Only in very recent times have therapies been developed that are specific to a particular manifestation of autoimmune disease, and these have begun to replace the all-purpose remedies of the past 30 years. This volume, which draws on the principles of immunology presented in Volume 1050 (Autoimmunity: Concepts and Diagnosis at the Cutting Edge), extends these concepts to the realm of clinical findings and current therapy for many autoimmune and connective tissue disorders. Both organ-specific and organ-nonspecific diseases are covered, and one section is entirely focused on treatment. Treatments using cytokines, chemokines, cognate receptors, and genetic interactions are particularly prominent in these reports, and attention is also paid to the increasing use of intravenous imunoglobulins and both monoclonal and imunosuppressive agents. A therapeutic void remains, but the work reported on here contributes considerably to the effort to fill that void. NOTE: Annals volumes are available for sale as individual books or as a journal. For information on institutional journal subscriptions, please visit www.blackwellpublishing.com/nyas. ACADEMY MEMBERS: Please contact the New York Academy of Sciences directly to place your order (www.nyas.org). Members of the New York Academy of Science receive full-text access to the Annals online and discounts on print volumes. Please visit http://www.nyas.org/MemberCenter/Join.aspx for more information about becoming a member.

Table of Contents:
Foreword: Yehuda Shoenfeld and M. Eric Gershwin. . Part I: Organ-Specific Autoimmune Diseases:. 1. Activation, Apoptosis, and Clearance of Neutrophils in Wegener's Granulomatosis: André P. van Rossum, Pieter C. Limburg, and Cees G. M. Kallenberg. 2. Is PR3-ANCA Formation Initiated in Wegener's Granulomatosis Lesions? Granulomas as Potential Lymphoid Tissue Maintaining Autoantibody Production: J Voswinkel, A Müller, and P Lamprecht. 3. Clinical Relevance of Antiphospholipid Antibodies in Primary Biliary Cirrhosis: Philipp von Landenberg, Michael Baumgartner, Juergen Schoelmerich, Karl J. Lackner, and Reinhild Klein. 4. IL-10 and the Cytokine Network in the Pathogenesis of Human Autoimmune Hemolytic Anemia: Caterina Toriani-Terenzi and Enzo Fagiolo. 5. Crohn's Disease Is Associated with Polymorphism of CARD15/NOD2 Gene in a Hungarian Population: Zsuzsanna Nagy, Oszkár Karádi, György Rumi, György Rumi, Jr., Alajos Pár, Gyula Mózsik, László Czirják, and Gábor Süto. 6. Apoptosis in Human Skin: Role in Pathogenesis of Various Diseases and Relevance for Therapy: Esther Reefman, Pieter C. Limburg, Cees G. M. Kallenberg, and Marc Bijl. 7. Cancer-Associated Myositis: Clinical Features and Prognostic Signs: Andrea Ponyi, Tamás Constantin, Miklós Garami, Csilla andrás, Béla Tállai, Andrea Váncsa, Lajos Gergely, and Katalin Dankó. 8. Control of Type 1 Autoimmune Diabetes by Naturally Occurring CD4+CD25+ Regulatory T Lymphocytes in Neonatal NOD Mice: C A Piccirillo, M Tritt, E Sgouroudis, A Albanese, M Pyzik, and V Hay. 9. The Role of Methallothioneins in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis: Carmen Espejo and Eva M. Martínez-Cáceres. 