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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…

Novel Therapeutic Strategies in Sjögren’s Syndrome: T-Cell Targeting

In the past decade, the treatment of autoimmune diseases [such as rheumatoid arthritis (RA) and Crohn disease] has fundamentally changed with the introduction of targeted therapies. On the contrary, the treatment of Sjögren’s syndrome (SS) and especially the eye and mouth dryness that are its main manifestations has remained purely symptomatic and the systemic effects, such as inflammatory arthritis continue to be treated with nonspecific immunosuppressive…

Novel Therapeutic Strategies in Sjögren’s Syndrome: B-Cell Targeting

1 Therapeutic Potential for B-Cell Modulation in Sjögren’s Syndrome Critical dysregulated immune pathways, including the key role of B cells as well as the ectopic lymphoneogenesis, are involved in primary Sjögren’s syndrome (pSS) pathogenesis. B cells may provide a critical link between the development of tertiary lymphoid tissue within target tissues and the propagation of the autoimmune process. Although the peculiar role of B cells in…

Outcome Measures in Sjögren’s Syndrome and Perspectives in Clinical Trial Design

1 Current Outcome Measures in Primary Sjögren’s Syndrome 1.1 Symptoms Evaluation of the three main symptoms of primary Sjögren’s syndrome (pSS): dryness, pain, and fatigue, is pivotal, because these concerns are shared by all patients with pSS, in contrast to systemic complications, which affect approximately 30% of patients. Individual visual analog scales (VASs), ie, pain and fatigue VASs, represent the only way to assess patients’ symptoms.…

Autoantibodies and Autoantigens in Sjögren’s Syndrome

1 Background of Autoantibodies SSA/B Initial pioneering studies in systemic lupus erythematosus (SLE) noticed that patient sera could react with the nucleus of acetone-fixed nucleated cells using an immunofluorescent assay (IFA) ( Fig. 16.1 ). A series of different patterns of reactivity (ie, diffuse, fine-speckled, large-speckled, etc.) were noted and associated with distinct clinical features. The autoantibodies that produced each pattern were named by investigators at…

Cytokines, Chemokines, and the Innate Immune System in Sjögren’s Syndrome

1 Introduction Cytokines are the mediators of the immune system. They are small proteins of around 25 kD that are produced in response to a stimulus (ie, invading microbes) by numerous cell types. They mediate and regulate immune responses, inflammatory reactions, wound healing, hematopoiesis, and chemotaxis, and can be divided into being proinflammatory or antiinflammatory. Their mechanism of action is via specific receptors and can either…