Lupus—molecular and cellular pathogenesis.

Abstract

Leading basic and clinical investigators from around the world summarize the most recent research on the molecular and cellular origins of lupus. Their cutting-edge articles review the mechanisms underlying abnormal immunity and introduce the powerful new concept that a disorder of multiple genes underlies the abnormal immune response, leading directly to the development of lupus. This pathophysiology is shown to involve a wide variety of cell types, including T cells, B cells, natural killer cells, macrophages/monocytes, and endothelial cells. Over time, the resulting long-term inflammation causes irreversible cell destruction and, ultimately, organ failure. Lupus: Molecular and Cellular Pathogenesis is a masterful new synthesis of all the new knowledge emerging today about lupus. Its new perspectives will sharpen the focus of research and ultimately lead to better and more effective treatment. 1 Lupus: The Clinical Entity -- 2 The Vascular Endothelium: A New Actor in The Pathogenesis of Vascular Injury in Systemic Lupus Erythematosus -- 3 Nitric Oxide in Systemic Lupus Erythematosus: Implications for Immunity and Inflammation -- 4 Molecular Mimicry, Altered Apoptosis, and Immunomodulation as Mechanisms of Viral Pathogenesis in Systemic Lupus Erythematosus -- 5 Clustering and Proteolytic Cleavage of Autoantigens in Surface Blebs of Apoptotic Cells: Implications for Pathogenesis of SLE -- 6 Immune Effects of Bacterial DNA and Their Possible Role in the Pathogenesis of Lupus -- 7 Genetics of Systemic Lupus Erythematosus -- 8 Genetic Insights into Murine Lupus -- 9 Murine Graft-vs-Host Disease: Relevance to Human Lupus Immunopathogenesis and Therapy -- 10 Lessons From Knockout and Transgenic Lupus-Prone Mice -- 11 B Cells in Systemic Lupus Erythematosus -- 12 Mechanisms of the Pathogenic Autoimmune Response in Lupus: From Mouse Models to Human Disease -- 13 T-Cell Autoimmunity in Lupus: Ignorance, Anergy, and Activation -- 14 T-, B-, and Natural Killer Cell Dysfunction in Murine Systemic Lupus Erythematosis Models -- 15 Mechanisms of T Helper Cell Activation and Function in Systemic Lupus Erythematosus -- 16 A Genetic Mechanism Underlying Deficient Type I Protein Kinase A Activity in Systemic Lupus Erythematosus T Lymphocytes -- 17 Impaired DNA Methylation in Lupus T Cells -- 18 Impaired Non -- Antigen-Specific T-Cell Cytolytic Activity in SLE -- 19 Natural Killer Cells and CD8+ T Cells in the Downregulation of Antibody Production in Healthy Subjects and SLE: A Role for Transforming Growth Factor-? and Interleukin-2 -- 20 Cytokines in the Immunopathogenesis of Lupus. -- 21 Cytokine Gene Expression in Human Systemic Lupus Erythematosus -- 22 Balance Between Type 1 and Type 2 Cytokine-Secreting Cells: Impact on Disease Activity in Systemic Lupus Erythematosus -- 23 Autoantibodies as a Source of Peptides That Regulate Autoantibody Production -- 24 Autoantibodies to Intracellular Antigens in Systemic Lupus Erythematosus Patients That Bind and Penetrate Cells -- 25 Pathogenesis of Autoantibody Production and Glomerulonephritis in Pristane-Treated Mice: An Inducible Model of SLE -- 26 Anti-DNA Antibodies: Markers of the Pathogenesis of Systemic Lupus Erythematosus -- 27 The Anti-DNA Response in Lupus: Structure, Initiation, and Pathogenesis -- 28 Glomerular Binding Antibodies in Systemic Lupus Erythematosus -- 29 The Antiphospholipid Syndrome: Mechanisms of Autoantibody-Mediated Thrombosis -- 30 Autoimmune-Associated Congenital Heart Block: Bringing Bedside Challenges to the Bench -- 31 Role of Calreticulin Autoimmunity in the Pathogenesis of Photosensitive Cutaneous Lupus Erythematosus -- 32 Complement System and Systemic Lupus Erythematosus -- 33 Type One Complement Receptor and Human SLE -- 34 Fc? Receptor Polymorphisms: Insights into Pathogenesis -- 35 Immune Complexes and Autoantibodies to C1q -- 36 Lipids and Lupus: The Fats of the Matter -- 37 Immunosuppressive Agents: Biologic Effects In Vivo and In Vitro -- 38 Treatment of Systemic Lupus Erythematosus by Selective Inhibition of T-Cell Function -- 39 Targeting Costimulatory and Other Signaling Molecules in Murine Lupus -- 40 Management of Murine Lupus by Correction of Fas and Fas Ligand -- Induced Apoptosis: Therapeutic Rationale and Strategies.