RAiD 10.26259/7f4ab9b5

The UNFOLD study - Investigating immunotherapy for chronic lung disease

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      "text": "The UNFOLD study - Investigating immunotherapy for chronic lung disease",
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      "text": "The highly variable clinical outcomes have made it difficult to identify the precise mechanisms involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and thus the development of a specific cure or treatment to halt and reverse the inexorable decline in patient health. Chronic inflammation is a cardinal feature of IPF and is driven by both innate and adaptive immune responses. We recently demonstrated a potential role for antibody secreting plasma B cells (PCs) in the development of bleomycin-induced lung fibrosis in mice. Human studies also showed both elevated serum autoantibodies and elevated numbers of antibody secreting cells in IPF blood, and the accumulation of mature PCs adjacent to areas of active lung fibrosis in IPF lung tissue, supporting a functional role for PCs in IPF pathogenesis. We have used a multi-omics approach to examine the B cell repertoire of a subset of IPF patients and age-matched controls as well as screening IPF patient sera against a proteomic array to identify potential human autoantigens. We have shown that the B cell repertoire in IPF differs to that of control patients, with IPF patients displaying a restricted antibody repertoire compared to controls and evidence of B cell clonal expansion. We have identified a range of novel autoantigens in a subset of IPF patients. These findings suggest an approach for stratifying IPF patients based on an autoimmune phenotype that may inform treatment options for some of these patients. The UNFOLD study investigates the potential of immunotherapy for this chronic lung disease and specifically will 1) Validate specific common autoantigens using larger, geographically disparate IPF patient cohorts. 2) develop more appropriate and sensitive screening assays for early diagnosis and stratification to identify autoimmune IPF patients and 3). Test the suitability of novel plasma cell-specific B cell ablation and CAR-T cell therapy approaches in pre-clinical models of lung fibrosis.",
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