Autoantibodies are associated with disease progression of idiopathic pulmonary fibrosis.

Several reports have highlighted a potential role of auto-reactive B cells and autoantibodies that correlates with increased disease severity in patients with IPF. Here we show that patients with IPF have an altered B cell phenotype and that those subjects that have autoantibodies against the intermediate filament protein periplakin (PPL) have a significantly worse outcome in terms of progression free survival. Using a mouse model of lung fibrosis, we demonstrate that the instillation of antibodies targeting the endogenous protein PPL, mimicking naturally occurring autoantibodies seen in patients, directly to the lung increased lung injury, inflammation, collagen and fibronectin expression, through direct activation of follicular dendritic cells which in turn activates and drive proliferation of fibroblasts. This fibrocyte population was also observed in fibrotic foci of patients with IPF and increased in peripheral blood of IPF patients compared to aged matched control. This study re-iterates complex and heterogeneous nature of IPF, identifying new pathways that may prove suitable for therapeutic intervention.