10. Oxidized Low-Density Lipoprotein/ß2-Glycoprotein I Complexes and Autoantibodies in Patients with Type 2 Diabetes Mellitus: Luis R. Lopez, Beth L. Hurley, Daniel F. Simpson, and Eiji Matsuura. 11. Autoantibodies to Human 6 Integrin in Patients with Bullous Pemphigoid: Mária Kiss, Ádám Perényi, Ilona Marczinovits, János Molnár, Attila Dobozy, Lajos Kemény, and Sándor Husz. 12. Soluble HLA Class I and Class II Molecules in Relapsing-Remitting Multiple Sclerosis: Acute Response to Interferon-ß1a Treatment and Their Use as Markers of Disease Activity: Alireza Minagar, Irena Adamashvilli, Stephen L. Jaffe, Michael F. Glabus, Eduardo Gonzalez-Toledo, and Roger E. Kelley. 13. Proinflammatory Cytokines and Autoimmunity in Churg-Strauss Syndrome: B Hellmich, E Csernok, and W L Gross. 14. Rheumatic Fever: How S. pyogenes-Primed Peripheral T Cells Trigger Heart Valve Lesions: L Guilherme, K C Faé, S E Oshiro, A C Tanaka, P M A Pomerantzeff, and J Kalil. 15. Avidity of Anti-ß2-Glycoprotein I and Thrombosis or Pregnancy Loss in Patients with Antiphospholipid Syndrome: S Cucnik, B Bozic, T Kveder, M Tomsic, and B Rozman. 16. Neurological Complications of Celiac Disease and Autoimmune Mechanisms: Preliminary Data of a Prospective Study in Adult Patients: C Briani, G Zara, E Toffanin, S Ruggero, A Ferrarini, F De Lazzari, M Luca, D Faggian, F Grassivaro, M Ermani, R Pezzani, B Giometto, and A D'odorico. 17. E2F1–/– C57BL/6 Mice Overexpressing a Human Bcl-2 Transgene in B Cells Develop a Mild Autoimmune Syndrome: María J. Marín, Itxaso García, Marta Peña, Ainhoa Bolívar, Ana Zubiaga, and Marcos Lóez-Hoyos. 18. Systemic Thromboembolism in Inflammatory Bowel Disease: Mechanisms and Clinical Applications: Gilad Twig, Gisele Zandman-Goddard, Martine Szyper-Kravitz, and Yehuda Shoenfeld. 19. Pregnancy Loss and Endometriosis: Pathogenic Role of Anti-Laminin-1 Autoantibodies: Junko Inagaki, Akane Kondo, Luis R. Lopez, Yehuda Shoenfeld, and Eiji Matsuura. 20. Primary Biliary Cirrhosis: Solving the Enigma: Alessia Giorgini, Carlo Selmi, Pietro Invernizzi, Mauro Podda, Massimo Zuin, and M Eric Gershwin. 21. The Stages of Type 1A Diabetes: Naru Babaya, Maki Nakayama, and George S. Eisenbarth. 22. Soluble CD40L in Plasma of Patients with Primary Biliary Cirrhosis: Sabine Oertelt, Pietro Invernizzi, Carlo Selmi, Mauro Podda, and M Eric Gershwin. 23. Decreased Serum Leptin Levels in Primary Biliary Cirrhosis: A Link between Metabolism and Autoimmunity?: Roman Rieger, Sabine Oertelt, Carlo Selmi, Pietro Invernizzi, Mauro Podda, and M Eric Gershwin. 24. Analysis of the Foxp3/Scurfin Gene in Crohn's Disease: Ogyi Park, Irina Grishina, Patrick S. Leung, M Eric Gershwin, and T Prindiville. . Part II: Systematic Autoimmune Diseases:. 25. Juvenile Systemic Sclerosis: A Follow-up Study of Eight Patients: Szilvia Szamosi, László Maródi, László Czirják, Zoltán Ellenes, and Gabriella Szücs. 26. Antifodrin Antibodies in Sjögren's Syndrome: A Review: Torsten Witte. 27. Generation and Characterization of Three Monoclonal IgM Antiphospholipid Antibodies Recognizing Different Phospholipid Antigens: Catharina Buschmann, Christian Fischer, Viola Ochsenhirt, Carolin Neukirch, Karl J. Lackner, and Philipp von Landenberg. 