The Rose and Mackay Textbook of Autoimmune Diseases, 7e (Aug 9, 2024)_(0443239460)_(Academic Press).pdf

The Rose and Mackay Textbook of Autoimmune Diseases Copyright Dedication Contents to Volume 1 prelims1-volume2.pdf Contents to Volume 2 List of contributors List of editors and section editors Editors Section editors Basic science Ear nose and throat Dermatology Endocrinology Hematology Hepatobiliary and gastroenterology Nephrology Neurology Ophthalmology Pulmonary Rheumatology Preface 1 Development of adaptive immune cells Self versus nonself Adaptive immune cell development Lymphocyte progenitors T cell development Altered mechanisms of T cell tolerance as promoters of autoimmunity B cell development Antibody diversity Self-reactive B cells are inherently part of the peripheral B cell pool Altered mechanisms of B cell tolerance and autoimmunity Conclusion Acknowledgment References 2 Revision to the origins of the mononuclear phagocyte Key points Overview Steady-state development of macrophages Transcriptional regulation of tissue-resident macrophages Common macrophage transcriptional profiles Adipose tissue macrophages Cardiac tissue macrophages Intestinal macrophages Kupffer cells Langerhans cells Peritoneal macrophages Lung macrophages Brain macrophages Nerve-associated macrophages Osteoclasts Splenic macrophages Synovial macrophages M1 and M2 paradigm revisited Future directions References 3 Tolerance and activation of peripheral B and T cells B cell central tolerance “checkpoints” in humans Tonic signaling at the immature B cell stage Receptor editing is likely a dominant tolerance mechanism at the immature B cell stage in mice and humans The special case of immature B cell deletion in response to DNA-protein complexes T cell activation, T-B collaboration, and peripheral B cell tolerance Self-reactive B cells at the transitional B cell stages are likely most susceptible to receptor downregulation and subseque... Late transitional and mature follicular B cells are anergized by selective downregulation of IgM, but anergic B cells are a... An overview of T cell tolerance and peripheral T cell activation The simultaneous generation of CD4+ T cell subsets and the induction of the extrafollicular response The transient extrafollicular induction of autoimmunity after infection likely reflects the major contribution of self-reac... The extrafollicular response, tolerance, and common autoimmune disorders Regulatory T cells in the maintenance of B cell tolerance Autoantibodies in common variable immunodeficiency likely reflect altered T effector/T reg ratios that allow anergic B cell... Germinal center B cell tolerance may reflect a default process and a break in tolerance at this location may lead to frank ... Conclusion Acknowledgments References 4 Genetic alterations leading to autoimmunity Introduction The genetics of autoimmunity before development of the genome-wide association study Evidence supporting the role of genetics in autoimmune diseases Linkage studies in autoimmune diseases Candidate gene studies identify the first non-HLA associated autoimmune disease risk genes The genome-wide association study Genome-wide association study discover a trove of autoimmune disease associations Fine mapping autoimmune disease loci with the Immunochip Moving from genetic association to functional mechanism in the post-GWAS era The next technology advance: single cell sequencing Leveraging polygenic risk scores to predict disease Summary References 5 Microbiome in autoimmunity Introduction Alterations in the gut microbiome in autoimmune diseases Inflammatory bowel diseases Type 1 diabetes Multiple sclerosis Rheumatoid arthritis Systemic lupus erythematosus Mechanisms Metabolites Molecules mimicry Microbiota translocation Interventions Diet and metabolites Fecal microbiota transplantation Inflammatory bowel diseases Type 1 diabetes Multiple sclerosis Rheumatoid arthritis Systemic lupus erythematosus Conclusion References 6 Metabolic control of pathogenesis in autoimmune diseases Short summary Introduction Systemic lupus erythematosus Mitochondrial oxidative stress underlies mTOR activation in SLE Rheumatoid arthritis Autoimmune spondyloarthritis Scleroderma and systemic sclerosis Metabolic control of organ-specific autoimmune