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Lung Research

Is idiopathic pulmonary fibrosis due to an autoimmune disorder?

The exact cause of certain forms of pulmonary fibrosis remains unknown, but as a new study published in the ‘American Journal of Respiratory and Critical Care Medicine’ has shown, autoimmune reactions may be a causal factor in more patients as currently expected. The study was conducted by scientists at the Helmholtz Zentrum München, a partner in the German Center for Lung Research (DZL), along with colleagues from the Ludwig Maximilian University Hospital and the Max Planck Institute of Biochemistry in Martinsried.

Microscopic picture of IPF tissue

Microscopic picture of IPF tissue: Nuclei are stained in grey, smooth muscle cells in blue. The protein MZB1 (green) marks antibody producing plasma cells. Source: Helmholtz Zentrum München / Herbert Schiller

The term interstitial lung disease (ILD) encompasses a diverse range of disorders that are associated with scarring (fibrosis) of the lung tissue. Idiopathic pulmonary fibrosis (IPF) is one of them. This disease leads to the formation of excess fibrous connective tissue in the lung, thereby reducing its elasticity. It also impairs oxygen absorption and overall results in a deterioration of lung function.

“The underlying molecular mechanisms of the individual disease subtypes are not sufficiently understood and are therefore the subject of our research,” explains Dr. Herbert Schiller. Since 2015 he has led the junior research group at the Institute of Lung Biology at the Helmholtz Zentrum München, and before that he worked at the Max Planck Institute of Biochemistry (MPIB). Together with Prof. Matthias Mann’s group, which is based at MPIB, he and his team have now examined tissue samples with the aid of mass spectrometry.* 

In total, the scientists examined lung tissue obtained from 45 patients with different forms of ILD and compared them with the samples from ten healthy control subjects. In addition, they examined tissue samples of diseased and healthy areas of skin from six patients with fibrotic skin diseases.

“Interestingly, both in the lungs and skin of the fibrosis patients, we were able to identify an increased abundance of proteins specific for antibody-producing plasma cells,” explains lead author Schiller. Observations under the microscope supported these findings. This suggests that in many patients the disease could be caused by an autoimmune disorder that attacks so far unknown proteins in the lung. At present, however, there is no evidence of a causal relationship, and further studies are already initiated.

“In our study we found a high prevalence of antibody-forming plasma cells in scarred lung tissue, and the number of these cells was correlated with the reduction in the patients’ lung function,” Schiller notes. On the basis of these observations, he surmises that autoimmunity may play a bigger part in idiopathic forms of lung fibrosis than was previously assumed.

“The use of mass spectrometry to identify auto-antibodies and their antigens present in the blood of ILD patients could be the key to better diagnostic classification in the future and to potential immunotherapeutic approaches,” Schiller says. His junior research group is therefore currently engaged in developing new methods of classifying autoantibodies and in examining larger patient cohorts.

Further information

* Mass spectrometry is a technique used to analyze molecular masses. The substance to be examined is transferred into the gas phase and ionized. The ions are accelerated using an electric field and passed into a mass analyzer, where they are sorted and separated according to their mass-to-charge ratio.

“The cause of idiopathic pulmonary fibrosis (IPF), in particular, is still entirely unknown. The outlook for IPF (median survival time of 2-5 years following diagnosis) is classified as poor, and comparable to the outlook for many forms of lung cancer,” Schiller explains. Only recently two anti-fibrotic drugs – Pirfenidon and Nintedanib – have become available for the treatment of IPF. However, since antifibrotic drugs can only slow down the progression of the disease but not halt it, lung transplantation is currently the only definitive treatment for IPF.

Since October 2015, Herbert Schiller has headed the DZL junior research group “Systems Medicine of Chronic Lung Disease” at the Institute of Lung Research, Helmholtz Zentrum München. You can read more about his current research in our Portrait. The senior author of the study is Prof. Oliver Eickelberg. Until the end of last year, he was Director of the Institute of Lung Biology and Disease (ILBD), Helmholtz Zentrum München. He currently heads the Division of Pulmonary and Critical Care Medicine at the University of Colorado School of Medicine in Denver.

Christoph Mayr and Maximilian Strunz, doctoral students in Herbert Schiller’s junior research group, are members of the CPC Research School “Lung Biology and Disease” and participants in the Helmholtz Graduate School for Environmental Health (HELENA).

Original Publication:
Schiller, HB. et al. (2017): Deep proteome profiling reveals common prevalence of MZB1-positive plasma B cells in human lung and skin fibrosis. American Journal of Respiratory and Critical Care Medicine, DOI: 10.1164/rccm.201611-2263OC

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, allergies and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,500 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 19 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. 

The Comprehensive Pneumology Center (CPC) is a joint research project of the Helmholtz Zentrum München, the Ludwig-Maximilians-Universität Clinic Complex 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 a site of the Deutsches Zentrum für Lungenforschung (DZL).

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.