[1/8] Mass spectrometry for autoantibody profiling of patient body fluids. Pre-print out on @medrxivpreprint - A proteomics workflow reveals predictive autoantigens in idiopathic pulmonary fibrosis. @HelmholtzMunich@labs_mann
Tweetorial below...
[2/8] We have previously discovered an unexpected high prevalence of tissue resident MZB1+ plasma cells in lung and skin fibrosis. The number of these cells was associated with lung function decline and tissue IgG in IPF.
[3/8] We speculated that the high prevalence of fibrosis associated plasma cells in IPF represents autoreactive B cell clones producing autoantibodies. Indeed, autoantibodies of unknown significance have been repeatedly detected in IPF patients.
[4/8] We developed the Differential Antigen Capture assay, showing similar sensitivity and specificity as a clinically approved ELISA for the scleroderma antigen Scl-70, while at the same time discovering a multitude of autoantigens due to its unbiased and multiplexed nature.
[5/8] We compared the autoantibody profiles of patients with connective tissue disease associated lung fibrosis (CTD-ILD) and IPF from two independent cohorts. Surprisingly, the prevalence of autoantibodies was higher in IPF as in CTD-ILD with known autoimmune aetiology.
[6/8] Our results suggested that a break of immune tolerance is a common theme in IPF. We identified a specific set of autoreactivities, most notably to the secreted glycoprotein THBS1, that were predictive for reduced transplant free survival independently in both cohorts.
[7/8] In conclusion, we have developed a novel proteomic assay for unbiased autoantibody profiling that can be used in various clinical scenarios, including the currently ongoing discussion on a potential role of autoantibodies in (long) COVID-19.