The Role of Microparticles as Biomarkers in the Development of Therapy for Autoimmune Disease
Autoimmune diseases are a diverse group of conditions that result from abnormalities in immune cell function that culminate in tissue inflammation, destruction, or dysfunction. Despite advances in immunomodulatory and anti-inflammatory therapy, the develo
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troduction Autoimmune diseases are a diverse group of conditions that result from abnormalities in immune cell function that culminate in tissue inflammation, destruction, or dysfunction [1, 2]. These conditions can cause highly discrete tissue involvement as exemplified by organ-specific autoimmune diseases such as multiple sclerosis or type 1 diabetes or more generalized tissue involvement as exemplified by systemic inflammatory diseases such as systemic lupus erythematosus (SLE). At present, whatever the pattern of tissue involvement, the treatment of the immune component of these diseases utilizes similar agents to either curtail inflammation or to attenuate T and/or B cell reactivity [3]. If damage is irreversible, however, then treatment involves agents that restore to the extent possible the functional impairment that results from unopposed autoimmune attack. While the etiology and clinical manifestations of autoimmune diseases may vary, the development of new therapies confronts many similar challenges especially in the setting of clinical trials. A particularly serious and vexing challenge relates to biomarkers. For most autoimmune diseases, studies on both patients and animal models have documented a host of phenotypic and functional immune cell abnormalities [4]. Translating these observations into the creation of reliable and actionable markers for use in clinical trials has been difficult, however. Furthermore, as “big data” approaches
D.S. Pisetsky, MD, PhD Division of Rheumatology and Immunology, Department of Medicine, Duke University Medical Center, Durham, NC, USA Medical Research Service, VA Medical Center, Durham, NC, USA Duke University Medical Center, Durham VA Medical Center, 508 Fulton Street, 151G, Durham, NC 27705, USA e-mail: [email protected] © Springer International Publishing Switzerland 2017 P. Mina-Osorio (ed.), Next-Generation Therapies and Technologies for Immune-Mediated Inflammatory Diseases, Progress in Inflammation Research, DOI 10.1007/978-3-319-42252-7_3
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become more common, the number of biomarkers will undoubtedly rise dramatically; the complexity of these markers will also grow as each marker becomes a composite of thousands or even millions of data points [5–7]. The gap between the biomarkers of today (e.g., C-reactive protein, erythrocyte sedimentation rate, cytokine levels) and those projected for the future (e.g., RNA- seq of individual cells at the site of tissue injury) is enormous, and it will take years before the promise of big data is realized. During the transition from little to big data, the development of new therapies may benefit by some intermediate approaches which can provide a more granular picture of the immune system disturbances associated with autoimmune disease. The value of such approaches will be increased if they can employ instrumentation readily available in most clinical laboratories. Among these approaches, the analysis of microparticles holds great promise as a platform for the development of new biomarkers to a
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