Systemic lupus erythematosus (S.L.E.), commonly called lupus, is a chronic autoimmune disorder that can affect virtually any organ of the body. In lupus, the body's immune system, which normally functions to protect against foreign invaders, becomes hyperactive, forming antibodies that attack normal tissues and organs, including the skin, joints, kidneys, brain, heart, lungs, and blood. Lupus is characterized by periods of illness, called flares, and periods of wellness, or remission. Because its symptoms come and go and mimic those of other diseases, lupus is difficult to diagnose. There is no single laboratory test that can definitively prove that a person has the complex illness. To date, lupus has no known cause or cure. Early detection and treatment is the key to a better health outcome and can usually lessen the progression and severity of the disease. Anti-inflammatory drugs, anti-malarials, and steroids (such as cortisone and others) are often used to treat lupus. Cytotoxic chemotherapies, similar to those used in the treatment of cancer, are also used to suppress the immune system in lupus patients. A new edition of this established and well regarded reference which combines basic science with clinical science to provide a translational medicine model. Systemic Lupus Erythematosus is a useful reference for specialists in the diagnosis and management of patients with SLE, a tool for measurement of clinical activity for pharmaceutical development and basic research of the disease and a reference work for hospital libraries. - Highly illustrated and in full color throughout- Basic science section expanded to allow the reader to focus on the newest techniques in molecular medicine and its effects on disease expression and treatment- Clinical aspects and new drugs will be covered in great detail providing a useful reference to both experienced clinicians and physicians with an interest in lupus in their clinical practice
Front Cover
1
Systemic Lupus Erythematosus 4
Copyright 5
Dedication
6
Table of Contents 8
List of Contributors 10
Foreword 14
Preface 16
Introduction 18
PART I -
22
Chapter 1 Major Histocompatibility Complex Class II 24
The MHC region 24
HLA polymorphism 25
Extended linkage disequilibrium at the MHC 26
Conserved extended haplotypes/ancestral haplotypes 26
The sequence of the MHC 26
Nomenclature of HLA and non-HLA alleles 27
HLA class I molecules 27
HLA class II molecules 29
HLA-DRB gene haplotypes 29
The MHC region and SLE 30
SNP-based MHC analyses in SLE 32
The future: defining causal variation 37
References 37
Chapter 2 Genetic Susceptibility and Class III Complement Genes 42
Introduction 42
Fourth component of complementnbsp(C4) 44
C2 and factor B 53
C4 deficiency and gene copy number variation in SLE 53
C2 deficiency and susceptibility to SLE 57
Acquired C4 and/or C2 deficiency and susceptibility to systemic lupus erythematosus 58
Immune complex processing and the complement system 58
Targeted gene knockouts 59
Further speculation on the association between systemic lupus erythematosus and complement deficiency 60
Detection of complement deficiency, phenotypic and genotypic variations 61
References 61
Chapter 3 Constitutive Genes and Lupus 68
Introduction 68
Pathway 1: Clearance and processing of immune complexes 68
Pathway 2: Toll-like receptor/type I interferon signaling 71
Pathway 3: Immune signal transduction 74
Other loci associated with SLE 76
Conclusion 77
References 77
Chapter 4 Genetics of Lupus in Mice 84
Mouse models of lupus 84
Dissecting the genetics of lupus in mice 84
Predisposing loci and genes in spontaneous lupus mouse models 85
Systemic autoimmunity in normal background gene knockout/mutated and transgenic mice 91
Gene knockout and transgenic lupus background mice 104
Implications for human SLE 113
Conclusion 114
References 114
Chapter 5 B-Cell Tolerance and Autoimmunity 128
B-cell tolerance 128
Early B-cell development and central tolerance mechanisms 128
Peripheral tolerance in B-cells 131
Links between genetic susceptibility to lupus and defects in tolerance 132
