal in uredil je 25 knjig, med katerimi so nekatere kot sta na primer The Mosaic of Autoimmunity in Infections and Autoimmunity postale temeljni kamni znanosti in klinike. Napisal je tudi učbenik Autoantibodies. Je član uredniških odborov 43 revij na področju revmatologije in avtoimunosti ter ustanovitelj in urednik revije Israel Medical Association Journal) ter revije Autoimmunity Reviews, pri reviji Journal of Autoimmunity pa je sourednik. Napisal je več kot 350 poglavij v knjigah. Uredil je enciklopedijo v desetih knjigah Israeli Medical Encyclopedia, pri pripravi katere je sodelovalo 1200 zdravnikov. Prof. Shoenfeld je član 14 mednarodnih organizacij s področja imunologije, interne medicine, revmatologije in onkologije.
Organiziral je več kot 15 mednarodnih sestankov po vsem svetu. Kot zanimiv predavatelj je imel veliko uvodnih predavanj na mednarodnih znanstvenih srečanjih in je bil povabljen za gostujočega profesorja na mnogih institucijah po celem svetu. Je član Izraelskega društva za alergijo in klinično imunologijo, ki mu je v letih 2000–2002 tudi predsedoval. Za svoje raziskave na področju klinične in eksperimentalne revmatologije je prof. Shoenfeld leta 2004 prejel nagrado Carol Nachman Award for Rheumatology. Leto pozneje je na Dunaju prejel nagrado EULAR Prize 2005. Leta 2006 je za svoje zasluge za izraelsko-slovaško znanstveno sodelovanje prejel zlato medaljo. Nedavno je tudi postal častni član Madžarskega revmatološkega združenja, na Kalifornijski univerzi v Davisu pa je prejel nagrado Nelson´s Prize for Humanity and Science.
Na področju imunsko odvisnih bolezni in avtoimunosti je prof. Shoenfeld v zadnjih treh desetletjih sam in s svojimi sodelavci odločilno zaznamoval tako osnovne raziskave kot terapevtske možnosti. Pozornost je vzbudil že v začetku 80 let prejšnjega stoletja, ko je pridobil prvo človeško monoklonsko protitelo proti DNK. Dostopnost teh protiteles je omogočila raziskave patogenih idiotipov, še posebej idiotipa 16/6. Najprej je s pomočjo imunizacije s patogenimi idiotipi razvil živalski model sistemskega lupusa eritematozusa, kasneje pa tudi drugih avtoimunskih bolezni. Prof. Shoenfeld je nadalje prvi opozoril na patogenetsko vlogo antifosfolipidnih protiteles. Dokazal je imunogeno vlogo beta2-glikoproteina I in možnost razvoja antifosfolipidnega sindroma z aktivno imunizacijo živali s tem proteinskim kofaktorjem. Model se uporablja po vsem svetu za raziskave patogenih mehanizmov in možnosti zdravljenja. Raziskal je tri peptide na molekuli beta2-glikoproteina I, s katerimi je po sistemski aplikaciji lahko zavrl bolezen. Enako mu je uspelo tudi z oralno toleranco na celotni protein. Z dodatnim raziskovanjem peptidov na molekuli beta2-glikoproteina I, ki jih pogosto najdemo na bakterijah in virusih, je trdneje povezal okužbo z antifosfolipidnim sindromom, še posebej s katastrofično varianto te bolezni. Prof. Shoenfeld je pomembno zaznamoval tudi raziskave s področja vaskulitisov z opredelitvijo patogene vloge antiendotelijskih protiteles. Na živalskih modelih je tudi prikazal, da protitelesa proti citoplazmi nevtrofilcev izzovejo vaskulitične spremembe na različnih organih. Prof. Shoenfeld je odigral pionirsko vlogo pri opredelitvi ateroskleroze kot avtoimunske bolezni. Dokazal je, da protein toplotnega šoka 65 in beta2-glikoprotein I sprožita bolezen pri živalih, medtem ko oksidirani LDL delujejo zaviralno. Zgornjo ugotovitev je podkrepil s prenosom limfocitov z obolele živali na zdravo. Pomembna je tudi vloga prof. Shoenfelda pri raziskavah odnosa med rakastimi in avtoimunskimi boleznimi, med cepljenji in avtoimunostjo ter pri teoretičnih razmišljanjih o zdravljenju avtoimunskih in rakastih bolezni s sistemsko apliciranimi hiperimunskimi globulini gama.
Prof. Shoenfeld že več kot 20 let sodeluje s slovenskimi raziskovalci. Rezultat sodelovanja med Oddelkom za revmatologijo Kliničnega centra v Ljubljani in oddelkom, ki ga vodi v Izraelu, je preko 30 skupnih publikacij v uglednih mednarodnih revijah. Leta 1999 je dobil častni naziv Gostujoči profesor Medicinske fakultete v Ljubljani, leta 2006 pa je postal častni član Revmatološke sekcije Slovenskega zdravniškega društva.
Kot je iz vsega povedanega razvidno, je profesor dr. Yehuda Shoenfeld svetovno priznan strokovnjak z enkratnim publicističnim opusom na področju medicinskih znanosti in klinike. Ima tudi velike zasluge pri razvoju slovenske revmatologije in imunologije.

