The Heart in Rheumatic, Autoimmune and Inflammatory Diseases

Pathophysiology, Clinical Aspects and Therapeutic Approaches

Udi Nussinovitch

• Publisher: Academic Press
• Year: 2017
• Print ISBN: 9780128032671
• eBook ISBN: 9780128032688
• Topic: Medicina
• Subtopic: Malattie e allergie

The prevalence of autoimmune diseases and rheumatic conditions is constantly increasing. Autoimmune diseases affect approximately 7-10% of the population of the United States, while more than 50, 000, 000 American adults suffer from some type of arthritis. The Heart in Rheumatic, Autoimmune and Inflammatory Diseases examines the complex mechanisms relating to cardiac diseases from a pathophysiological and clinical point of view. Autoimmune rheumatic diseases can affect the coronary vessels, myocardium, pericardium, heart valves and the conduction system. The diagnosis of these unique cardiac complications necessitates medical awareness and a high index of suspicion. Increased risk of advanced atherosclerosis plays a pivotal role in the development of cardiac diseases in systemic, rheumatic and autoimmune illnesses. Yet, other complex immune medicated mechanisms may contribute to the pathogenesis. Patients' optimal care requires coordination between the primary caregiver, the rheumatologist, immunologist and cardiologist. Screening for cardiovascular risk factors, recognition of high-risk patients and identification of subclinical cardiac conditions are of great importance. Moreover, regulation of inflammation, as well as abnormal immune responses and the initiation of early treatments should be the focus of patient management. A continuous attempt to identify novel therapeutic targets and change the natural history of the underlying disease and its cardiac manifestations is in progress. The book aims at providing the readers with a state of the art collection of up to date information regarding clinically important topics based on experts' perspectives.This book was a result of an extended coordinated collaboration of one-hundred and fifty-four distinguished scientists from thirty-one countries around the globe.- A review of common, as well as unusual (yet clinically significant) medical cardiac complications of prevalent rheumatic, autoimmune and inflammatory diseases.- Focuses on aspects of pathophysiological processes, clinical presentations, screening tests, prognostic implications and novel therapeutic approaches.- Presents an up-to-date "level of evidence and "strengths of recommendations for suggested therapies and reviews all randomized clinical trials, meta-analyses and other supporting published clinical findings.

Part I

Immune Medicated Cardiac Injury, Accelerated Atherosclerosis and the Study of Cardiac Involvements in Systemic Diseases

Outline

Chapter 1. Pathophysiology of Autoimmunity and Immune-Mediated Mechanisms in Cardiovascular Diseases

Chapter 2. Organ-Specific Autoimmune Myocardial Diseases: From Pathogenesis to Diagnosis and Management

Chapter 3. Autoantibodies Directed Against G-Protein-Coupled Receptors in Cardiovascular Diseases: Basics and Diagnostics

Chapter 4. Immune-Mediated Accelerated Atherosclerosis

Chapter 5. A Study of Cardiac Function, Atherosclerosis, and Arrhythmogenicity

Chapter 1

Pathophysiology of Autoimmunity and Immune-Mediated Mechanisms in Cardiovascular Diseases

O. Shamriz¹, U. Nussinovitch², and N.R. Rose^{3,4 1}Hadassah-Hebrew University Medical Center, Jerusalem, Israel ²Rambam Health Care Campus, Affiliated With the Technion Institute of Technology, Haifa, Israel ³Johns Hopkins University, Baltimore, MD, United States ⁴Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States

Abstract

Autoimmune diseases are known to have a number of effector mechanisms including environmental, genetic, hormonal, infectious, and psychological effectors. Studies have reported that various triggers and insults promote autoimmune responses or modulate the clinical course of autoimmune illnesses. A variety of cellular and molecular responses mediates organ-specific cardiac autoimmunity or participates in the pathogenesis of cardiac-related damage due to systemic conditions, which includes abnormal function of the complement system and its regulatory proteins, pro- and anti-inflammatory cytokine imbalance, and a shift toward T helper 1 and T helper 17 immune responses. Furthermore, systemic inflammation and endothelial dysfunction appear to play a critical role in atherosclerosis. Thus it seems that the immune system plays a pivotal role in the pathophysiology of cardiovascular diseases. In this introductory chapter we discuss the etiology and pathophysiology of autoimmune diseases and elaborate on immune-mediated mechanisms of known cardiovascular diseases.

