Susan Manzi

The complement system is arguably linked more intimately to SLE than to any other human disease. This association has been recognized for decades and was viewed as inexplicably paradoxical. Discoveries made during the past several years have begun to explain this perplexing link between complement and SLE and have concomitantly identified potential strategies and opportunities for mining the complement system for lupus genes, biomarkers, and therapeutics. In this chapter, we will review the biology of the complement system in relation to SLE, summarize common methods for measurement of complement, revisit the utility of complement assays in clinical management of SLE, and consider the potential for targeting the complement system for therapeutic intervention.

Systemic lupus erythematosus (SLE) can involve the cardiovascular system in numerous ways, with manifestations ranging from subclinical to fulminant organ involvement. Associated immune dysregulation and antibody and immune complex formation can attack any part of the cardiovascular system. This chapter will review the clinical presentation, diagnosis, and treatment of SLE-associated diseases of the cardiovascular system.

In 2011 systemic lupus erythematosus was officially recognized as a unique risk factor for cardiovascular disease (CVD) by the American Heart Association. While modern therapies have prolonged the lives of lupus patients, their risk for CVD is increased at a rate that traditional CVD risk factors alone cannot explain. This chapter reviews the recent research on disease biomarkers and risk-calculators in conjunction with imaging techniques that have shown subclinical atherosclerosis prior to the development of symptoms in patients with lupus. We also discuss relevant drug trials on antimalarials, immunoregulators, statins, and aspirin and their effect on CVD in patients with lupus.

Systemic lupus erythematosus was officially recognized as a unique risk factor for cardiovascular disease (CVD) in 2011. Modern therapies extend the lifespan of lupus patients, but their risk for CVD is far greater than typical cardiovascular risk factors can explain. Imaging technologies have shown that subclinical manifestations of the disease in lupus patients begin long before symptoms are reported. This chapter considers the recent advances in research and therapeutic paradigms for atherosclerotic CVD in lupus patients and summarizes the same for other cardiac manifestations. Randomized, placebo-controlled clinical trials for CVD intervention in lupus patients are lacking, but statins, antimalarials, immunoregulatory agents, antioxidants, and oral hypoglycemic agents have been explored. Here, relevant drug trials are reviewed and the research into disease biomarkers is discussed.

Measurement of serum C3 and C4 has been used for several decades to monitor disease activity in patients with SLE. Despite the limited utility and recognized weaknesses of these assays, they have remained the gold standard during an era of unprecedented discovery in the complement field. The current urgent need for lupus biomarkers warrants efforts to mine the complement system for assays superior to serum C3 and C4. Recent studies of soluble and cell-bound complement activation products hold promise for achieving this goal.

This chapter discusses lung disease in lupus. Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease that primarily affects women in the reproductive years, with various clinical presentations caused by the production of autoantibodies and the formation of complement-fixing immune complexes. Pulmonary complications, one of the predominant features of SLE, occur in more than half of the patients at some time during the course of their disease. In many cases, lung complications are not detected until autopsy, indicating that they are often not clinically evident. The general classification of pulmonary manifestations and their prevalence are summarized in the chapter. The chapter reviews the epidemiology, clinical presentations, differential diagnosis, management, and outcome of the broad spectrum of pulmonary complications experienced by patients with SLE.

This chapter presents an overview of the disease manifestations and treatments for systemic lupus erythematosus (SLE). SLE is a chronic inflammatory autoimmune disease that occurs predominantly in women during their childbearing years. The disease course is marked by exacerbations and remissions. This multisystem disease is characterized by the production of auto-antibodies and the occurrence of tissue damage from the deposition of the antibodies in immune complexes. Immune dysregulation probably occurs from environmental triggers in the genetically susceptible host. Diagnosis is generally not difficult when many typical symptoms and signs are present but may be more problematic when the disease manifests as only a few complaints or when problems occur over time. Therapeutic options for SLE offer increasing hope. For the first time since the 1970s, clinical trials in lupus are being conducted. Drugs that have been used in other diseases are finding new use in lupus. Results from clinical trials indicate that dehydroepiandrosterone (DHEA) treatment improves SLE disease activity and reduces corticosteroid requirements. The prolactin antagonist bromocriptine shows promise in suppressing active SLE. Clinical studies indicate that bromocriptine decreases serum prolactin levels, suppresses anti-dsDNA antibodies, significantly reduces lupus disease activity, and reduces SLE flares.