Antigens of diagnostic relevance in autoimmunity: characterization, production strategies and immunoassays development​ .

Autoimmune disorders (AID) represent a group of chronic and heterogeneous diseases, whose common trait is the immune system reaction against self-components of the organism. Most of the AID have unknown etiology, but it was demonstrated that both genetic and environmental factors are involved in triggering the pathologic mechanism. Because of their chronicity and their debilitating complications, AID have high medical and socioeconomic costs, leading to the crucial necessity to perform an early diagnosis and to monitor the disease follow up. Unfortunately, the available diagnostic and prognostic instruments are often complicated and invasive. In order to develop diagnostic and/or prognostic tools marked by low-invasivity, low-cost, and easy execution, it is crucial to detect trustworthy biomarkers (BM). The BM characterization has a significant importance also because it represents a powerful instrument to disclose the molecular mechanisms involved in the ethiopathogenesis of the disorder of interest. In this context, the main goal of this work is to identify the target(s) of the humoral autoimmune response using the chemical reverse approach, which involves the screening of focused Ag libraries with pts serum. Indeed, in the case of autoimmunity, an easily detectable and reliable BM may be represented by the titer of a specific auto-Ab. A key feature of this study is the evaluation of the role of aberrant post-translational modifications (PTM) in autoimmunity, as it was hypothesized that environmental agents may induce the occurrence of non-natural PTM on self-proteins, uncovering neo-epitopes and triggering the autoimmune response. In particular, the attention was focused on two main topics, which will be treated separately within this presentation: the role of Myelin Oligodendrocyte Glycoprotein (MOG) as putative auto-Ag in central nervous system AID (Chapter 2); investigation of the involvement of aberrant PTM in the ethiopathogenesis of Primary Biliary Cirrhosis (Chapter 3).