Background: IPF is a progressive disease characterized by fibrosis and inflammation. The cytoskeletal protein vimentin is upregulated in IPF and can be citrullinated by activated macrophages. This study aimed to assess the potential of two serological neo-epitope biomarkers in IPF reflecting degradation of non-citrullinated (VIM) or citrullinated (VICM) vimentin.

Methods: VIM and VICM levels were measured by ELISA in serum from IPF patients at baseline (n=203), 6-, and 12-months. These biomarkers target the same amino acid sequence, except for a citrulline conversion at one position. Patients were divided in quartiles according to their baseline biomarker levels and associations were established with pulmonary function measurements (FVC and DLCO) and 6-minute walk distance (6MWD). Disease progression was defined as an absolute decline of ?5% in FVC or ?10% in DLCO or death at 12-months. Data was analysed using ANCOVA or linear mixed models adjusted for age and gender.

Results: At baseline, patients with higher VICM serum levels (Q4) had a 5.3% (p=0.042) lower DLCO% compared to those in Q2 and a shorter 6MWD than those in Q1 (?51.1 m, p=0.009). Moreover, patients with high VIM serum levels (Q4) had a 9% lower FVC% compared to Q1 (p=0.020). Contrary to VIM, VICM levels were higher in progressive patients at baseline (p=0.007) and 6-months (p=0.033), compared to stable patients.

Conclusions: While VIM measures vimentin degradation, VICM includes a citrullination and reflects macrophage activity. Interestingly, VICM but not VIM was specifically related to IPF progression. This study highlights the importance of measuring the right neo-epitope when assessing IPF pathology.