1. Shoenfeld Y, Hsu-Lin SC, Gabriel JE, Silberstein LE, Furie BC, Furie B, Stollar BD, Schwartz RS. Production of monoclonal autoantibodies by human-human hybridomas. J Clin Invest 70:205-208, 1982.
2. Shoenfeld Y, Rauch J, Massicotte H, Datta SK, Schwartz JA, Stollar BD, Schwartz RS. Polyspecificity of monoclonal lupus autoantibodies produced by human-human hybridomas. New Eng J Med 308:414-420, 1983.
3. Shoenfeld Y, Isenberg DA, Rauch J, Madaio MP, Stollar BD, Schwartz RS. Idiotypic cross reactions of monoclonal Shoenfeld Y, Schwartz RS. Genetic and immunologic factors in autoimmune diseases. New Eng J Med 311:1019-1029, 1984.
4. Shoenfeld Y, Mozes E. Pathogenic idiotypes of antibodies and autoimmunity: A lesson from a new syndrome of experimental SLE. FASEB J 4:2646-2651, 1990.
5. Blank M, Cohen J, Toder V, Shoenfeld Y. Induction of anti-phospholipid syndrome by passive transfer of anti-cardiolipin antibodies. Proc Nat Acad Sci 88:3069-3073, 1991.
6. Bakimer R, Fishman P, Blank M, Sredni B, Djaldetti M, Shoenfeld Y. Induction of primary antiphospholipid syndrome in mice by immunization with a human monoclonal anticardiolipin antibody (H-3). J Clin Invest 89:1558-1663, 1992.
7. Shoenfeld Y. Idiotypic induction of autoimmunity: a new aspect of the idiotypic network. FASEB J 8:1296-1301, 1994.
8. Hojnik M, George J, Ziporen L, Shoenfeld Y. Heart valve involvement (Libman-Sacks endocarditis) in the antiphospholipid syndrome. Circulation 93: 1574 - 1587, 1996.
9. Ziporen L. Shoenfeld Y. Levy Y, Korcyn AD. Neurological dysfunction and hyperactive behavior associated with antiphospholipid syndrome: a mouse model. J Clin Invest 100:613-619, 1997.
10. George J, Blank M, Levy Y, Meroni PL, Damianovich M, Tiniani A, Shoenfeld Y. Differential effects of anti--glycoprotein I antibodies on endothelial cells and on the manifestations of experimental antiphospholipid syndrome. Circulation 97: 900-906, 1998.
11. Blank M, Shoenfeld Y, Cabilly S, Heldman Y, Fridkin M, Katchalski-Katzir E. Prevention of experimental antiphospholipid syndrome and endothelial cell activation by synthetic peptides. Proc Nat Acad Sci (USA) 96: 5164-5168, 1999.
12. George J, Harats D, Gilbourd B, Afek A, Levy Y, Schneiderman J, Barshack I, Kopolovic J, Shoenfeld Y. Immunolocalization of beta2-Glycoprotein I (Apolipoprotein H) to human atherosclerosis plaques: potential implications for lesion progression. Circulation 99: 2227-2230, 1999.
13. Blank M, Krause aI, Fridkin M, Keller N, Kopolovic J, Goldberg I, Tobar A, Shoenfeld Y. Bacterial I induction of autoantibodies to β2-glycoprotein-I accounts for the infectious etiology of antiphospholipid syndrome. J Clin Invest 109: 797-804, 2002.
14. Shoenfeld Y, Gerli R, Doria A, Matsuura E, Cerinic MM, Ronda N, Jara LJ, Abu-Shakra M, Meroni PL, Sherer Y. Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation 112: 3337-3347, 2005.
15. Shoenfeld Y, Agmon-Levin N. 'ASIA' – autoimmune / inflammatory syndrome induced
by adjuvants. J Autoimmun 36: 4-8, 2011

