ENHANCING DIAGNOSIS AND MANAGEMENT OF SYSTEMIC LUPUS ERYTHEMATOSUS

Systemic lupus erythematosus (SLE) affects a significant portion of young women of childbearing age worldwide, in particular those of non-white descent. In the United States, the incidence ranges 8.1-11.4 per 100,000 among African-American, and 2.5-3.9 per 100,000 among Caucasian women. The prevalence is estimated 56-283 per 100,000 among African-American, and 17-71 per 100,000 among Caucasian women. Understanding the natural history of systemic lupus, its major complications such as cardiovascular disease and associated risk factors, identifying major biomarkers for timely and accurate diagnosis of the disease itself and its manifestations is of great public health importance, since this will help to reduce morbidity and mortality among lupus patients.The dissertation consists of three relevant chapters. The first chapter is an overview of candidate biomarkers for diagnosis of SLE. It includes a brief review of the role of complement molecules in SLE pathogenesis, evaluation of the past and current uses of complement in monitoring SLE disease activity, and summary of recent findings that propose a novel method of measuring complement activation to specifically and sensitively diagnose SLE. The chapter concludes by discussing how this method may also support the resurgence of complement as a valuable biomarker of SLE disease activity.The second chapter is the cost effectiveness analysis of the novel diagnostic biomarker discussed in chapter one. The analysis shows that using the novel diagnostic biomarker along with the traditional tests can be cost effective for the population of patients contemplating SLE. Chapter three is devoted to atherosclerosis as a major complication of SLE and to coronary calcification measured by electron beam tomography (EBT) as a major biomarker of subclinical atherosclerosis. The risk factors associated with subclinical vascular disease in women with SLE are also reported. It is concluded that atherosclerosis of the coronary arteries detected by EBT is highly prevalent in patients with SLE and is related to many potentially modifiable traditional, SLE-specific and inflammatory risk factors for vascular disease