diseases Conclusions Acknowledgments References 7 Triggers for autoimmunity Introduction Self-antigens that escape tolerance Neoantigens Breaking tolerance to existing autoantigens Enhanced presentation of posttranslationally modified epitopes Cryptic epitopes Sequestered antigens Environmental triggers of autoimmunity Viral-induced autoimmunity Epstein–Barr virus Enterovirus Hepatitis C virus Herpes simplex virus SARS-CoV-2 Drug-induced autoimmunity Drug-induced lupus Potential mechanisms of drug-induced lupus Cellular autoimmunity Neutrophil extracellular traps Immune checkpoint inhibitor-induced autoimmunity Potential mechanisms of immune checkpoint inhibitor-induced autoimmunity Cellular autoimmunity Humoral autoimmunity Cytokine production Conclusion References 8 Organ damage in autoimmune disease Introduction Initiation of tissue injury Antibody-mediated tissue injury Organ-specific diseases initiated by autoantibodies Autoantibodies of unknown function Antibodies directed at ubiquitous self-antigens B cells as organizers of local inflammation B cell-directed therapies T cell-mediated tissue injury T cells as inflammatory effector cells Antigen-specific T cells T cells as B cell helpers or regulatory cells T cell-directed therapies Innate immune mechanisms Macrophages Neutrophils Innate lymphoid cells Soluble inflammatory mediators Soluble mediators of resolution Chronic tissue injury Hypoxia Immune senescence Cell death Fibrosis Fibroblasts Pro-fibrotic and antifibrotic soluble mediators Targeting fibrosis Failed resolution Genetics of tissue injury Loss of function Implications for therapy References 9 Therapeutic strategies for treating autoimmune disease Immunosuppression versus targeted therapy B cell depletion T cell-directed therapy Cytokine blockade Small molecule immune inhibitors Immunoablation and reconstitution Antigen-specific therapy Conclusion References 10 Systemic lupus erythematosus Introduction History Disease diagnosis and classification Epidemiology, genetics, and the environment Pathogenesis Adaptive immunity Innate immunity Clinical features Clinical presentation Mucocutaneous manifestations Arthritis Renal involvement Neuro-psychiatric disease Hematologic manifestations Pulmonary and cardiovascular manifestations Other clinical manifestations Infections Clinical laboratory findings Treatment Outcome measures General therapeutic schema Therapeutic agents Antimalarials Corticosteroids Biologics Immunosuppressive medications Calcineurin inhibitors Cyclophosphamide Supportive treatments Future directions References 11 Systemic sclerosis (scleroderma) Definition and classification Epidemiology and etiology Sex bias, ethnic background and mortality trends Environmental factors Pathogenesis Genetic associations Preclinical disease models Microvascular disease in systemic sclerosis Inflammation and autoimmunity Cellular immunity Humoral autoimmunity Fibrosis Pathology Skin Lungs Gastrointestinal tract Kidneys Heart Pathology in other organs Clinical features Overview TABLE 11.5 Clinically significant organ involvement in systemic sclerosis. Initial clinical presentation Organ involvement Raynaud’s phenomenon Skin features Pulmonary features Interstitial lung disease Gastrointestinal involvement TABLE 11.6 Systemic sclerosis related autoantibodies and their demographic and clinical correlates. Renal involvement: scleroderma renal crisis Cardiac involvement It can be outcomes may be affected detecting preclinicalheart involvement in SSc Musculoskeletal complications Less recognized disease manifestations Biomarkers and autoantibodies in systemic sclerosis Screening and follow-up evaluation Management of patients with systemic sclerosis General principles Disease-modifying immunomodulatory therapy Immunosuppressive agents glucocorticoids cyclosporine, azathioprine, plaquenil,thalidomide, and rapamycin cyclophosphamide Mycophenolate mofetil Tocilizumab Extracorporeal photochemotherapy (photopheresis) cellulartherapies Therapy targeting fibrosis in patients with idiopathic pulmonary fibrosis Vascular therapy The goal of vascular therapy is to Raynaud’s ACE inhibitors Angiotensin II receptor blockers Patients unresponsive tothese therapies may require in severe cases adjunctiveagents Patients with nonhealing