28. Premature Immunosenescence in Rheumatoid Arthritis and Multiple Sclerosis Patients: Marielle Thewissen, Loes Linsen, Veerle Somers, Piet Geusens, Jef Raus, and Piet Stinissen. 29. Association of Rheumatoid Arthritis with HLA-DR1 and HLA-DR4 in Hungary: Anikó Kapitány, Erika Zilahi, Sándor Szántó, Gabriella Szücs, Zoltán Szabó, Anikó Végvári, Péter Rass, Sándor Sipka, Gyula Szegedi, and Zoltán Szekanecz. 30. Plasminogen Activator Inhibitor-1 Is Associated with Impaired Endothelial Function in Women with Systemic Lupus Erythematosus: Emily C. Somers, Wendy Marder, Mariana J. Kaplan, Robert D. Brook, and W Joseph McCune. 31. Early Atherosclerosis in Rheumatoid Arthritis: Effects of Smoking on Thickness of the Carotid Artery Intima Media: Roberto Gerli, Yaniv Sherer, Gaetano Vaudo, Giuseppe Schillaci, Boris Gilburd, andrea Giordano, Elena Bartoloni Bocci, Rosita Allegrucci, Simona Marchesi, Elmo Mannarino, and Yehuda Shoenfeld. 32. Investigation of Arthritic Joint Destruction by a Novel Fibroblast-Based Model: U Sack, B Sehm, F Kahlenberg, A Murr, J Lehmann, A Tannapfel, K Uberla, A Moessner, A Dietrich, F Emmrich, F Lange, A Jungel, J-M Braun, and U Anderegg. 33. Prevalence of Antiphospholipid and Antioxidized Low-Density Lipoprotein Antibodies in Rheumatoid Arthritis: Yaniv Sherer, Roberto Gerli, Gaetano Vaudo, Giuseppe Schillaci, Boris Gilburd, andrea Giordano, Elena Bartoloni Bocci, Rosita Allegrucci, Simona Marchesi, Elmo Mannarino, and Yehuda Shoenfeld. 34. Mono-organic versus Multi-organic Involvement in Primary Antiphospholipid Syndrome: Gabriela Medina, Olga Vera-Lastra, Ulises Angeles, and Luis J. Jara. 35. OxLDL/ß2GPI Complexes and Autoantibodies in Patients with Systemic Lupus Erythematosus, Systemic Sclerosis, and Antiphospholipid Syndrome: Pathogenic Implications for Vascular Involvement: Luis R. Lopez, Daniel F. Simpson, Beth L. Hurley, and Eiji Matsuura. 36. Anti-HSP60 Immunity Is Already Associated with Atherosclerosis Early in Life: M Knoflach, D Bernhard, and G Wick. 37. Determinants of Vessel Targeting in Vasculitis: Gary S. Hoffman. 38. Lymphocyte Activation as a Possible Measure of Atherosclerotic Risk in Patients with Sleep Apnea: Larissa Dyugovskaya, Peretz Lavie, and Lena Lavie. 39. Systemic Lupus Erythematosus, Atherosclerosis, and Autoantibodies: Sandra Zampieri, Luca Iaccarino, Anna Ghirardello, Elena Tarricone, Silvia Arienti, Piercarlo Sarzi-Puttini, Pierfranca Gambari, and andrea Doria. 40. Accelerated Atherosclerosis in Patients with Systemic Autoimmune Diseases: Karina de Leeuw, Cees Kallenberg, and Marc Bijl. 41. Nocturnal Hormones and Clinical Rhythms in Rheumatoid Arthritis: Maurizio Cutolo, Kati Otsa, Oivi Aakre, and Alberto Sulli. 42. Xenobiotic-Induced Recruitment of Autoantigens to Nuclear Proteasomes Suggests a Role for Altered Antigen Processing in Scleroderma: Min Chen and Anna von Mikecz. 43. Humoral Antigenic Targets of the Ribosomal P0 Lupus Autoantigen Are Not Limited to the Carboxyl Region: Benjamin F. Bruner, Donny M. Wynn, Morris Reichlin, John B. Harley, and Judith A. James. 44. Clinical Correlations of Potential Activity Markers in Systemic Sclerosis: R Becvár, J Stork, V Pesáková, A Stánová, H Hulejová, L Rysová, A Zatloukalová, P Zatloukal, M Jáchymová, and L Pourová. 