The role of autoimmunity and inflammation in chronic disease

Chronic diseases (CDs), are the leading cause of morbidity and mortality in developed countries and, increasingly, in developing countries as well. Among CDs, cardiovascular diseases (CVD), and psychiatric and musculoskeletal conditions are some of the prime contributors to their associated burden. Whilst atherosclerotic related outcomes are responsible for majority of CVD deaths, disorders such as depression and osteoporosis are the major contributors to non-fatal burden. Subsequently, the latter conditions form the CDs considered in this thesis. By 2020, CDs are forecasted to account for three-quarters of mortality worldwide, an increase largely attributed to an ageing population. Autoimmune disease sufferers incur an increased risk and a worse outcome in the case of CVDs. Similarly, this cohort suffers from depression more often than healthy individuals, an association that cannot be completely accounted for by the psychological impact of the disease. Likewise, autoantibodies are linked to the pathophysiologic changes characteristic of osteoporosis, a common complication amongst autoimmune conditions. It is however unclear to what extent autoantibodies are responsible for those chronic manifestations. The aim of this thesis is therefore to tease out the role of autoantibodies in CD development by contrasting their effects in clinical and nonclinical populations. Briefly, chapter 1 shall outline the direction of this research, providing background highlighting the importance of this body of work and intended study objectives. Chapter 2 provides the theoretical context, recapping what has already been accomplished and highlighting the gaps in our knowledge. Chapter 3 describes the sample and dataset utilised for the purpose of the research presented in the successive three chapters (4, 5 and 6) which comprise primary investigations examining the role of autoantibodies in CD pathogenesis amongst a population-based cohort of elderly Australians. The final chapter is a synthesis of the findings and limitations from each study, with recommendations for future research.