(junij 2011)

Yehuda Shoenfeld is the head of the Department of Medicine since 1984 (age 36) at the largest hospital in Israel- the Sheba Medical Center, which is affiliated to the Sackler Faculty of Medicine in Tel-Aviv University, in which Dr. Shoenfeld is the Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases. He has founded and is heading the Center for Autoimmune Diseases since 1984. His clinical and scientific works focus on autoimmune /rheumatic diseases, and he has published more than 1550 papers in journals such as New Eng J Med, Lancet, Proc Nat Acad Scie, Nature, J Clin Invest, J Immunol, Blood, J Exp Med, Circulation, Cancer and others. He has authored and edited 25 books, some of which became cornerstones in science and clinical practice, such as "The Mosaic of Autoimmunity", "Infections and Autoimmunity", the textbooks "Autoantibodies", and "Criteria for diagnosis of autoimmune diseases", which were sold by the thousands. He is on the editorial board of 43 journals in the field of rheumatology, and autoimmunity and is the founder and the Editor of the "IMAJ" (Israel Medical Association Journal, 1997) the representative journal of science and medicine in the English language in Israel and also is the founder and Editor of the "Autoimmunity Reviews" (Elsevier, 2001, IF=5.4), and Co-Editor of "Journal of Autoimmunity" (IF=9.2). He has written more than three hundreds and fifty chapters in books.
Dr. Shoenfeld is the member of the Israel Association of Allergy and Clinical Immuology and served as the president of the society in the years 2000-2002.
Dr. Shoenfeld is an attractive lecturer and is invited all over the world to deliver plenary lectures (was several times the award of the best lecturer) and also has been a visiting professor to many institutions all over the globe.

Scientific contributions: Dr Shoenfeld has started the field of Human monoclonal autoantibodies in the year 1980 generating the first human monoclonal anti-DNA autoantibodies (JCI 1982.NEJM ,1983). The availability of these human Mabs enabled the extension of the field to the analysis of the pathogenic idiotypes and specifically of the 16/6 idiotype of anti-DNA antibodies(J Exp Med 1983). More than 100 papers were reported on this interesting idiotype. One of his major contributions to the field of autoimmunity and rheumatology was the induction of experimental models of SLE upon idiotypic immunization (Proc Nat Acad Scie 1988), a field which was extended later on to anti-phospholipid syndrome (APS), vasculitis, Goodpasture's and thyroiditis. These models led to the theory of the Autoantibody Spread (The Immunologist 2000) to explain the existence of so many and diverse autoantibodies in systemic autoimmune rheumatic diseases, despite restriction to the disease. The work on idiotypes was summarized in the books: Idiotypes in Autoimmunity and Cancer and Infection (co-edited by him and E. Gershwin), and in the textbook of Autoantibodies (with J. Peter).
Dr. Shoenfeld's group was the first to show the pathogenic role of the antiphospholipid antibodies (Proc Nat Acad Scie 1991).Their model of experimental APS is in use worldwide and is employed to study pathogenic mechanisms as well as new therapeutic modalities in this syndrome. Their studies were summarized in the books co-edited by him on the Antiphospholipid Syndrome (CRC press 1998, Elsevier 2002).

