Autoantibodies discovered as potential biomarkers in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is currently an incurable disease that is usually fatal within two to five years of diagnosis. Although newly approved anti-fibrotic drugs such as pirfenidone and nintedanib can slow the progression of the disease, lung transplantation remains the only definitive treatment option for IPF.

DZL scientists led by Dr Herbert Schiller from Helmholtz Munich have discovered that autoantibodies also occur in IPF patients. The researchers assume that they are suitable as biomarkers for predicting the course of the disease because the presence of certain autoantibodies was associated with a reduced survival rate.

Interstitial lung diseases caused by autoimmunity, such as connective tissue-related interstitial lung disease (CTD-ILD), have a better prognosis. Patients with these diseases have autoantibodies, which doctors can use to diagnose and classify the disease.

Until now, it was assumed that inflammation and autoimmunity play no role in IPF. However, more recent studies show that autoimmunity could also be involved in IPF. The researchers wanted to investigate this previously little-known role of autoantibodies in developing and progressing IPF using autoantibody profiles.

Analysing data with a newly developed method

The researchers used previously published data sets to investigate which antibodies occur in IPF and CTL-ILD patients during the disease. They developed a test based on mass spectrometry to create the autoantibody profiles.

The study showed a significant increase in antibodies in patients with idiopathic pulmonary fibrosis. A specific autoimmune signature was identified that is associated with shorter transplant-free survival in IPF patients, and that persists over time. It was particularly striking that autoantibodies against a specific protein were associated with a lower survival rate. This suggests that these autoantibodies could serve as biomarkers for predicting the course of the disease.

Concept of protective autoimmunity

The study also uncovered autoreactivities that were associated with improved disease progression. Recently, the concept of protective autoimmunity has been introduced in COVID-19. This is based on discovering that autoantibodies against specific chemokines are associated with favourable disease outcomes. It also showed they could reduce the likelihood of developing long COVID one year after infection. The researchers believe applying their newly developed test to the COVID-19 context and autoimmunity after viral infection could be interesting and promising.

Further exploring the role of autoantibodies in IPF

The unexpectedly high prevalence of autoantibodies in idiopathic pulmonary fibrosis shows that further research is needed to understand the possible role of autoantibodies in disease development or their potential protection for patients, the authors write. Patients with autoantibodies associated with a worse disease course should also be clinically investigated in more detail.

Original publication: Leuschner G, Semenova A, Mayr CH, et al. Mass spectrometry-based autoimmune profiling reveals predictive autoantigens in idiopathic pulmonary fibrosis. iScience. 2023;26(11):108345. published 2023 Oct 27. doi: 10.1016/j.isci.2023.108345