References 133
Chapter 6 Dendritic Cells in SLE 136
Introduction 136
Human DC subsets 136
Dendritic cells and the control of peripheral tolerance 139
DCs in human autoimmune diseases 140
Conclusion 143
References 143
Chapter 7 T-Cells and Systemic Lupus Erythematosus 150
Introduction 150
Central tolerance 150
T-cell activation and signal transduction 151
Transcription factors and gene expression 152
CD4 helper T cells and cytokine production 154
T follicular helper cells 157
Regulatory T cells 157
CD8 T cells and cytotoxic responses 157
Double-negative T cells 158
Adhesion molecules 158
Concluding remarks 158
References 158
Chapter 8 B-Lymphocyte Biology in SLE 164
Introduction 164
Fundamental features of B-cell immune responses 164
B-cell tolerance and receptor editing 166
Toll-like receptor (TLR) control of B-cell activation in lupus 166
B cells in antigen presentation and epitope spreading in autoimmune responses 169
Unique antigen-presenting features of B cells 172
Co-stimulatory processes in B-cell immunity 173
BAFF/BLyS in SLE 174
Conclusion 177
References 178
Chapter 9 Polymorphonuclear and Endothelial Cells 184
Introduction 184
Profile of adiponectin in health and disease 186
mEPCR: Protection of the endothelium 186
The CD11b chain serves as a switch hitter of the CR3-dependent influence on the cell-mediated immune system 187
Endothelial dysfunction and progression of atherosclerosis and renal disease 189
Conclusion 193
References 193
Chapter 10 Mechanisms and Consequences of Mitochondrial Dysfunction and Oxidative Stress in T-Cells of Patients with SLE 198
Introduction 198
Redox control of T-cell signal processing 198
Mitochondrial checkpoints of cell death pathway selection: Deltapsim, ATP synthesis, ROI and NO production, Ca2+ fluxing an ... 199
Mechanisms of MHP and ATP depletion and predisposition to necrosis in lupus T cells 199
Increased necrosis promotes pro-inflammatory state in patients with SLE 200
Detection of the mitochondrial gene expression signature in lupus T cells 200
Association of non-conserved coding sequence polymorphisms innbspmitochondrial DNA with SLE 202
Activation of the mammalian target of rapamycin (mTOR) innbsplupus T cells 203
Mitochondrial checkpoints of Ca2+ fluxing 205
Targeting of mitochondrial checkpoints in T-cell activation for treatment of SLE 205
References 206
Chapter 11 Cell Cycle Regulation and Systemic Lupus Erythematosus 212
The cell cycle machinery and its association with T-cell function 212
From T-cell exposure to antigen to loss of tolerance 213
T-cell cycling regulation and tolerance: The p21- and p27-deficient mouse models 215
The role of cell cycle regulation in autoimmunity development 216
Perspectives: Possible effect of cell cycle control in autoimmune disease treatment 217
References 217
Chapter 12 The Role of Reactive Nitrogen and Oxygen Intermediates in Systemic Lupus Erythematosus 220
Introduction 220
Biology of reactive intermediates 220
Nitric oxide biology in murine models of lupus 225
Reactive intermediates in human lupus 227
Conclusion 228
Acknowledgements 228
References 229
Chapter 13 Origins of Antinuclear Antibodies 234
Introduction 234
Diagnostic importance of ANAs 235
Structure of lupus autoantigens and implications for autoantibody production 236
Nucleic acid components of lupus autoantigens stimulate type I interferon production 238
Autoimmunity in mice with defects in the degradation of or response to nucleic acids 240
Role of T cells in autoantibody production (see also Chapter 7) 242
Role of B lymphocytes and plasma cells in autoantibody production (see also Chapter 8) 245
Future directions 250
References 250
Chapter 14 Anti-DNA Antibodies: Structure, Regulation and Pathogenicity 256
Normal immunology of antibodies and B cells 256
Anti-DNA antibodies origins, structure, idiotypes, antigenic cross-reactivity and pathogenicity
Regulation of anti-dsDNA B cells 268
Anti-DNA antibody transgenic mice 268
Genes that regulate B-cell tolerance 269
Detection of anti-DNA antibodies 270
Therapy 271
Summary 272
References 273
