MHH physician Dr Stephan Traidl is investigating the effects of systemic therapies for atopic dermatitis. The Else Kröner Fresenius Foundation honours him with the Memorial Scholarship worth 250,000 euros.
Dr Stephan Traidl investigates the effect of systematic therapies for atopic dermatitis. Copyright: Karin Kaiser / MHH
Unbearable itching and dry, flaky skin are among the typical signs of atopic dermatitis. It is one of the most common chronic inflammatory skin diseases. In Germany, up to 2.5 million people are affected every year, of which around 1.3 million are children and adolescents.
The disease usually begins in infancy or early childhood and progresses in episodes. Atopic dermatitis is technically known as atopic dermatitis (AD). Atopic dermatitis is characterised by a genetic hypersensitivity to various, usually harmless, substances in the environment. The overactive immune system reacts with inflammation in order to fight the supposed attackers. The skin barrier is also impaired in atopic dermatitis and therefore also its protective function against pathogens. Those affected are therefore susceptible to bacterial infections with Staphylococcus aureus and severe infections with the herpes simplex virus.
In recent years, various drugs have been approved for treatment, which are intended to combat the causes from within and target the misdirected immune response. However, the extent to which these systematic therapies bring about long-term improvement has not yet been comprehensively investigated. Dr Stephan Traidl, assistant physician at the Clinic for Dermatology, Allergology and Venereology at Hannover Medical School (MHH), now wants to investigate this question. The Else Kröner-Fresenius Foundation has awarded the scientist the Memorial Scholarship for particularly talented young doctors and is funding his project ‘Sustainable influence on atopic dermatitis with systemic therapies’ with 250,000 euros over two years.
Stopping the inflammatory reaction
Type 2 immune cells play a central role in atopic dermatitis. Their actual function is to defend against parasites and they also help to repair damaged tissue. The resulting autoimmune inflammatory reaction is treated with various biotechnologically produced drugs and anti-inflammatory agents that are particularly directed against this type 2 immune response. These include so-called Janus kinase (JAK) inhibitors. They prevent the JAK enzymes inside the cell from transmitting the signals of pro-inflammatory messenger substances from the cytokine group. ‘The fundamental question is whether a targeted therapy can influence atopic dermatitis in the long term and have a positive effect on its progression,’ says Dr Traidl.
To answer this question, the physician is looking at clinical data from the atopic dermatitis register TREATgermany. On the other hand, he relies on omics data sets that provide information about the transcriptome of the patients, i.e. which genes that are important for the disease are actually read and converted in them. These data sets are many orders of magnitude larger than the clinical data, and analysing them is correspondingly labour-intensive. However, this is no problem for Dr Traidl, who studied data science at the MHH alongside his medical studies. Skin biopsies from patients are also analysed with the help of spatial transcriptomics. This technique provides a comprehensive overview of transcriptional activity in intact tissue sections. The molecular biological processes identified in atopic dermatitis can thus be assigned to specific structures in the skin and the various mechanisms of action of the drugs can also be investigated.
Preventing further autoimmune diseases
‘I want to look at how the clinical and omics data changes during the therapy and what happens when the therapy is discontinued,’ he explains. Dr Traidl is investigating the question of whether, depending on the therapy, different permanent inflammation patterns can be found in the skin, which can promote a flare-up of the disease after the medication is discontinued. Or whether there may be endogenous substances that prevent precisely this. Another aspect is the risk for atopic dermatitis sufferers of developing other atopic diseases such as allergic asthma, allergic rhinitis or food allergies. The doctor also wants to investigate whether such an ‘atopic march’ can be prevented in children and adolescents with the help of systematic therapies. The chances of this are not bad.
‘If the patient's excessive immune response is curbed, there will certainly be fewer inflammatory reactions in the skin.’ This may also reduce the risk of patients becoming sensitised to other allergenic substances that trigger a new autoimmune reaction.
Text: Kirsten Pötzke