ischemic digitalulcerations may respond to statins and antioxidants often used for atrial arrhythmias for improving myocardial perfusionand left ventricular systolic function Treatment of gastrointestinal complications Gastroesophagealreflux Patientsshould be instructed to Prokinetic agents Surgical antireflux procedures Recurrent episodic bleeding from GAVE Treatment of interstitial lung disease Management of renal crisis Treatment of pulmonary arterial hypertension Natural history and prognosis References 12 Antiphospholipid syndrome Historical perspective Geoepidemiology Pathogenesis Double-hit model Thrombosis Activation of endothelial cells, platelets and immune cells Complement activation Resistance to activated protein C Pregnancy complications Proliferation and migration of trophoblasts Inflammation Complement activation Genetics Diagnosis, screening, and prevention Antiphospholipid antibody assays Lupus anticoagulant Antibodies against β2GPI and anticardiolipin antibodies Antibody profile Noncriteria antiphospholipid antibodies Clinical manifestations Thrombosis Obstetrical morbidity Neurological manifestations Cardiac manifestations Thrombocytopenia Pulmonary manifestations Skin manifestations Renal involvement Catastrophic antiphospholipid syndrome Management Primary thromboprophylaxis Prevention of recurrent thrombosis Alternative therapies for refractory and difficult cases Other therapies Pregnancy Recurrent early miscarriage Fetal death Management of pregnancy in patients with antiphospholipid syndrome and previous thrombosis Management of refractory obstetric antiphospholipid syndrome Postpartum period Risk assessment in antiphospholipid syndrome Future directions References 13 Sjögren’s disease Historical perspectives Establishing classification criteria for the disease Epidemiology Clinical presentation Introduction Nonspecific manifestations Periepithelial manifestations Glandular Extraglandular Extraepithelial manifestations Skin Nervous system Kidney Vasculitis Lymphoma [117–119] Disease course and prognosis Pathophysiology of Sjögren’s syndrome The normal salivary gland (structure and function) Genetic and environmental factors predisposing to Sjögren’s syndrome development Genetic factors The X chromosome Major histocompatibility complex genes and nonmajor histocompatibility complex genes Epigenetic modifications Environmental factors Biological factors Infections and vaccinations Organic chemical factors (smoking, alcohol, organic solvents) Hormonal factors Sex hormones Stress hormones and the growth hormone-insulin-like growth factor 1 axis Autoimmune epithelitis Initiation of the disease Autoantibodies Epithelial activation and immune sensing Establishment and perpetuation of the disease Cytokine—chemokine release Antigen presentation Immune cell activation and infiltration T cells B cells Macrophages Dendritic cells—plasmacytoid dendritic cells Natural killer cells Autoantigen fueling Mechanisms of tissue injury Periepithelial lesions Extraepithelial injury Lymphomagenesis The use of mouse models in the study of Sjögren’s syndrome Diagnosis and management Diagnosis Imaging modalities for evaluation of salivary glands Salivary gland ultrasonography Magnetic resonance imaging Autoantibodies related to Sjögren’s syndrome Minor labial salivary gland biopsy Differential diagnosis Management Nonpharmacologic interventions and preventive measures Local treatments Systemic and organ-based treatment Targeted treatments References 14 Rheumatoid arthritis Introduction Clinical, pathologic, and epidemiologic features Autoimmune features Genetic characteristics In vivo models Pathogenetic effector mechanisms Concluding remarks—future prospects References 15 Juvenile idiopathic arthritis Introduction Definition and classification Epidemiology Pathogenesis Genetic susceptibility Environmental factors Effector mechanism Clinical features Oligoarthritis Rheumatoid factor-positive polyarthritis Rheumatoid factor-negative polyarthritis Enthesitis-related arthritis Psoriatic arthritis Undifferentiated arthritis Systemic arthritis Macrophage activation syndrome Biomarkers Histopathology Morbidity/mortality Treatment Future directions References 16 Spondyloarthritis Introduction Disease history Definition of the