Chapter 15 Extractable Nuclear Antigens and SLE: Specificity and Role in Disease Pathogenesis 280
Introduction 280
Autoantigen specificity 280
Specific assays for the detection of autoantibodies to Ro, La, RNP, and Sm 284
Generation of autoantibodies 285
Pathophysiology of anti-ENA antibodies - roles in SLE 287
Conclusions 290
References 290
Chapter 16 Antihistone and Antispliceosomal Antibodies 296
Origin of antihistone antibodies 296
Histones are key protein component of cellular chromatin 296
Assays for antihistone antibodies 297
Prevalence and disease association of antihistone and antinucleosome antibodies 298
Antihistone in systemic lupus erythematosus 299
Antihistone in drug-induced lupus 300
Antispliceosomal antibodies 300
Cellular localization and function of snRNP 300
Reactivity of anti-snRNPs autoantibodies 301
History of detection of autoantibodies to snRNPs and potential problems 303
Detection of antibodies to snRNPs in clinical practice 304
Clinical significance of antibodies to snRNPs 305
Immunologic characteristics of anti-U1RNP and Sm antibodies 307
Problems and confusions in anti-snRNPs antibody testing 307
Mechanism of production 308
References 309
Chapter 17 Toll-Like Receptors in SLE 314
Introduction 314
Toll-like receptor family 314
TLR2 and its TLR co-receptor partners TLR1, TLR6, and TLR10 315
TLR3 317
TLR4 317
TLR5 318
TLR7 319
TLR8 321
TLR9 322
RP105 323
Conclusions 324
References 324
Chapter 18 Interferon-Alpha in Systemic Lupus Erythematosus 328
Introduction 328
Type I IFNs in immune responses 328
IFN in SLE 330
Summary: A model for type I IFN expression and its pathogenic role in SLE 336
References 337
Chapter 19 Immune Complexes in Systemic Lupus Erythematosus 342
Introduction 342
Characteristics of immune complexes 342
Biologic properties of immune complexes 345
Tissue deposition of immune complexes 350
Measurement of immune complexes and the use of these tests in patients with SLE 354
Development of therapies based on the immune complex model 355
References 355
Chapter 20 Complement and Tissue Injury in SLE 360
HISTORICAL OVERVIEW 360
BIOLOGY OF THE COMPLEMENT SYSTEM 361
COMPLEMENT AND INFLAMMATION 365
COMPLEMENT AND SLE 366
COMPLEMENT DEFICIENCY AND SLE (AND OTHER DISEASES) 368
COMPLEMENT AS BIOMARKERS FOR SLE DIAGNOSIS AND MONITORING 374
ANTICOMPLEMENT THERAPEUTICS FOR SLE 377
ACKNOWLEDGEMENTS 378
References 378
Chapter 21 Humoral Pathogenesis 386
INTRODUCTION 386
FCgRS: STRUCTURE AND FUNCTIONS 386
ROLES OF FCgR IN SLE 391
FCgR TARGETED TREATMENTS 397
FUTURE DIRECTIONS 398
References 398
Chapter 22 Drug-Induced Lupus Mechanisms 406
Introduction 406
STRUCTURES OF DRUGS CAUSING DRUG-INDUCED LUPUS 406
ANTIDRUG ANTIBODIES 406
DRUG-DNA INTERACTIONS 407
DRUG-HISTONE INTERACTIONS AND ANTIHISTONE ANTIBODIES 408
ABNORMAL IMMUNE REGULATION 408
GENETIC FACTORS 409
NEUTROPHIL-MEDIATED OXIDATIVE METABOLISM 411
EPIGENETIC MECHANISMS 412
ANIMAL MODELS 415
XENOBIOTICS 417
CONCLUSIONS 419
References 420
Chapter 23 Gender and Age in Lupus 426
Late-onset systemic lupus erythematosus 426
Gender and SLE 428
Human disease 429
Summary 438
References 438
Chapter 24 Roles for Infections in Systemic Lupus Erythematosus Pathogenesis 446
Introduction 446
Infection and SLE initation 446
Infections exacerbating SLE disease 450
Summary 453
References 453
Chapter 25 Systemic Lupus Erythematosus in Domestic Animals 458
Introduction 458
Canine systemic lupus erythematosus 458
Feline systemic lupus erythematosus 467
Equine systemic lupus erythematosus 468
References 469
Chapter 26 Pathogenesis of Lupus Nephritis 474
The pathogenesis of lupus nephritis 474
Tools for studying lupus nephritis pathogenesis 474
Role of anti-dna antibodies andnbspimmune complexes innbsplupusnbspnephritis 476
The role of nucleosomes innbsplupusnbspnephritis 477
Role of lymphocytes in lupus nephritis 478
Role of myeloid cells in lupus nephritis 480
Conclusion 485
References 485
Chapter 27 Tissue Injury and the Skin 496
Introduction 496
Conclusion 506
References 506
Chapter 28 Neuropsychiatric Systemic Lupus Erythematosus: Mechanisms of Injury 512
Introduction 512
