Objectives of this work package
- The identification of autoantibody profiles associated with disease activity and susceptibility to infection
- A proteomic analysis of autoantibody response in immune-mediated disease
- The identification of serum proteome markers of disease activity or clinical outcome in patients with immune-mediated disease
Description of the tasks
This Work Package seeks to identify proteins or patterns of proteins, including antibodies, that predict the outcome of chronic autoimmune and inflammatory disease. Clinical samples from patient cohorts with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), inflammatory bowel disease (IBD) and/or rheumatoid arthritis (RA) will be analysed using different methods.
 Partner KTH will screen serum samples from patients with immune-mediated diseases using high-density arrays of both cell surface and secreted proteins. These arrays will be generated by utilizing the human protein fragments generated within the Human Protein Atlas project, which is a unique, large-scale effort and resource dedicated to produce a repository of representative products of all protein-coding human genes. Patterns of autoantibodies correlating with clinical parameters uncovered using this approach will be validated in additional patient cohorts using focussed bead-based arrays.
Partner UU will investigate autoantibody responses using novel proteomic approaches. These approaches will enable the quantification of both pathogenic and therapeutic antibodies in patient sera which in turn will be related to clinical outcome measures including time to disease remission and risk of relapse.
Partner UCAM aims to identify proteomic markers of disease and treatment response in patients with AAV sampled both prior to and post treatment using serum proteome analysis. Serum biomarkers identified using this approach will be validated in additional patient cohorts as well as extended to other disease indications.
The results will help to inform the pathway analyses of autophagy, mechanisms of immunosenescence and the role of T cells in autoimmunity to MPO in WP 1, 3 and 4.
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