disease and classification criteria Geoepidemiology Pathogenesis Genetics The role of HLA-B27 The role of non-MHC genes in spondyloarthritis Spondyloarthritis: an autoimmune or an autoinflammatory disease? Animal models Clinical features and treatment Clinical manifestations and the diagnostic approach Biomarkers Pathology with histology Morbidity/mortality Treatment References 17 Autoimmune myositis Defining autoimmune myositis Clinical and pathological descriptions of different phenotypes, including immune-mediated necrotizing myopathy Characteristic pathology, but significant overlap between phenotypes Epidemiological clues into mechanism Specific autoantibodies are strongly associated with phenotype, making them useful probes of disease mechanism Myositis-specific autoantibodies HMGCR autoantibodies in statin-associated immune-mediated necrotizing myopathy Mechanisms of disease The association of malignancy with autoimmunity: insights into disease initiation Enhanced expression of myositis autoantigens in regenerating muscle cells to focus propagation on muscle Modification of autoantigen expression or structure by immune effector pathways to generate a self-sustaining phenotype Therapeutic insights Concluding remarks References 18 Relapsing polychondritis Introduction Historical note Epidemiology Genetics and pathogenesis Clinical features and diagnosis Systemic manifestations Clinical evaluation Ear and nose manifestations Laryngotracheal and pulmonary manifestations Musculoskeletal manifestations Ocular manifestations Cutaneous manifestations Renal involvement Cardiovascular manifestations Neurological manifestations Association with other diseases Laboratory findings Imaging Differential diagnosis Assessment of disease activity and damage Treatment Nonsteroidal anti-inflammatory agents, colchicine and dapsone Corticosteroids Second-line therapies Biologic agents Surgical intervention Prognostic factors Summary References 19 IgG4-related disease Introduction Historical aspects Epidemiology Pathology Histological features Immunostaining Pathophysiology B cells T cells Serum IgG4 concentrations Autoimmune features Does the immunoglobulin G4 molecule participate in autoimmunity? Evidence for autoimmunity in immunoglobulin G4-related disease Galectin-3 Genetics An animal model Clinical features and disease associations Lymphadenopathy Lacrimal and salivary glands Orbits Ear/nose/throat Pancreas Immunoglobulin G4-related sclerosing cholangitis and cholecystitis Lung Kidney Thoracic aorta and coronary lesions Chronic periaortitis and retroperitoneal fibrosis Nervous system Other immunoglobulin G4-related disease lesions Classification criteria Treatment B cell-targeted treatments Costimulatory blockade CD4+ cytotoxic T lymphocytes Perspectives References 20 Necrotizing arteritis and small-vessel vasculitis Introduction Historical background Necrotizing arteritis Purpura and small-vessel vasculitis Polyarteritis nodosa Definition Epidemiology Clinical features Pathological features Clinical features and disease association Pathogenesis Environmental influences and genetic features Autoimmune features Animal models Diagnostic procedures Treatment Kawasaki’s disease Epidemiology Clinical features and disease associations Pathological features Pathogenesis Genetic features and environmental influences Autoimmune features Animal models Diagnostic procedures Treatment Anti-neutrophil cytoplasmic autoantibody vasculitis Definition Epidemiology Clinical features and disease associations Pathological features Pathogenesis Genetic features and environmental influences Autoimmune features Immunological non-responsiveness Animal models Diagnostic procedures Treatment Cryoglobulinemic vasculitis Definition Epidemiology Clinical features and disease associations Pathological features Pathogenesis Genetic features and environmental influences Autoimmune features Animal models Diagnostic procedures Treatment IgA Vasculitis (Henoch-Schonlein purpura) Definition Epidemiology Clinical features and disease associations Pathological features Pathogenesis Genetic features and environmental influences Autoimmune features Animal models Diagnostic procedures Treatment Concluding remarks—future prospects References 21 Large and medium vessel