Vascular Pathology 512
Blood-brain barrier 514
Central nervous system 516
Peripheral and autonomic disease 519
Clinical studies of pathogenesis 520
Conclusion 525
References 525
Chapter 29 Atherosclerosis and Tissue Injury in Systemic Lupus Erythematosus 534
Introduction 534
Recognition of increased coronary heart disease risk in SLE 534
Noninvasive measures of atherosclerosis to predict chd outcomes in SLE 536
The relationship between traditional cardiovascular risk factors and increased chd in SLE 536
Mechanisms involved in the expression of atherosclerosis in SLE 537
Summary 540
References 540
PART II -
544
Chapter 30 The Clinical Presentation of Systemic Lupus Erythematosus 546
Introduction 546
General symptoms 546
Criteria for lupus 547
General considerations regarding lupus 548
Musculoskeletal system 550
Clinical involvement of the renal system 551
Clinical involvement of the central nervous system 552
Clinical presentation of cardiovascular lupus 553
Pulmonary disease and lupus 554
Hematology of sle 554
Clinical presentation of lupus of the skin 555
Gastrointestinal tract and liver disease in sle 555
The eye and sle 556
Miscellaneous organ involvement 556
References 556
Chapter 31 Neonatal Lupus 562
Introduction 562
Passively acquired CHB: an irreversible manifestation of NL when complete block 563
The transient skin rash 566
Less commonly encountered manifestations of NL 566
Candidate antigen-antibody systems in NL 568
Proposed mechanisms of immune injury 571
Genetics of the NL child and the mother 575
Maternal disease at identification of neonatal lupus and progression 577
Treatment and prevention of cardiac NL 578
Conclusions 585
References 585
Chapter 32 SLE in Children 594
Introduction 594
Presentation at diagnosis with cSLE 594
Mucocutaneous Manifestations 595
Raynaud Phenomenon 596
Musculoskeletal Manifestations 596
Hematologic Manifestations 597
Neuropsychiatric Manifestations 598
Lupus Nephritis 599
Cardiovascular Manifestations 601
Endocrine Manifestations 602
Gastrointestinal Manifestations 603
Pulmonary Manifestations 603
Immunological Markers 604
Genetics 604
Overlap with Other Autoimmune Disease 605
Antiphospholipid Antibody Syndrome 605
SjOgren Syndrome 606
Special Therapeutic Considerations 606
Adherence 608
Outcome Measures 608
Cost of Care 608
Prognosis and Outcomes 609
Transition 609
Summary 610
References 610
Chapter 33 Drug-Induced Disease 620
Introduction 620
History 620
Definition 622
Prevalence 622
Demographic features 622
Clinical features 622
Laboratory findings 624
Diagnosis 625
Differential diagnosis 625
Therapy 626
Comments on certain drugs associated with drug-related lupus 626
Biological agents 634
Subacute cutaneous lupus erythematosus 640
Conclusion 641
References 641
Chapter 34 Laboratory Evaluation of Patients with Systemic Lupus Erythematosus 650
Introduction 650
Antinuclear antibodies 650
Nucleosome-specific antibodies 658
Antiphospholipid antibodies 661
Immunoglobulins 663
Immune complexes 663
Complement 663
Acute-phase reactants 664
Hematological abnormalities 665
Renal function 667
Synovial fluid 667
Pleural fluid 667
Pericardial fluid 668
Cerebrospinal fluid 668
References 668
Chapter 35 Pregnancy and Reproductive Concerns in Systemic Lupus Erythematosus 676
Introduction 676
Physiological changes relevant to women with underlying SLE 676
The immunology of implantation, pregnancy, and labor and delivery 677
The placenta 677
Management of pregnant women with SLE 678
Pharmacologic treatment of sle in pregnancy 684
Family planning and counseling 687
Sle and fertility 688
Contraception 688
Conclusion 688
References 688
Chapter 36 Epidemiology of Systemic Lupus Erythematosus 694
Introduction 694
Epidemiologic approaches in SLE 694
Morbidity from disease and/or treatment 704
Conclusions 709
References 710
Chapter 37 Monitoring Disease Activity 718
Measuring disease activity 718
Measuring flare 723
References 726
Chapter 38 Incomplete Lupus Erythematosus 728
Definition 728
Background 728
Epidemiology 730
Clinical presentation 730
Disease course in ILE 731
Pathogenesis 734