Dr. Shoenfeld was the first to show the immunogenicity of β2GPI and the ability to induce APS upon active immunization of mice with this cofactor. Employing the phage library display technique, 3 peptides residing on the B2GPI molecule were detected, showing their preventive capacity in this syndrome (Proc Nat Acad Scie 1999). Additional remarkable novel therapeutic suggestions in APS were reported by his group and entail interleukin-3 (JCI 1993), oral tolerance with β2GPI (J Immunol 1999) and others. Dr. Shoenfeld also expanded our knowledge on bone marrow transplantation for autoimmunity and its potential ability to transfer autoimmune conditions.
Recently, Dr Shoenfeld became a pioneer and a leader in the new field of atherosclerosis as an autoimmune disease, confirming the ability of HSP65 and B2GPI to induce the disease in animal models and oxLDL to prevent it, and many of his contributions were recently reported in several issues of Circulation (1998- 2000). He provided the ultimate evidence for autoimmunity in atherosclerosis by passive transfer of the disease with lymphocytes to naive animals (Circulation 2000, Trends in Immunol 2001, J Am Coll Card 2001 and 2002). Several of his reports relate to the pathogenic role of anti-endothelial antibodies (AECA) (Arthritis & Rheum 2001) and ANCA showing their potential to induce vasculitic lesions in animal models. His clinical experience has been devoted to the employment of IVIG for the treatment of many autoimmune disease (Lupus 1999-2000). He reported on the ability of IVIG to prevent metastatic spread (Int Immunol 1999) and carries out the clinical studies in this area (Cancer 2002; Ann NY Acad Sci 2008).
Additional fields in which Dr Shoenfeld had an imprints on include the aspects of vaccination induced autoimmune diseases (J Autoimmunity 2000; Nature Rheumatology 2009) and the bi-directional relationship between cancer and autoimmunity (summarized in the book: Cancer and Autoimmunity (Elsevier, 2000), and Infection and Autoimmunity (Trends in Immunology, 2009).
Theories which are referred to Dr. Shoenfeld entail: the Mosaic of Autoimmunity, the Kaleidoscope of Autoimmunity, and the Autoantibody Spread. His scientific works were cited in the literature more than 20,000 times (Citation Index).
Dr. Shoenfeld has organized several remarkable international meetings including The 4th international congress of SLE in Jerusalem(1995), The 2nd international congress of Autoimmunity in Tel-Aviv (1999), The meeting on the Immune system and Atherosclerosis Conference in Geneva (Switzerland) 2001, The 3rd International Congress of Autoimmunity, Geneva, February 2002, The 10th International Congress on Anti-Phospholipid Syndrome, Sicily, October 2002, The 4th International Congress of Autoimmunity, Budapest, October 2004, Singapore International Scientific Meeting on Arthritis & Rheumatology, November 2004, Vaccination, Infection and Autoimmunity: Myth and Reality – VIAMR 2005, October 2005, Lausanne (Switzerland), 2nd Asian Autoimmunity meeting Hong-Kong, March 2006, and 2nd Latino-American Congress of Autoimmunity, Rio de Janeiro, Brazil, April 2006. The 6th International Congress on Autoimmunity 2008 in Porto, Portugal, attracted close to 2000 autoimmunologists from 57 countries, The Asian Congress on Autoimmunity Singapore 2009, and coming The 7th International Congress on Autoimmunity in Ljubljana, Slovenia, 2010).

Dr. Shoenfeld received the Carol Nachman Award for Rheumatology 2004 for outstanding innovative research work in the field of clinical and experimental rheumatology.
Dr. Shoenfeld received in Vienna, Austria, the EULAR prize 2005: "The infectious etiology of anti-phospholipid syndrome". In UC Davis, USA Dr. Shoenfeld received the Nelson's Prize for Humanity and Science for 2008. In 2009 he was honored as Doctoris Honoris Causa, from Debrecen University (Hungary).
On March 2006 Dr. Shoenfeld has received a gold medal from the Slovak Society of Physicians for his contribution to Israel – Slovakia collaboration, in 2008 he became an honorary member of the Hungarian Association of Rheumatology, and in May 21, 2009 he became in Ljubljana, Slovenia, an Associate Member of the Slovenian Academy of Science and Arts,
In 2008 Dr. Shoenfeld edited the Israeli Medical Encyclopedia, a 10 volumes edition, written by 1200 physicians.
Dr. Shoenfeld has educated a long list of students being heads of departments and institutes.

(August 2010)