vasculitides Vasculitides of large and medium-sized blood vessels Giant cell arteritis Historic background Clinical, pathologic, and epidemiologic features The vascular lesion Epidemiology Genetic features Pathogenic mechanisms T cells and antigen-presenting cells in giant cell arteritis Macrophages (M&e_2C77;) in giant cell arteritis Neoangiogenesis of microvascular networks and intimal hyperplasia Immuno-stromal interactions in vasculitis Extravascular giant cell arteritis Treatment, monitoring, and outcome Takayasu arteritis Historic background Clinical, pathologic, and epidemiologic features Genetic predisposition Pathogenic mechanisms Treatment and outcome Concluding remarks – future perspectives Acknowledgment References 22 Autoimmune diseases of the kidney Introduction Historical perspective Definition of disease Nephrotic syndrome Minimal change disease Membranous nephropathy Focal segmental glomerulosclerosis Nephritic syndrome IgA nephropathy Rapidly progressive glomerulonephritis (RPGN) Lupus nephritis (covered extensively in chapter 10) Overlap nephrotic/nephritic syndrome Membranoproliferative glomerulonephritis (MPGN) Complement-mediated membranoproliferative glomerulonephritis (C-MPGN); complement factor 3 glomerulopathy (C3G) Immunoglobulin-mediated membranoproliferative glomerulonephritis (Ig-MPGN) Tubulointerstitial disease Geoepidemiology Pathogenesis Clinical features, disease associations, treatment, and outcomes Minimal change disease (MCD) Membranous nephropathy (MN) Focal segmental glomerulosclerosis (FSGS) IgA nephropathy (IgAN) Rapidly progressive glomerulonephritis (RPGN) Complement factor 3 glomerulopathy (C3G) Tubulointerstitial nephritis (TIN) Summary References 23 Autoimmune hemolytic anemia Introduction Historical background Classification Diagnostic pathway Warm-antibody autoimmune hemolytic anemia Primary and secondary warm-antibody autoimmune hemolytic anemia Epidemiology Pathogenesis Underlying or associated disorders Clinical features Therapy Drug-induced immune hemolytic anemia Cold-antibody autoimmune hemolytic anemia Cold agglutinin disease Epidemiology Pathogenesis Clinical features Diagnosis Therapy Secondary cold agglutinin syndrome Paroxysmal cold hemoglobinuria Atypical autoimmune hemolytic anemia Mixed warm and cold-antibody autoimmune hemolytic anemia Direct antiglobulin test-negative autoimmune hemolytic anemia Autoimmune hemolytic anemia in pregnancy Supportive therapeutic measures Transfusion Plasma exchange Vitamin and iron supplementation Thrombosis prophylaxis Measures against adverse effects of corticosteroids The future References 24 Acquired aplastic anemia Introduction Disease history Definition and classification Epidemiology Pathogenesis The immune pathogenesis of acquired aplastic anemia Triggers and predisposing factors for acquired aplastic anemia Genetic associations Medications and toxins Immunizations Association of acquired aplastic anemia with other disorders Potential role of telomere dysfunction Clinical manifestations Natural history & prognosis Clonal evolution in acquired aplastic anemia Diagnostic evaluation Treatment Supportive care Allogeneic hematopoietic stem cell transplant Patient selection Donor choice Graft choice Conditioning regimen Nontransplant therapy Immunosuppressive therapy Eltrombopag Androgens Cyclophosphamide Salvage therapy Conclusions and future directions References 25 Autoimmune clotting dysfunction Introduction Prothrombotic disorders Autoimmune inhibitors to protein C and protein S Autoimmune inhibitors to protein Z Anticoagulant disorders Autoimmune inhibitors to fibrinogen (factor I) Autoimmune inhibitors to prothrombin (factor II) and thrombin Autoimmune inhibitors to factor V Autoimmune inhibitors to factor VII Autoimmune inhibitors to factor VIII Autoimmune inhibitors to factor IX Autoimmune inhibitors to factor X Autoimmune inhibitors to factor XI Autoimmune inhibitors to factor XII Autoimmune inhibitors to factor XIII Autoimmune inhibitors to Van Willebrand factor Autoimmune inhibitors to further proteins Conclusion and future aspects COVID-19 and hypercoagulability References 26 Immune thrombocytopenia Introduction Disease history Definition and classification Geoepidemiology Pathogenesis Genetics backgrounds Environmental