Autoantibodies are associated with disease progression in idiopathic pulmonary fibrosis

Abstract

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.

Mathematical modeling in autoimmune diseases: from theory to clinical application

“…It should be noted that the etiology and role of autoimmunity in the development and progression of these diseases are still unknown. However, genetic predisposition and external triggers such as infection, inorganic materials, and environmental factors are likely to lead to the development of an autoimmune response (109)(110)(111)(112). Mj and lymphocytes are key players involved in the initiation of the immune response in the lung, in both indications: Mj, serving as scavenger cells, ingesting and degrading the inhaled antigenic load, initiate a typical Th1 immune response.…”