Autoantigen identification in ANA-positive usual interstitial pneumonia without known autoantibody through immunoprecipitation-mass spectrometry

Extract Screening for autoantibodies is an essential part of the work-up of interstitial lung disease (ILD) as detection of specific autoantibodies can lead to timely diagnosis and treatment of an underlying systemic autoimmune disease (SAD). In practice, screening for autoantibodies is mostly done with the HEp-2 indirect immunofluorescence assay (HEp-2 IIFA), often referred to as the antinuclear antibody (ANA) test, together with solid-phase assays for the most common SAD-associated autoantibodies. A positive HEp-2 IIFA without detection of a specific autoantibody in a patient with a radiographic usual interstitial pneumonia (UIP) pattern on high-resolution chest tomography (HRCT) is a common clinical scenario. In absence of overt clinical features associated with SADs or other definite causes of ILD, most of these patients are diagnosed with, and thus managed as, idiopathic pulmonary fibrosis (IPF). However, these patients could have clinically relevant autoantibodies against rare SAD-associated autoantigens for which no test is widely available, as the UIP pattern is also common in ILD associated with SADs [1]. Alternatively, these patients could have autoantibodies against hitherto unidentified autoantigens. In this study we aimed to identify underlying protein autoantigens in patients with ANA-positive ILD with a radiographic UIP pattern without known specific autoantibody through a novel immunoprecipitation-mass spectrometry (IP-MS) approach [2].