factors Autoimmune mechanisms Animal models for disease phenotype development Treatment First-line therapy Glucocorticoids Intravenous immunoglobulin Anti-D therapy Second-line therapy Thrombopoietin receptor agonist Rituximab Splenectomy Other agents Future directions References 27 Thrombotic thrombocytopenic purpura Introduction Disease history Epidemiology Definition, classification, and terminology Pathogenesis Genetics Environment Mechanism of thrombotic thrombocytopenic purpura von Willebrand factor and ADAMTS13 Autoimmunity Other mechanisms Animal models Clinical and laboratory features Clinical manifestation Microangiopathic hemolytic anemia and thrombocytopenia Organ involvements Pathohistology Laboratory biomarkers ADAMTS13 activity levels Anti-ADAMTS13 antibody detection Emerging biomarkers Evaluation and diagnosis Initial evaluation Differential diagnosis Systemic disorders that induce microangiopathic hemolytic anemia and thrombocytopenia Other primary thrombotic microangiopathies Presumptive diagnosis Confirmed diagnosis Evaluation for organ injury Treatment for immune-mediated thrombotic thrombocytopenic purpura Therapeutic plasma exchange Immunosuppressive agents Glucocorticoids Rituximab Other immunosuppressive agents Therapies targeting von Willebrand factor Caplacizumab N-acetylcysteine Splenectomy Emerging therapies Therapy for congenital thrombotic thrombocytopenic purpura Special populations Thrombotic thrombocytopenic purpura during pregnancy Jehovah’s Witnesses Future directions Glossary References 28 Macrophage activation syndrome Introduction History of macrophage activation syndrome Definition and classification criteria for macrophage activation syndrome Geoepidemiology of macrophage activation syndrome Environmental factors and triggers Clinical features Natural history and mortality Biomarkers Pathology findings in macrophage activation syndrome Animal models Immunology and genetics Hormonal influences Treatment Future directions References 29 Autoimmune leukopenia Introduction Autoimmune neutropenia Epidemiology Pathophysiology Clinical features Diagnosis Management and treatment Conclusion and future directions Lymphopenia and antilymphocyte antibodies in autoimmune diseases References 30 Autoimmune thyroid diseases Introduction Chronic autoimmune thyroiditis Historic background Definition and classification Epidemiology Pathogenesis Autoimmune features Antigen presentation Autoantibodies T-cell responses Genetic factors Existential and environmental risk factors Sex Pregnancy Infections Stress Iodine Smoking and alcohol Vitamin D Selenium Drugs Microbiota In vivo models Pathologic effector mechanisms Clinical features Natural history Biomarkers Histopathology Morbidity and mortality Treatment Perspectives Graves’ disease Historic background Definition and classification Epidemiology Pathogenesis Autoimmune features Autoantibodies Immune mechanisms Genetic factors Existential and environmental risk factors Sex Pregnancy Infections Stress Iodine Vitamin D Smoking Radiation Immune-modulating drugs Microbiota In vivo models Pathologic effector mechanism Clinical features Natural history Biomarkers Histopathology Morbidity and mortality Treatment Graves’ orbitopathy and thyroid dermopathy Perspectives Acknowledgments Conflict of interest References 31 Autoimmune (Type 1) diabetes Introduction Epidemiology Asymptomatic islet autoimmunity Symptomatic autoimmune (type 1) diabetes Diagnostic criteria and classification of diabetes Etiology Genetic etiology of islet autoimmunity Environmental factors associated with first appearing autoantibodies Beta cell-related factors and islet autoimmunity Pathogenesis Pathophysiology Genetic factors Environmental factors Cellular mechanisms Humoral biomarkers Pathology Preclinical models of type 1 diabetes Primary prevention Secondary prevention Intervention Conclusions and future directions References 32 Adrenalitis Historical notes Anatomy and physiology of the adrenals Epidemiology of Addison’s disease and of autoimmune adrenalitis Autoimmune Addison’s disease (adrenalitis) Histopathology Animal models Induced immunity Spontaneous models Family history and genetic predisposition Cellular immunity Environmental factors Serological autoimmunity Adrenal