A German-Serbian research project led by DZL scientist Dr. Stefan Hadzic is investigating how altered proteins contribute to COPD severity and progression – and how the resulting misguided immune response could be selectively blocked.
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of illness and premature death worldwide. Current treatments can alleviate symptoms and reduce exacerbations, but they cannot yet stop the progressive destruction of lung tissue. Even after smoking cessation, the disease can continue to progress. The reasons for this are not yet fully understood.
This is where the new German-Serbian research project “Protein nitration-induced autoimmunity as a driver of COPD severity and progression” (AIMCOPD) comes in. Led by Dr. Stefan Hadzic, a lung specialist at the Cardio-Pulmonary Institute (CPI) at Justus Liebig University Giessen and Principal Investigator in the German Center for Lung Research (DZL), and Dr. Dragica Micanovic from the Institute for Biological Research “Siniša Stanković” (IBISS) at the University of Belgrade, the team is investigating a potentially underestimated mechanism: an immune response directed against the body’s own lung tissue.
Cigarette smoke and air pollutants expose lung tissue to considerable chemical stress. As a result, proteins in the lungs can undergo chemical modifications. One such modification is nitration, which can affect the amino acid tyrosine. Previous work by the research team suggests that nitrated proteins may play an important role in COPD: the greater the amount of these altered proteins detected in lung tissue, the more severe the disease may be.
The researchers suspect that the immune system may recognize some of these altered proteins as foreign. It could then produce autoantibodies against so-called neoepitopes, triggering an immune response against the body’s own lung tissue. This response could persist even after the original trigger, such as cigarette smoke, has been removed. Such sustained immune activation could in turn promote lung tissue destruction and impair the lung’s ability to repair itself.
Over the next three years, the researchers will systematically investigate which nitrated proteins and 3-nitrotyrosine (3-NT) neoepitopes trigger an immune response in COPD. Among other approaches, they will develop a comprehensive 3-NT proteome atlas. Advanced methods such as mass spectrometry and immunopeptidomics will help identify disease-relevant protein modifications and immune responses.
In parallel, a well-characterized COPD patient cohort will be established in Serbia. This cohort will serve as an independent validation cohort and, in the long term, enable cross-border research. Clinical data will also be linked to information on autoantibodies and disease progression.
Based on these findings, the researchers aim to identify those autoantibodies that actually contribute to COPD pathology. They will then develop strategies to selectively block this misguided immune response. A particular focus will be on neutralizing antibodies designed to specifically target disease-relevant structures without suppressing the immune system as a whole.
The approaches will initially be investigated in preclinical and ex vivo models. In the long term, this work could lead to a new diagnostic or therapeutic strategy that goes beyond treating COPD symptoms and instead targets mechanisms driving disease progression.
The project brings together the expertise of the Cardio-Pulmonary Institute at Justus Liebig University Giessen and the immunological research of the Institute for Biological Research “Siniša Stanković” in Belgrade. At the same time, the collaboration aims to sustainably strengthen lung research in the Western Balkan countries. In Belgrade, a new junior research group and modern equipment for lung function testing will be established, among other activities. Scientific exchanges between the participating institutions will also support the training of the next generation of researchers.
AIMCOPD is funded by the German Federal Ministry of Research, Technology and Space (BMFTR) as part of the “Funding of Projects between Germany and the Western Balkan Countries” (WEB2025) programme, with more than €350,000. The project runs from 1 October 2026 to 30 September 2029.
Project partners:
Justus Liebig University Giessen, Cardio-Pulmonary Institute (CPI), Germany
Institute for Biological Research “Siniša Stanković” (IBISS), University of Belgrade, Serbia
Project coordinators: Dr. Stefan Hadzic (JLU Giessen) and Dr. Dragica Micanovic (IBISS Belgrade)
Funding reference: 01DS26011