45. Complement Activation: A Novel Pathogenic Mechanism in the Antiphospholipid Syndrome: Silvia S. Pierangeli, Mariano Vega-Ostertag, Xiaowei Liu, and Guillermina Girardi. 46. The Interplay of Chemokines and Dendritic Cells in the Pathogenesis of Lupus Nephritis: Marco Tucci, Nicola Calvani, Hanno B. Richards, Cosima Quatraro, and Franco Silvestris. 47. Cellular and Molecular Mechanisms of Regulation of Autoantibody Production in Lupus: Bevra H. Hahn, Fanny Ebling, Ram R. Singh, Ram P. Singh, George Karpouzas, and Antonio La Cava. 48. The Role of Innate and Adaptive Immunity to Oxidized Low-Density Lipoprotein in the Development of Atherosclerosis: Kazuko Kobayashi, Luis R. Lopez, Yehuda Shoenfeld, and Eiji Matsuura. 49. Predictive Markers for Development of Severe Organ Involvement in Patients with Systemic Sclerosis: Laure Ysebrant De Lendonck, Annick Ocmant, Florence Roufosse, and Elie Cogan. 50. Hughes Syndrome, the Antiphospholipid Syndrome: A New Chapter in Neurology: Giovanni Sanna, Maria Laura Bertolaccini, and Graham R. V. Hughes. 51. New Facet of Antiphospholipid Antibodies: Guido Valesini and Cristiano Alessandri. . Part III: Treatment:. 52. Inhibitor Development in Patients with Hemophilia A after Continuous Infusion of FVIII Concentrates: CH von Auer, J Oldenburg, M von Depka, C Escuriola-Ettinghausen, K Kurnik, H Lenk, and I Scharrer. 53. Increased Spontaneous Apoptosis of CD4+CD25+ T Cells in Patients with Active Rheumatoid Arthritis Is Reduced by Infliximab: E Toubi, A Kessel, Z Mahmudov, K Hallas, M Rozenbaum, and I Rosner. 54. Synergistic Effect of Avemar on Proinflammatory Cytokine Production and Ras-Mediated Cell Activation: András Telekes, Endre Kiss-Tóth, Tünde Nagy, Eva E. Qwarnstrom, Erzsébet Kúsz, Timea Polgár, Ákos Resetár, Steven K. Dower, and Erno Duda. 55. Fermented Wheat Germ Extract (Avemar) in the Treatment of Cancer and Autoimmune Diseases: Laszlo G. Boros, Michele Nichelatti, and Yehuda Shoenfeld. 56. Open-Label 24-Month Study Evaluating Infliximab Therapy in Patients with Psoriatic Spondyloarthropathy: J J Scali, A Kaminsky, J Salomón, S Visentini, and E Dancziger. 57. Cyclosporine: From Renal Transplantation to Autoimmune Diseases: Claudio Ponticelli. 58. Autoimmunity and Anti-TNF- Agents: Fabiola Atzeni, Maurizio Turiel, Franco Capsoni, andrea Doria, Pierluigi Meroni, and Piercarlo Sarzi-Puttini. 59. Combination Treatment of Rat Adjuvant-Induced Arthritis with Methotrexate, Probiotic Bacteria Enterococcus faecium, and Selenium: Jozef Rovensky, Karol Svík, Vladimír Matha, Richard Istok, Vojtech Kamarád, Libor Ebringer, Miroslav Ferencík, and Mária Stancíková. 60. Comparative Analysis of Antigen Specificities in the Monomeric and Dimeric Fractions of Intravenous Immunoglobulin: Sylvia M. Miescher, Alexander Schaub, Marco Ghielmetti, Michael Baumann, Monique Vogel, Reinhard Bolli, and Beda Stadler. 61. Treatment of Pemphigus Vulgaris with Protein A Immunoadsorption: Case Report of Long-Term History Showing Favorable Outcome: Nina Frost, Gerald Messer, Gerhard Fierlbeck, Teut Risler, and Simon D. Lytton. 