Asthmatics show DNA changes in immune cells

Children with asthma have epigenetic DNA changes in certain cells of their immune system, a major international study involving researchers at the Institute of Environmental Medicine (IMM) shows. The finding, which is presented in The Lancet Respiratory Medicine, can one day lead to improved diagnostics and treatment.

Asthma is a respiratory disease caused by a chronic inflammation of the airways. An estimated 800,000 people have asthma in Sweden, about 50,000 of whom suffer so seriously that their everyday functioning is impaired. It is thought that asthma is caused by a combination of hereditary and environmental factors, but there are still many knowledge gaps to be filled.

Collaborating with Groningen University in the Netherlands amongst other institutes, researchers at IMM have conducted an extensive study of the epigenetic changes that can be related to asthma. Epigenetics governs where and when different genes are active and DNA methylation is one of its most common regulatory mechanisms. The present study shows that asthmatics have a lower degree of DNA methylation in certain immune cells than healthy controls, particularly in what are known as eosinophils, which play a critical part in the asthmatic inflammation. The researchers identified DNA changes in 14 gene regions linked to children’s asthma, but these changes were not present at birth.

Key to understanding disease mechanisms

“We believe that our findings are key to understanding the disease mechanisms, even if we’ve not yet been able to show that the epigenetic changes actually cause asthma,” says Erik Melén, docent at the Institute of Environmental Medicine, Karolinska Institutet. “Our results suggest that the lower DNA methylation in asthmatics increases activation of the immune cells, which play a central part in the development of asthma.”

The study included over 5,000 children from 10 European cohorts, including the Swedish birth cohort BAMSE, which is led by Erik Melén. The research is the result of a longer-standing collaboration with European researchers in the EU MeDALL (Mechanisms of the Development of Allergy) programme.

“This is the largest epigenetic asthma study to date and we hope that our discoveries will give rise to better diagnostics and treatment possibilities,” says Dr Melén. “Influencing epigenetic regulation could be a new and interesting therapeutic strategy.”

The study was financed by the EU (MeDALL), Formas (the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning), the Swedish Heart-Lung Foundation (the Prince Daniel Grant for Promising Young Researchers), the Swedish Foundation for Strategic Research, Stockholm County Council (ALF funding), the Strategic Research Area in Epidemiology at Karolinska Institutet and the Swedish Research Council.

Publication

DNA methylation in childhood asthma: an epigenome-wide meta-analysis
Cheng-Jian Xu, Cilla Söderhäll, Mariona Bustamante, Nour Baïz, Olena Gruzieva, Ulrike Gehring, Dan Mason, Leda Chatzi, Mikel Basterrechea, Sabrina Llop, Maties Torrent, Francesco Forastiere, Maria Pia Fantini, Karin C. Lødrup Carlsen, Tari Haahtela, Andréanne Morin, Marjan Kerkhof, Simon Kebede Merid, Bianca van Rijkom, Soesma A Jankipersadsing, Marc Jan Bonder, Stephane Ballereau, Cornelis J Vermeulen, Raul Aguirre-Gamboa, Prof Johan C de Jongste, Henriette A Smit, Ashish Kumar, Göran Pershagen, Stefano Guerra, Judith Garcia-Aymerich, Dario Greco, Lovisa Reinius, Rosemary RC McEachan, Raf Azad, Vegard Hovland, Petter Mowinckel, Harri Alenius, Nanna Fyhrquist, Nathanaël Lemonnier, Johann Pellet, Charles Auffray, Pieter van der Vlies, Cleo C van Diemen, Yang Li, Cisca Wijmenga, Mihai G. Netea, Miriam F. Moffatt, William O.C.M Cookson, Josep M. Anto, Jean Bousquet, Tiina Laatikainen, Catherine Laprise, Kai-Håkon Carlsen, Davide Gori, Daniela Porta, Carmen Iñiguez, Jose Ramon Bilbao, Manolis Kogevinas, John Wright, Bert Brunekreef, Juha Kere, Martijn C Nawijn, Isabella Annesi-Maesano, Jordi Sunyer, Erik Melén, Gerard H Koppelman
The Lancet Respiratory Medicine, online 23 February 2018