Circulating Immune Cells as Biomarkers for Idiopathic Pulmonary Fibrosis

Patients with fibrotic lung diseases*, such as idiopathic pulmonary fibrosis (IPF), show progressive worsening of lung function with increased shortness of breath and dry cough. To-date, this process is irreversible, which is why scientists are searching for novel biomarkers or indicators, which enable earlier diagnosis of this disease, with the aim to better interfere with disease progression.

A team of scientists at the Comprehensive Pneumology Center (CPC) at Helmholtz Zentrum München headed by Professor Oliver Eickelberg, Chairman of the CPC and Director of the Institute of Lung Biology as well as the DZL at the Munich partner site, have now discovered that myeloid-derived suppressor cells (MDSC)** may serve as such biomarkers. “The role of MDSC has been most extensively studied in cancer, where they suppress the immune system and contribute to a poor prognosis,” explained first author Isis Fernandez, MD. The current study suggests that similar mechanisms are also at work in IPF.

In collaboration with the Department of Internal Medicine V (Director: Professor Jürgen Behr) of the Munich University Hospital, the team examined blood samples of 170 study participants, including 69 IPF patients, in terms of the composition of circulating immune cell types. In each patient, these were correlated with lung function. Strikingly, the MDSC count in IPF patients was significantly higher than in the healthy control group. At the same time, the researchers observed that there was an inverse correlation between lung function and circulating MDSC counts: the poorer the lung function, the higher the MDSC count. In control groups of patients with chronic obstructive pulmonary disease (COPD) or other interstitial lung diseases, this inverse correlation was not found. “We conclude that the number of MDSC reflects the course of the disease, especially in IPF,” said Fernandez.

To obtain an indication of whether the cells themselves could be the cause of the deterioration in lung function, the researchers measured the activity of genes that are typically expressed by immune cells. They found that these genes were expressed less frequently in samples that exhibited high MDSC counts. This indicates that MDSC – similar to their role in cancer – also compromise the immune system in IPF, according to the scientists.

A look into the lung tissue of IPF patients supports this assumption. “We were able to show that MDSC are primarily found in fibrotic niches of IPF lungs characterized by increased interstitial tissue and scarring, that is, in regions where the disease is very pronounced,” said Eickelberg. “As a next step, we seek to investigate whether the presence of MDSC can serve as a biomarker to detect IPF and to determine how pronounced it is.” In addition, the researchers want to investigate the mechanisms of accumulation in more detail. “Controlling accumulation or expansion of MDSC or blocking their suppressive functions may represent a promising treatment options for patients with IPF,” said Eickelberg.

Further Information

Background:
*Fibrotic lung diseases are characterized by an increase of connective tissue in the lung, which hardens and becomes scarred. This stiffening is accompanied by a disturbed regeneration of the lung which in turn is associated with deteriorating lung function. The quality of life for these the patients is significantly limited.

**Myeloid-derived suppressor cells are a heterogeneous group of immune cells of the hematopoietic system, which in the healthy system play a role in tissue renewal and immune response.

Original Publication:
Fernandez, I. et al. (2016). Peripheral blood myeloid-derived suppressor cells reflect disease status in idiopathic pulmonary fibrosis, European Respiratory Journal, DOI: 10.1183/13993003.01826-2015
http://erj.ersjournals.com/content/early/2016/08/31/13993003.01826-2015

As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,300 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. http://www.helmholtz-muenchen.de/en/index.html

The Comprehensive Pneumology Center (CPC) is a joint research project of the Helmholtz Zentrum München, the Ludwig-Maximilians-Universität with its University Hospital and the Asklepios Fachkliniken München-Gauting. The CPC's objective is to conduct research on chronic lung diseases in order to develop new diagnosis and therapy strategies. The CPC maintains a focus on experimental pneumology with the investigation of cellular, molecular and immunological mechanisms involved in lung diseases. The CPC is one of five sites of the German Center for Lung Research (Deutsches Zentrum für Lungenforschung, DZL). http://www.helmholtz-muenchen.de/en/ilbd/index.html

Munich University Hospital (LMU) treats around 500,000 outpatients, inpatients and semi-residential patients each year at its Großhadern and City Centre Campuses. Just over 2,000 beds are available to its 28 specialist clinics, twelve institutes and seven departments, and its 47 interdisciplinary centres. Of a total of 9,500 employees, around 1,600 are doctors and 3,200 are nursing staff. Munich University Hospital has been a public-law institution since 2006. Together with the Medical Faculty of Ludwig Maximilians University, Munich University Hospital is involved in four special research areas of the German Research Foundation (SFB 684, 914, 1054, 1123), three Transregios (TRR 127, 128, 152) belonging to Clinical Research Group 809, and two Graduate Colleges belonging to the German Research Foundation (GK 1091, 1202). This is in addition to the Center for Integrated Protein Sciences (CIPSM), Munich Center of Advanced Photonics (MAP), Nanosystems Initiative Munich (NIM) and Munich Cluster for Systems Neurology (SyNergy) – all institutes of excellence – and the Graduate School of Systemic Neurosciences (GSN-LMU), the Graduate School of Quantitative Biosciences Munich (QBM) and the Graduate School Life Science Munich (LSM). http://www.klinikum.uni-muenchen.de

The German Center for Lung Research (DZL) pools German expertise in the field of pulmonology research and clinical pulmonology. The association’s head office is in Giessen. The aim of the DZL is to find answers to open questions in research into lung diseases by adopting an innovative, integrated approach and thus to make a sizeable contribution to improving the prevention, diagnosis and individualized treatment of lung disease and to ensure optimum patient care. http://www.dzl.de/index.php/en

Contact for the media:
Department of Communication, Helmholtz Zentrum München – German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg – Tel. +49 89 3187 2238 – Fax: +49 89 3187 3324 – E-mail: presse@helmholtz-muenchen.de

Scientific contact at Helmholtz Zentrum München:
Prof. Dr. Oliver Eickelberg, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Comprehensive Pneumology Center, Max-Lebsche-Platz 31, 81377 München, Tel. +49 89 3187 4666 – E-mail: oliver.eickelberg@helmholtz-muenchen.de