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Cytokines

Cytokines in SLE Cytokines produced by the cells of the innate immune system important in SLE pathogenesis include interferon alpha (IFN-α), interleukin (IL)-1, IL-6, tumor necrosis factor (TNF), IL-10, B cell activating factor (BAFF), and a proliferation inducing ligand (APRIL). Cytokines produced by the adaptive immune system include those produced by the CD4 T helper (Th) cells and are IL-2, Th1 cytokines (IFN-γ), Th2 cytokines (IL-4, IL-5,…

The role of dendritic cells in systemic lupus erythematosus

Following the discovery of dendritic cells (DCs) in mice by Ralph Steinman in 1973, the early nineties saw the description of different culture conditions, allowing the generation of large numbers of DC, and energized the study of DCs in both health and disease. Because DCs are the primary line of defense against pathogens that invade the body, they form a critical interface between innate and adaptive…

Neutrophils in systemic lupus erythematosus

Introduction Neutrophils are the most abundant immune-competent cells in the peripheral blood, and represent up to ∼70% of total white blood cells. They play an important role in innate immune responses and are often at the first line of defense against infections. Neutrophils are capable of phagocytosis and produce reactive oxygen species to kill invading microorganisms. They are short lived (half-life ∼7 hours in the circulation, though…

B cells in SLE

Introduction B cells play a central role in the pathogenesis of systemic lupus erythematosus (SLE), including the unique capacity of plasma cells as ultimately differentiated autoreactive B cells to produce autoantibodies. These antibodies reacting against self-antigens participate in the induction and maintenance of tissue damage and represent hallmarks of SLE, which is characterized by the largest variety of specificities, with 180 autoantibodies so far described. The…

T cells

Patients with systemic lupus erythematosus (SLE) develop a chronic autoimmune response against ubiquitous, mostly intranuclear, self-antigens. This response, manifested by the presence of autoantibodies, represents the source of immune complexes and activated T cells that eventually gain access to target organs causing inflammation and damage. T cells are key players in this process. They promote the autoimmune response by providing help to B cells and activating…

Clinical aspects of the complement system in systemic lupus erythematosus

Introduction General comments The complement system is a double-edged sword in lupus ( Fig. 14.1 ). On the one hand, in its absence, a systemic autoimmune disease develops. Thus a complete deficiency of C1q, C1r, C1s, C4, or C2, all early components of the classical pathway (CP), represents a single protein deficiency state that causes lupus. Over 80% of patients with a total C1q or C4 deficiency…

Hormones

Sex hormones Nine out of ten patients afflicted with SLE are women, indicating that the female gender is an important factor in disease development. A skewed X chromosome-inactivation pattern, sex hormone defects, and reproductive history are factors that contribute to the breakdown of tolerance leading to autoimmunity. Several X chromosome defects have been reported in patients with SLE. These include gene translocation causing triplication of genes,…

Monogenic lupus

Introduction The genetic origins of lupus, as reviewed in chapter, Genes and Genetics in Human Systemic Lupus Erythematosus, are extraordinarily complex. Variants in several dozen immune pathway genes are known to contribute to the pathophysiology of SLE. These variants are generally common, with relatively small effect size. Rare variants with strong effect size contribute may be responsible for familial forms of SLE and lupus-like disease, so-called…

Genes and genetics in human SLE

Introduction Many technological advances in the past two decades have led to an explosion of genome wide association studies (GWAS) and subsequent meta-analyses identifying close to 150 novel SLE risk loci across multiple ancestries and in some cases spanning multiple autoimmune diseases. A recent study of 27,574 individuals spanning European, African American and Hispanic Amerindian (HA) ancestries fine-mapped established SLE risk loci, characterized risk loci for…

System lupus erythematosus and the environment

Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by myriad of clinical manifestations, degrees of severity, and alternating phases of remission and flares, that may be defined as a syndrome rather than a single autoimmune disease. The pathogenesis of SLE encompasses complex interactions between genetic susceptibility, immune dysregulation, hormonal, and environmental factors, namely, the mosaic of autoimmunity. The inheritance of genes alone is insufficient…

Overview of the pathogenesis of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) has been labeled “the cruel mystery” by the Lupus Foundation of America. This definition summarizes both the pain and suffering inflicted by the disease and its complex, intricated etiopathogenesis. A key characteristic of SLE is the presence of abnormal immune responses that are favored by susceptible genetic backgrounds and by the environmental exposure to agents only partly recognized. Ensuing immune hyperactivity, mostly…

Socioeconomic aspects of SLE

Introduction Systemic lupus erythematosus (SLE) is a progressive disease necessitating long-term medical care for the prevention or delay of detrimental outcomes. While most medical models often have an individual focus, diagnosing each patient’s symptoms and recommending treatment regimens, the reality for patients with SLE is much more complicated. In this chapter, we explicate the social, cultural, and economic forces that affect risk and health outcomes among…

Disease development and outcome

Historical perspective Systemic lupus erythematosus (SLE) is a disease of exacerbations and remissions with variable course and prognosis. There were no criteria to classify SLE before the early 1970s, and no standardized method to evaluate disease activity, flares, or remissions existed until the 1980s. SLE patients had a poor prognosis with a 5-year survival rate of only 55% in 1955. Corticosteroid treatment was introduced in 1948,…

Epidemiology

Introduction Systemic lupus erythematosus (SLE) is a complex multisystemic autoimmune disease characterized by a wide spectrum of clinical manifestations, overabundant immunological and laboratory abnormalities, and a variable course and outcome. Descriptive, observational and experimental studies, and a few population-based ones have used classification criteria to include patients with similar clinical and laboratory abnormalities and are the basis for the epidemiological data currently available. In 1982 the…

The patient

Any idiot can prescribe antibiotics to treat an ear infection, but that’s not what makes you a good physician. Dr Levana Sinai in Vital Conversations: Improving Communications Between Doctors and Patients Health care providers are usually good at keeping up with the pathophysiology, diagnosis, and management of diseases. Yet, we typically spend little time learning how to best communicate with patients. In fact, many of us…

History of systemic lupus erythematosus with an emphasis on certain recent major issues

History of clinical observations The clinical history of systemic lupus erythematosus (SLE) is interesting and torturous. It took more than 150 years for clinicians to describe the characteristics of all involved organs. The detailed histories of SLE from Hippocrates to Osler and from 600 AD to the mid-1970s have been described by Smith and Cyr and by Benedek, respectfully. Here only the highlights of clinical history will…

New Biological Avenues for Sjögren’s Syndrome

Acknowledgment We thank Dott Antonina Minniti for her help in preparing the manuscript. The introduction of biological treatments that target leukocytes and their cytokine products has led to a major change in the management of immune-mediated inflammatory diseases, among them Sjögren’s syndrome (SS). The recent improved understanding of the mechanisms involved in SS pathogenesis and persistence has prompted the development of new classes of drugs aimed…