Katerina Koether, Valérie Besnard, Hilary Sandig, Alan Carruthers, Elena Miranda, Sabine Grootenboer-Mignot, Camille Taillé, Sylvie Chevret, Dominique Valeyre, Hilario Nunes, Dominique Israel-Biet, Wei Keat Lim, Vincent Cottin, Dominic Corkill, Claire Dobson, Maria Groves, Franco Ferraro, Edouard Guenzi, Ling Huang, Michal Sulikowski, Arnaud Mailleux, Lynne Anne Murray, Thomas Mustelin, Ian Strickland, Matthew A Sleeman, Bruno Crestani
Several reports have highlighted a potential role of autoreactive B-cells and autoantibodies that correlates with increased disease severity in patients with idiopathic pulmonary fibrosis (IPF). Here we show that patients with IPF have an altered B-cell phenotype and that those subjects who 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 introducing antibodies targeting the endogenous protein PPL (mimicking naturally occurring autoantibodies seen in patients) directly in the lung increases lung injury, inflammation, collagen and fibronectin expression through direct activation of follicular dendritic cells, which in turn activates and drives proliferation of fibroblasts...
May 2023: European Respiratory Journal