62. Immunosuppressive Therapy and Clinical Evolution in Forty-nine Patients with Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis: E Kokolina, E Alexopoulos, C Dimitriadis, A Vainas, P Giamalis, A Papagianni, D Ekonomidou, and D Memmos. 63. Management of Thrombosis in Antiphospholipid Syndrome and Systemic Lupus Erythematosus in Pregnancy: Guillermo Ruiz-Irastorza and Munther A. Khamashta. 64. Gene-Gun Biolistic Immunization Encoding Glutamic Acid Decarboxylase: A Model for Studying Langerhans Cell Abnormalities and Mimicry in the Nonobese Diabetic Mouse: Béatrice Joussemet, Anh-Tuan Vu, Pierre Sai, and Jean-Marie Bach. 65. Intra-bone Marrow-Bone Marrow Transplantation: A New Strategy for Treatment of Stem Cell Disorders: Susumu Ikehara. 66. Removal of Pathogenic Autoantibodies by Immunoadsorption: Alon Y. Hershko and Yaakov Naparstek. 67. Chemokine Receptors: Attractive Targets for Drug Discovery: Nuria Godessart. 68. Rationale for T Cell Inhibition by Cyclosporin A in Major Autoimmune Diseases: G F Ferraccioli, P Tomietto, and M De Santis. 69. Partial Response to Anti-CD20 Monoclonal Antibody Treatment of Severe Immune Thrombocytopenic Purpura in a Patient with Common Variable Immunodeficiency: J Carbone, A Escudero, M Mayayo, M Ballesteros, A Perez-Corral, S Sanchez-Ramon, E Sarmiento, D Micheloud, and E Fernandez-Cruz. 70. CD20 Mimicry by a mAb Rituximab-Specific Linear Peptide: A Potential Tool for Active Immunotherapy of Autoimmune Diseases: Federico Perosa, Elvira Favoino, Maria Antonietta Caragnano, and Franco Dammacco. 71. Anticytokine Therapy, Especially Anti-Interferon-, as a Pathogenetic Treatment in TH-1 Autoimmune Diseases: Simon Skurkovich and Boris Skurkovich. 72. Therapeutic T Cell-Based Vaccination for Neurodegenerative Disorders: The Role of CD4+CD25+ Regulatory T Cells: Michal Schwartz and Jonathan Kipnis. 73. Tumor Necrosis Factor Inhibitor Therapy for Rheumatoid Arthritis: Stanley M. Naguwa. 74. Pathogenesis of Rheumatoid Arthritis: Targeting Cytokines: Jochen Zwerina, Kurt Redlich, Georg Schett, and Josef S. Smolen. 75. Anti-inflammatory and Immune Regulatory Properties of 5-androsten-3ß, 17ß-Diol (HE2100), and Synthetic Analogue HE3204: Implications for Treatment of Autoimmune Diseases: D Auci, F Nicoletti, K Mangano, R Pieters, S Nierkens, L Morgan, H Offner, J Frincke, and C Reading. 76. Immunomodulatory Effects of Intravenous Immunoglobulins as a Treatment for Autoimmune Diseases, Cancer, and Recurrent Pregnancy Loss: Tal Sapir, Miri Blank, and Yehuda Shoenfeld. 77. Response of Vasculitic Peripheral Neuropathy to Intravenous Immunoglobulin: Yair Levy, Yosef Uziel, Giesele Zandman, Pnina Rotman, Hawared Amital, Yaniv Sherer, Pnina Langevitz, Boleck Goldman, and Yehuda Shoenfeld. 78. Involvement of Innate Immunity in the Development of Inflammatory and Autoimmune Diseases: Helena Tlaskalová-Hogenová, Ludmila Tucková, Renata Stepánková, Tomás Hudcovic, Lenka Palová-Jelínková, Hana Kozáková, Pavel Rossmann, Daniel Sanchez, Jana Cinová, Tomás Hrncír, Miloslav Kverka, Lenka Frolová, Holm Uhlig, Fiona Powrie, and Paul Bland. 79. Do We Need New Treatment That Goes beyond Tumor Necrosis Factor Blockers for Rheumatoid Arthritis?: Reinhard E. Voll and Joachim R. Kalden