Summary 736
References 736
Chapter 39 Design of Clinical Trials for SLE 740
Reasonable regulatory requirements 740
Heterogeneity of the disease itself 741
References 746
CHAPTER 40 The Nervous System and Lupus 748
Introduction 748
Classification and frequency of NPSLE 748
Attribution of NPSLE: SLICC inception cohort study 749
Clinical impact and prognosis of NPSLE 750
Clinical manifestations 751
Pathogenesis of NPSLE 757
Diagnostic imaging and NPSLE 759
Diagnosis of NPSLE 760
Treatment of NPSLE 760
References 762
Chapter 41 Skin 768
Introduction 768
Overview 768
Subsets of Cutaneous Lupus Erythematosus 769
Lupus-Nonspecific Skin Lesions 778
Associated Skin Conditions 781
Lupus Criteria: Malar Rash, Photosensitivity, Oral Ulcers, and Discoid 781
Epidemiology/Natural History 782
Pathogenesis of Cutaneous Lupus Erythematosus 782
Measurement of Outcomes 783
Treatment 784
References 785
CHAPTER 42 Kidney 790
Introduction 790
Scope of lupus nephritis 790
Diagnosis of lupus nephritis 790
Kidney biopsy 795
Kidney pathology in SLE 797
The treatment of lupus nephritis 812
Renoprotective therapies 820
Patient follow-up for LN 821
Thrombotic microangiopathies that affect the kidney in SLE 823
Pregnancy and LN 825
Childhood lupus nephritis 825
Renal replacement therapies in SLE 826
Experimental therapeutics in SLE: the future of LN treatment 827
Conclusion 828
References 828
Chapter 43 Heart 836
Pericardial Disease 836
Myocardial Dysfunction 838
Conduction System 841
Valvular Heart Disease 842
Coronary Vasculitis 844
Coronary Atherosclerosis 845
Conclusion 849
References 849
Chapter 44 Vasculitis 854
The Spectrum of Vasculitis in Systemic Lupus Erythematosus 854
Differential Diagnosis of Sle Vasculitis 861
Management 861
Conclusion 861
References 862
CHAPTER 45 Lung 868
Introduction 868
Clinical assessment of sle-associated lung disease 868
Clinical assessment 869
Laboratory assessment 869
Thoracic imaging modalities 870
SLE-associated lung manifestations 873
Areas of debate 880
References 881
CHAPTER 46 Gastrointestinal: Liver 886
Introduction 886
Chronic active and lupoid hepatitis: early descriptions 887
Diagnostic criteria: sle and autoimmune hepatitis 887
Lupus and the liver: the vision of the clinician 889
Lupus and the liver: the vision of the histopathologist 891
Lupus and the liver: the vision of the serologist 892
Lupus and the liver: the vision of the immunogeneticist 899
Lupus and the liver: the vision of the epidemiologist 901
Conclusions 902
References 903
Chapter 47 Gastrointestinal: Nonhepatic 908
Oral cavity 908
Esophagus 911
Stomach and duodenum 912
Small and large intestine 913
Peritoneal cavity 917
Pancreas 918
Gallbladder 919
Spleen 919
Drug-related pathology 919
Conclusions 919
References 920
CHAPTER 48 Cellular Hematology 926
Introduction 926
Pathogenic mechanisms of cytopenias in SLE 926
Clinical manifestations and treatment of cytopenias in SLE 931
Anemia 932
Thrombocytopenia 934
Leukopenia 935
Bone marrow disease 935
Lymphoproliferative disease 936
References 936
CHAPTER 49 Musculoskeletal System: Articular Disease, Bone Metabolism 942
Arthritis 942
Tendon rupture 945
Myositis 945
Osteonecrosis 946
Osteoporosis 952
References 960
PART III -
964
CHAPTER 50 Antiphospholipid Syndrome: Pathogenesis 966
Historical background 966
Cell membrane phospholipids 967
Antiphospholipid antibodies 967
Pathogenesis of antiphospholipid antibodies 974
Cell receptors for antiphospholipid antibody interactions 977
Signaling pathways of cell activation 978
Antiphospholipid antibodies andnbspcomplement activation 978
References 979
CHAPTER 51 Endothelial Cell Damage and Atherosclerosis 988
Introduction 988
Evidence for an autoimmune etiology for atherosclerosis and vascular endothelial dysfunction in SLE 988
Inflammation and atherosclerosis: relevance to endothelial cells and SLE 990
Antiphospholipid syndrome, endothelial damage, and atherosclerosis 994
N
999
References 1000
CHAPTER 52 Laboratory Testing for Antiphospholipid Syndrome 1006
Introduction 1006
Historical perspective 1006
Lupus anticoagulant test 1007
