Specific Antigens and Autoimmunity in Interstitial Pulmonary Disease

Background

We investigate Sarcoidosis and Idiopathic Pulmonary Fibrosis, IPF, to find markers for early fibrosis development. The aetiologies for both diseases are unknown and there is no specific treatment, moreover, there is a lack of diagnostic biomarkers for both diagnose and disease activity. Overall, the diseases have a substantial impact on patients’ health status and quality of life. To identify patients at risk of rapid development of fibrosis is key to improve patient care.

Aims

We hypothesize that identification of specific antigens can result in the elucidation of the pathogenesis of sarcoidosis as well as of IPF, and the development of new individualized treatments. Our aims are therefore to: - Identify new immune targets (cells, cytokines) for treatment. - Identify peptides (externally derived or auto-antigens) capable of stimulating T cells and/or T cell hybridomas.

- Identify key markers of specific inflammatory responses in sarcoidosis and IPF. Work Plan

In the clinic, we routinely screen patients to be eligible for research, the lung clinic Karolinska Sjukhuset has thus provided us with a substantial sample assembly to be used in research. In addition, our collaborators in France and Netherlands has delivered additional samples for analysis. Consequently, this project accesses a larger cohort than any previous research study in this area.

The samples are analyzed using a high-throughput method called multiplex bead array analysis (mSBA) with the potential to screen for presence of thousands of antibodies/proteins in one single sample. Candidate antigens will be selected for BAL cell stimulation analyses. Significance

The overall aim of the study is to identify biomarkers or auto-antigens involved in these pulmonary diseases by using powerful proteomic approaches. To date there is no fail-safe diagnostic test to determine the severity or outcome of disease, as well as no specific treatments. This unquestionably results in lower quality of life for patients.

Establishing candidate autoantigens would give a better understanding of the pathophysiology, and potentially result in improved diagnostics, new treatments and therefore benefit the patients.