cortex autoantibodies Steroid-producing cells autoantibodies Autoantigens recognized by adrenal cortex autoantibodies Techniques to detect 21-hydroxylase autoantibodies Autoantigens recognized by steroid-producing cells autoantibodies Techniques for determination of autoantibodies to other steroidogenic enzymes (17α-OHAbs and P450sccAbs) Other autoantibodies detected in patients with autoimmune Addison’s disease in the context of autoimmune polyglandular syndrome Pathogenesis Natural history of autoimmune Addison’s disease Diagnosis of autoimmune Addison’s disease Clinical manifestations General biochemical indices Hormonal tests Imaging Different clinical presentations of autoimmune Addison’s disease Association with other autoimmune disorders Therapy Conventional glucocorticoid therapy Conventional mineralocorticoid therapy Dehydroepiandrosterone therapy New therapies Regenerative therapy Steroid replacement during surgery, other illness, medical procedures, physical activity, and pregnancy Acute adrenal failure (adrenal crisis) Emergency Card Quality of life Autoimmune Addison’s disease and SARS-CoV-2 infection Mortality Osteoporosis Acknowledgments References 33 Autoimmune polyendocrine syndromes Historic background Autoimmune polyendocrine syndromes type1 (APS-1) Autoimmune polyendocrine syndrome type-2 Immumodys; regulation polyendocrinopathy enteropathy X-linked (IPEX) Autoantibodies in diagnosis of autoimmune polyendocrine syndromes Genetics of autoimmune polyendocrine syndromes Pathogenic mechanisms Concluding remarks – future prospects References 34 Autoimmune gastritis and pernicious anemia Introduction Epidemiology and clinical presentation Epidemiology Gastric atrophy, hypochlorhydria and clinical consequences Pernicious anemia Autoimmune gastritis Autoimmune comorbidities Genetic features Pathogenesis Experimental models Studies on humans Diagnosis Laboratory tests Endoscopy Histopathology Assessing the neoplastic risk Staging of atrophic gastritis and surveillance strategies of autoimmune gastritis patients Concluding remarks – future prospects References 35 Autoimmune hypophysitis Definition and classification Historical notes Epidemiology and body of literature Clinical features Primary hypophysitis Hypophysitis secondary to immune checkpoint inhibitors Pathological features Primary hypophysitis Hypophysitis secondary to immune checkpoint inhibitors Autoimmune features Genetic and environmental influences Animal models Primary hypophysitis Hypophysitis secondary to immune checkpoint inhibitors Diagnosis Primary hypophysitis Hypophysitis secondary to immune checkpoint inhibitors Treatment Primary hypophysitis Hypophysitis secondary to immune checkpoint inhibitors Outcome Primary hypophysitis Hypophysitis secondary to immune checkpoint inhibitors A comparison between primary hypophysitis and hypophysitis secondary to immune checkpoint inhibitors Concluding remarks – future perspectives References 36 Autoimmune primary ovarian insufficiency Introduction Ovarian autoimmunity and primary ovarian insufficiency Diagnosis of autoimmune primary ovarian insufficiency Treatment of primary ovarian insufficiency Conclusions References 37 Endometriosis as an autoimmune disease Introduction Disease history Disease definition and classification criteria Geoepidemiology Pathogenesis Genetics Hormonal influences The immunology of endometriosis Inflammatory pathways The role of immune cells in the pathogenesis of endometriosis Macrophages Uterine natural killer cells Mast cells Neutrophils Lymphocytes Humoral immune factors in endometriosis Cytokines and growth factors Complement Animal models Clinical features Natural history Biomarkers Pathology Peritoneal endometriosis Ovarian endometrioma Deep infiltrative endometriosis Diagnosis Nonsurgical approaches to the diagnosis of endometriosis Surgical approaches to the diagnosis of endometriosis Treatment Morbidity Future directions in endometriosis References 38 Primary hypoparathyroidism or non-surgical hypoparathyroidism Biological effect of parathyroid hormone Classification and etiopathology of non-surgical hypoparathyroidism Autoimmune hypoparathyroidism Nongenetically determined autoimmune hypoparathyroidism Significance of calcium sensing receptor and NACTH leucine-rich-r