Anticardiolipin antibody test 1009
Anti-beta2-Glycoprotein I assay 1011
Association of laboratory tests with aps clinical phenotype 1012
Conclusion 1016
References 1016
Chapter 53 Clinical Presentation of Antiphospholipid Syndrome 1022
Diagnostic approach to antiphospholipid syndrome 1022
Epidemiology 1023
Clinical features 1023
References 1031
CHAPTER 54 Pregnancy and Antiphospholipid Syndrome 1036
Introduction 1036
Mechanism of antiphospholipid syndrome-related obstetric disease 1036
Diagnostic approach to antiphospholipid syndrome 1038
Potential complications of antiphospholipid syndrome in pregnancy 1039
Therapeutic approach to antiphospholipid syndrome in pregnancy 1040
Obstetric management in the patient with antiphospholipid syndrome 1043
References 1044
Chapter 55 Treatment of Antiphospholipid Syndrome 1048
Introduction 1048
Primary thromboprophylaxis in patients with antiphospholipid antibodies 1048
Secondary thromboprophylaxis in patients with antiphospholipid syndrome 1050
Improving secondary thromboprophylaxis in patients with antiphospholipid syndrome 1052
Management of ``difficult'' cases 1053
Management of obstetric antiphospholipid syndrome 1054
Catastrophic antiphospholipid syndrome 1057
Future trends in the management of the antiphospholipid syndrome 1058
References 1059
PART IV -
1064
Chapter 56 Corticosteroid and Nonsteroidal Anti-Inflammatory Drug use in Systemic Lupus Erythematosus 1066
Biologic effects of glucocorticoids 1066
The effect of corticosteroids upon survival in SLE 1066
Indications for corticosteroids based on disease manifestations 1068
Patterns of corticosteroid therapy 1072
Prevention and treatment ofnbsplupus flares 1074
Steroid tapering 1075
Side effects of steroids 1076
Nonsteroidal anti-inflammatory drugs in SLE: uses and side effects 1077
References 1077
Chapter 57 Antimalarials and SLE 1082
Introduction 1082
Antimalarials and SLE 1082
Mechanism of action 1086
Toxicity 1087
Pregnancies and breast-feeding 1092
Contraindications 1093
Pharmacology, pharmacokinetic properties and blood HCQ dosage 1094
Drug interactions and cigarette smoking 1096
Dosage and follow-up 1097
Conclusion 1098
References 1098
Systemic Lupus Erythematosus: Cytotoxic Agents 1104
Introduction 1104
Azathioprine 1104
Cyclophosphamide 1107
Mycophenolate mofetil 1110
Calcineurin inhibitors 1114
Other agents 1116
Intravenous gamma globulin 1117
Cytotoxic therapy in SLE: the need for a strategy that best fits the patient 1118
General issues 1119
References 1125
Chapter 59 Biologic Agents in the Treatment of Systemic Lupus Erythematosus 1130
Cytokines 1130
Complement system 1133
Cell surface molecules 1133
Co-stimulatory molecules 1134
Intracellular targets 1135
Conclusion 1135
References 1135
Index 1140
List of Contributors
Joseph M. Ahearn, MD Lupus Center of Excellence, University of Pittsburgh Schools of the Health Sciences, Pittsburgh, PA, USA
Olga Amengual, MD, PhD Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Zahir Amoura, MD Service de Médecine, Interne 2 CHU Pitié-Salpêtrière, Paris, France
Cynthia Aranow, MD The Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute for Medical Research, North Shore–LIJ Health System, Manhasset, NY, USA
John P. Atkinson, MD Department of Medicine/Division of Rheumatology, Washington University School of Medicine, St. Louis, MO, USA
Tatsuya Atsumi, MD, PhD Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Ingrid Avalos, MD Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Dimitrios Balomenos, MD Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Cantoblanco, Spain
Jacques Banchereau, PhD Baylor Institute for Immunology Research, Dallas, TX, USA
George Bertsias, MD Department of Medicine, University of Crete School of Medicine, Heraklion, Greece
Markus Böhm, MD Department of Dermatology, University of Münster, Germany
Dimitrios T. Boumpas, MD, FACP Clinical Immunology and Allergy, University of Crete School of Medicine, Heraklion, Greece
D. Ware Branch, MD Department of Obstetrics and Gynecology H.A., University of Utah Health Sciences Center, Women and Newborns Clinical Program, Intermountain Healthcare, Salt Lake City, UT, USA