Keywords

Autoimmunity pathophysiology; Cardiac autoimmunity; Complement imbalance; Cytokines; Th cells

1. Pathophysiology of Autoimmunity

1.1. Etiology of Autoimmunity

A common etiology of virtually all autoimmune diseases is a dysregulated and uncontrolled self-reactive CD4 T-cell response [1]. Several factors are known to affect autoimmunity, including immunologic, infectious, and genetic predispositions. Researchers have acknowledged that many triggers may contribute to the development of autoimmune diseases in susceptible individuals [2]. In recent years we have acquired a better understanding of the pathogenesis of autoimmunity. Although in some cases, the link between specific triggers and an autoimmune disease has been established (ie, the poststreptococcal pharyngitis development of acute rheumatic fever (RF)), in most cases the etiology remains elusive and is considered multifactorial. Autoimmunity may be confined to a specific organ or be associated with a systemic disease with various different clinical manifestations. Importantly, there is an outstanding difference in the prevalence of different autoimmune diseases reported in different countries, further supporting the association between ethnogeographical factors (and presumably different exposure to infectious agents) and autoimmunity [3]. Diabetes mellitus (DM) type 1 is an example of an immune-mediated organ-specific disease that is characterized by a diverse global prevalence. For undetermined reasons, prevalence appears to be higher in North America, northern Europe, and Australia/New Zealand [4]. Herein, we will discuss the multifactorial etiology of autoimmune diseases.

1.1.1. Environmental Factors

Several environmental factors contribute to the development of autoimmune diseases, eg, occupational exposures, drugs, tobacco smoke, silica, organic solvents, dietary intake of certain elements, and exposure to UV light [5,6]. This association was validated in 2010 by an expert panel workshop of the National Institute of Environmental Health Sciences (NIEHS) deliberating on the role of the environment in the development of autoimmune disease [7].

Drugs are important environmental triggers of autoimmunity. The hallmark of drug-induced autoimmunity (DIA) is a systemic lupus erythematosus (SLE)-like phenotype. First described in 1945 in the context of sulfadiazine, it is now recognized that over 90 drugs can induce SLE and other autoimmune diseases, such as vasculitis and arthritis [8,9]. The highest risk for drug-induced lupus erythematosus (DILE) is attributed to procainamide and hydralazine, while quinidine and other drugs are associated with moderate and low risk, respectively [8]. Recently, biological treatments such as the tumor necrosis factor-α (TNF-α) inhibitors and interferon (IFN) have been identified as causing DILE in some patients [9]. As DILE is often reversible, once the offending drug has been removed, early diagnosis and distinguishing DILE from SLE is important [9,10]. However, currently, there are no diagnostic criteria for DILE [8,9]. Identification of a temporal relationship between drug administration and symptom development, as well as symptom resolution after cessation of the drug, is required for diagnosis [10].

Exposure to silica and organic solvents are associated with systemic sclerosis (SSc). Silica may also be associated with the development of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and antineutrophil-cytoplasmic antibody (ANCA)-associated vasculitis [6,7]. Suggested mechanisms for silica-induced autoimmunity include adjuvant effects of apoptotic debris, dysregulation of apoptosis, altered CD4⁺/CD4⁺ CD25⁺ T-cell ratio, and induction of circulating autoantibodies (such as anti-dsDNA, anti-Ro/SSA, anti-La/SSB antibodies in silica associated SLE) [7]. Solvents were found to be associated with circulating SSc autoantibodies (anti-Scl-70), increased IFN-γ, and reduced interleukin (IL)-4 productions [7]. Other substances, such as aromatic amines, hydrazines, hair dyes, aliphatic chlorinated hydrocarbons (vinyl chloride, trichloroethylene, and perchloroethylene), environmental estrogens (such as bisphenol A), inorganic mercury, and the mineral oil component 2-, 6-, 10-, 14-tetramethylpentadecane (TMPD or pristine, which was found to induce acute inflammatory arthritis in rats), are acquired due to occupational exposure, which can also trigger autoimmunity in predisposed individuals [7,11,12]. One suggested mechanism for these substance-induced autoimmune responses is the estrogenic influences on the immune system, which use binding to self-antigens and the creation of neoantigens for which immune tolerance is lacking [3]. Tobacco smoking has been known to be associated with autoimmunity and connective tissue diseases. For instance, the odds ratio (OR) for developing SLE increases by 50% in smokers compared with nonsmokers. The association with ...

Table of contents

• Cover image
• Title page
• Table of Contents
• Dedication
• Copyright
• List of Contributors
• About the Editor
• Preface
• Acknowledgments
• Part I. Immune Medicated Cardiac Injury, Accelerated Atherosclerosis and the Study of Cardiac Involvements in Systemic Diseases
• Part II. Cardiac Manifestations of Inflammatory Arthritis
• Part III. Cardiac Involvement in Autoimmune and Connective Tissue Diseases
• Part IV. Cardiac Manifestations Crystal-Induced Arthritis
• Part V. Cardiac Manifestations of Large Vessel Vasculitides
• Part VI. Cardiac Manifestations of Medium Vessel Vasculitides
• Part VII. Cardiac Manifestations of Small Vessel Vasculitides
• Part VIII. Cardiac Manifestations of Variable Vessel Vasculitides
• Part IX. Post-Infectious Autoimmune Cardiac Diseases
• Part X. Autoinflammation
• Part XI. Therapeutic Approaches: Mechanisms of Action and Cardiac Effects
• Index