Johan Grunewald Group

The research conducted by the Respiratory Unit focuses on inflammatory disorders in the airways and lung parenchyma.

The success of much of the research is attributed to an excellent and close collaboration between experienced physicians meeting the patients and a well-equipped and closely located research laboratory with professionals, especially in the field of inflammation and immunology.

We focus our research in pulmonary medicine on inflammatory states in the airways and in the lung parenchyma.

During several decades our main interest was in Interstitial Lung Disorders, (ILD) and due to the early use of fiberoptic bronchoscopic techniques we could on site follow inflammatory and immunological reactions in disorders such as idiopathic pulmonary fibrosis, sarcoidosis, hypersensitivity pneumonitis and the pulmonary involvement in systemic diseases such as rheumatoid arthritis, myositis and multiple sclerosis. The techniques, including repeated bronchoalveolar lavage (BAL), have enabled us to study effects of exposure to environmental factors such as smoking and inhalation of particles and gases in car- and subway tunnels. We also managed to study the effects on the lungs of working in various environmental settings such as sawmills, aluminum factories and pig farms.

The BAL-techniques and much of the analytical methods of retrieved materials were developed in close collaboration between our related clinical and laboratory research units. We also have had intense cooperation with other well-renowned laboratories on local, national and international levels. These prerequisites have been most valuable also in studies of asthmatics before and after provocation with relevant allergens, in follow-up of COPD-patients and to evaluate the effects of different kinds of new therapies. The most intense and internationally recognized projects have during many years been on very well pheno- and genotyped patients with sarcoidosis. A large biobank has been created containing lots of data on different types of biological specimens collected during these studies and from healthy smokers and non-smokers as well. In combination with very good access in Sweden to different kind of registers of the citizens we have unique possibilities also for future studies pending on field of research interest.

A large number of treatment projects have been conducted in collaboration with pharmaceutical companies mostly in COPD and asthma. An intense collaboration is ongoing with epidemiologists at KI and with immunologists and specialists in genetics, proteomics and metabolomics. During the ongoing pandemic with Covid collaboration projects (parts of the SCAPIS initiative) have been initiated.

2007-2011 – Head of the KI network “Circulation and respiration” with about 540 members

Contacts are established since several years with various groups (D Moller, USA, A Fontenot USA, Joachim Muller-Querrneim Germany, M Kool The Netherlands etc)

The Heart-Lung Foundation has during a long period of time been very supportive and financed e.g. a large number of research positions, projects and travel grants. Karolinska Institutet, the Medical Research Council, FAS, the City Council of Stockholm and the National Institute of Health (NIH) and the American Thoracic Society in the US, among others, have also been highly valued financial contributors

Young investigator award at the international sarcoidosis meeting (WASOG) in L.A (1994)

The Evy and Gunnar Sandberg Prize for translational Research on Lung Diseases, (2011) (first recipient, together with Anders Eklund)

First recipient of a SLMF grant (Svensk Lungmedicinsk Förening), 225 tkr (2015)

Supervisor for 30 graduated PhD-students; as main supervisor (n=13): J Wahlström 1999, A Planck 2002, K Katchar 2003, F Sabounchi-Shütt 2004, M Müller 2006, F Idali 2008, E Silva 2011, P Darlington 2013, H Haugom Olsen 2015, Marianne Sundberg Kövamees 2017, Y Kaiser 2018. M Abo Al Hayja 2020 and Emil Wiklundh 2021. Acted as external examiner for PhD students in Norway, Denmark, England, The Netherlands.

We recently identified a new candidate (Aspergillus Nidulans) as a possible antigen of involved in the inflammatory reaction in sarcoidosis (J EXP MED 2021).

CD4+ T cells in the lungs of acute sarcoidosis patients recognize an Aspergillus nidulans epitope. Greaves SA, Ravindran A, Santos RG, Chen L, Falta MT, Wang Y, Mitchell AM, Atif SM, Mack DG, Tinega AN, Maier LA, Dai S, Pinilla C, Grunewald J†, and Fontenot AP†.  J Exp Med. 2021 Oct 4; doi: 10.1084/jem.20210785.

Challenges of Sarcoidosis and Its Management. Drent M, Crouser E and Grunewald J. N Engl J Med. 2021 Sep 9; doi: 10.1056/. Review

Sarcoidosis. Grunewald J, Grutters J, Arkema E, Saketkoo LA, Moller D and Müller- Quernheim J.  Nat Rev Dis Primers. 2019 Jul 4;5(1):45. doi: 10.1038/s41572-019-0096-x. Review.

High-density Genetic Mapping Identifies New Susceptibility Variants in Sarcoidosis Phenotypes and Shows Genomic-driven Phenotypic Differences. Rivera NV, Ronninger M, Shchetynsky K, Franke A, Nöthen MM, Müller-Quernheim J, Schreiber S, Adrianto I, Karakaya B, van Moorsel CH, Navratilova Z, Kolek V, Rybicki BA, Iannuzzi MC, Petrek M, Grutters JC, Montgomery C, Fischer A, Eklund A, Padyukov L, and Grunewald J.  Am J Respir Crit Care Med 2016 (193(9):1008-1022

Proteomic profiling reveals five autoimmune targets in sarcoidosis. Häggmark A, Hamsten C, Wiklundh E, Grönlund H, Schwenk J, Eklund A, Grunewald J* and Nilsson P* (*shared senior authors). Am J Respir Crit Care Med. 2015, 191(5):574-583

Löfgren´s syndrome: HLA strongly influence the disease course. Grunewald J and Eklund A. Am J Respir Crit Care Med. 2009, 179:307–312

Sex specific manifestations of Löfgren´s syndrome. Grunewald J and Eklund A. Am J Respir Crit Care Med 2007, 175:40-44

A new model for an etiology of RA; Smoking may trigger HLA-DR (SE) restricted immune reactions to autoantigens modified by citrullination. Klareskog L, Stolt P, Lundberg K, Källberg H, Silva C, Grunewald J, Rönnelid J, Ulfgren A-K, Harris H, Rantapää-Dahlqvist S, Eklund A, Padyukov L, Alfredsson L and the EIRA study group. Arthritis Rheum 2006, 54(1):38-4

Lung T helper cells expressing TCR AV2S3 associate with clinical features of pulmonary sarcoidosis. Grunewald J, Berlin M, Olerup O, Eklund A. Am J Respir Crit Care Med 2000, 161:814-818

HLA-DR predicts the prognosis in Scandinavian patients with pulmonary sarcoidosis. Berlin M, Fogdell A, Olerup O, Eklund A and Grunewald J. Am J Respir Crit Care Med. 1997, 156:1601-1605