Hermine I. Brunner, MD, MSc, FAAP, FACR Lupus Center Scientific, Cincinnati Children's Hospital Medical Center, Division of Rheumatology, Cincinnati, OH, USA
Jill P. Buyon, MD New York University Medical Center, Tisch Hospital, New York, NY, USA
Livia Casciola-Rosen, PhD Johns Hopkins University School of Medicine, Department of Medicine, Baltimore, MD, USA
Ricard Cervera, MD, PhD, FRCP Department of Autoimmune Diseases Hospital Clínic, Barcelona, Catalonia, Spain
George Chamilos, MD Department of Medicine, Infectious Diseases Unit, University of Crete School of Medicine, Heraklion, Greece
Edward K.L. Chan, PhD University of Florida Health Science Center, Gainesville, FL, USA
Robert M. Clancy, PhD New York University School of Medicine, New York, NY, USA
Christine A. Clark, PhD Mount Sinai Hospital, LifeQuest Centre for Reproductive Medicine, Toronto, ON, Canada
Nathalie Costedoat-Chalumeau, MD AP-HP, Service de Médecine Interne, Centre de référence national pour le Lupus et le syndrome des Antiphospholipides, Centre Hospitalier Universitaire Pitié-Salpêtrière, France
Maura Couto, MD Rheumatology Department, Coimbra University Hospital, Praceta, Mota Pinto, Portugal
José C. Crispín, MD Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Mary K. Crow, MD Weill Cornell Medical College, Benjamin M. Rosen Chair in Autoimmunity and Inflammation Research, Hospital for Special Surgery, New York, NY, USA
Michael J. Day, BSc, BVMS(Hons), PhD, DSc, DiplECVP, FASM, FRCPath, FRCVS School of Veterinary Science, University of Bristol, Langford, UK
Betty Diamond, MD The Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute for Medical Research, North Shore–LIJ Health System, Manhasset, NY, USA
Iris Dotan, MD Department of Gastroenterology and Liver Diseases, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
Roland M. du Bois, MD National Jewish Health, Denver, CO, USA
Yong Du, MD, PhD Departments of Internal Medicine (Rheumatology), University of Texas, Southwestern Medical School, Dallas, TX, USA
Catia Duarte, MD Rheumatology Department, Coimbra Hospital University, Praceta, Mota Pinto, Portugal
Yun Deng, MD, MS Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Jan P. Dutz, MD Department of Dermatology and Skin Science, University of British Columbia, Vancouver, Canada
Olga Dvorkina, MD SUNY Downstate Medical Center, Brooklyn, New York, NY, USA
Thomas Ernandez, MD Vascular Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
Gerard Espinosa, MD, PhD Department of Autoimmune Diseases Hospital Clínic, Barcelona, Catalonia, Spain
A. Darise Farris, PhD Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
Michelle M.A. Fernando, MD Clinical Scientist, Faculty of Medicine, Section of Rheumatology, Imperial College London, London, UK
Barri J. Fessler, MD, MSPH Division of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, AL, USA
Aryeh Fischer, MD Division of Rheumatology and Interstitial Lung Disease Program, National Jewish Health, Denver, CO, USA
Deborah M. Friedman, MD, FAAP, FACC New York Medical College, NY, USA
Marvin J. Fritzler, PhD, MD Department of Medicine, University of Calgary, Alberta, Canada
Richard Furie, MD Albert Einstein College of Medicine, Division of Rheumatology and Allergy-Clinical Immunology, North Shore–Long Island Jewish Health System, Manhasset, NY, USA
Gary S. Gilkeson, MD Medical University of South Carolina, Ralph H. Johnson VAMC, Charleston, SC, USA
Ellen M. Ginzler, MD Department of Medicine, State University of New York Downstate Medical Center, Brooklyn, New York, NY, USA
John G. Hanly, MD Capital District Health Authority and Dalhousie University, Canada
Evelyn V. Hess, MD, MACP, MACR Division of Immunology and Allergy, Department of Internal Medicine, College of Medicine University of Cincinnati, OH, USA
Gary S. Hoffman, MD, MS Harold C. Schott Professor of Rheumatic and Immunologic Diseases, Center for Vasculitis Care and Research, Lerner College of Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA
Diane Horowitz,...
| Erscheint lt. Verlag | 29.10.2010 |
|---|---|
| Sprache | englisch |
| Themenwelt | Medizin / Pharmazie ► Medizinische Fachgebiete ► Orthopädie |
| Medizin / Pharmazie ► Medizinische Fachgebiete ► Pharmakologie / Pharmakotherapie | |
| Studium ► Querschnittsbereiche ► Infektiologie / Immunologie | |
| ISBN-10 | 0-08-096171-1 / 0080961711 |
| ISBN-13 | 978-0-08-096171-2 / 9780080961712 |
| Informationen gemäß Produktsicherheitsverordnung (GPSR) | |
| Haben Sie eine Frage zum Produkt? |
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Systemvoraussetzungen:
PC/Mac: Mit einem PC oder Mac können Sie dieses eBook lesen. Sie benötigen eine
eReader: Dieses eBook kann mit (fast) allen eBook-Readern gelesen werden. Mit dem amazon-Kindle ist es aber nicht kompatibel.
Smartphone/Tablet: Egal ob Apple oder Android, dieses eBook können Sie lesen. Sie benötigen eine
Geräteliste und zusätzliche Hinweise
Zusätzliches Feature: Online Lesen
Dieses eBook können Sie zusätzlich zum Download auch online im Webbrowser lesen.
Buying eBooks from abroad
For tax law reasons we can sell eBooks just within Germany and Switzerland. Regrettably we cannot fulfill eBook-orders from other countries.
EPUB (Adobe DRM)Größe: 53,7 MB
Kopierschutz: Adobe-DRM
Adobe-DRM ist ein Kopierschutz, der das eBook vor Mißbrauch schützen soll. Dabei wird das eBook bereits beim Download auf Ihre persönliche Adobe-ID autorisiert. Lesen können Sie das eBook dann nur auf den Geräten, welche ebenfalls auf Ihre Adobe-ID registriert sind.
Details zum Adobe-DRM
Dateiformat: EPUB (Electronic Publication)
EPUB ist ein offener Standard für eBooks und eignet sich besonders zur Darstellung von Belletristik und Sachbüchern. Der Fließtext wird dynamisch an die Display- und Schriftgröße angepasst. Auch für mobile Lesegeräte ist EPUB daher gut geeignet.
Systemvoraussetzungen:
PC/Mac: Mit einem PC oder Mac können Sie dieses eBook lesen. Sie benötigen eine
eReader: Dieses eBook kann mit (fast) allen eBook-Readern gelesen werden. Mit dem amazon-Kindle ist es aber nicht kompatibel.
Smartphone/Tablet: Egal ob Apple oder Android, dieses eBook können Sie lesen. Sie benötigen eine
Geräteliste und zusätzliche Hinweise
Zusätzliches Feature: Online Lesen
Dieses eBook können Sie zusätzlich zum Download auch online im Webbrowser lesen.
Buying eBooks from abroad
For tax law reasons we can sell eBooks just within Germany and Switzerland. Regrettably we cannot fulfill eBook-orders from other countries.
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