Integration of the detailed analysis of immune processes in (neuro)inflammatory diseases
The multidimensional analysis of MS immune cells using flow cytometry has revealed that MS has four different immunological endophenotypes, i.e. neurobiological disease correlates. They are stable over time and influenced by genes. Two of these immune signatures in particular - the inflammatory and the degenerative type - are associated with specific clinical characteristics. Immunotherapies work differently for each of these forms. Based on this groundbreaking finding, we at the URTC want to identify disease-specific endophenotypes in a number of inflammatory diseases. In addition, scores for predicting the course of the disease are to be developed and validated. Data already collected in the pilot phase, as well as data from ongoing projects and cohorts, will be used for this purpose.
This approach should (1) provide comprehensive insights into the specific immunobiology underlying very different neurological and neuropsychiatric diseases. These range from neuroinflammatory diseases such as neuromyelitis optica, Susac syndrome, autoimmune encephalitis and myasthenia gravis to organ-specific autoimmune diseases such as rheumatoid arthritis and psoriasis and psychiatric diagnoses in which a change in the peripheral immune signature is known, such as affective disorders. The aim is (2) to find out whether a specific immune signature during treatment helps to predict treatment success. Finally, (3) the research approach should be adapted so that the investigations can be more easily integrated into clinical routine.
Role of inflammatory mechanisms in the context of progression and regeneration
When do reparatory mechanisms succeed? When do they fail? We would like to better understand the factors that determine progression and regeneration in cronic inflammatory disorders. Therefore wwe characterize successful comared to failed reparatory mechanisms in different tissues/organs. This translational approach allows us to identify organ-specific as well as cross-organ mechanisms influencing tissue repair.
Environmental and lifestyle changes (as opposed to genetics) in the context of autoimmune pathophysiology
Many autoimmune diseases presumably develop from an interplay of genetic and environmental factors. Twin studies are particularly suitable for finding out which of the two factors plays which role. In the pilot phase, we have already been able to discover a specific population of inflammatory CD4+ cells that occurs in the preliminary stage of MS. The consolidation phase that is now underway should clarify this: How do environmental factors influence the emergence and further development of autoimmunity in the CNS? And how can these factors be influenced by targeted therapeutic measures? Two important environmental factors are conjugated linoleic acid (CLA) and UV light. Both have a proven effect on the immune system. At the URTC, we are now planning a phase II clinical trial to investigate the effect of CLA and probiotics as an adjunct to immunotherapy in patients with relapsing-remitting MS.
n recent years, another environmental factor has also become the focus of scientific interest: cell metabolism. Studies have shown that the metabolism of healthy and diseased immune cells is different, which in turn can shed light on the mechanisms of autoimmunity. This highly topical subject is now being investigated more intensively at the URTC Neuroinflammation.
Prediction of disease progression in affective disorders by combined analysis of imaging features and immune signatures
Major depressive disorder (MDD) is just as much a part of this as bipolar disorder (BD) - formerly known as ‘manic’ depression: We are talking about affective disorders (AD). They affect almost one in ten people in Germany and are associated with a high level of individual suffering. Although a relatively large number of people are affected, sometimes severely, the mechanisms and factors that influence the long-term course of the disease are still poorly understood. The Collaborative Research Centre TRR 393 ,Trajectories of affective disorders: Cognitive-emotional mechanisms of symptom changes’, founded in October 2024, aims to remedy this deficit. Researchers from Marburg and Münster want to
- determine the course of relapses and remissions in AD,
- determine cognitive-emotional mechanisms and neurobiologicals correlates of acute symptom changes, and
- investigate interventions based on disease-mechanisms.
The project is initially being funded by the German Research Foundation until the end of 2028.
Preliminary work at the UFBZ has laid the foundations for this major project. In order to analyse the longitudinal course of affective disorders, we at the URTC look at changes in brain structure, immune signatures and environmental influences over long periods of time. With the help of machine learning and integrated neuroimaging and immunological analyses, we were able to show that when affective disorders occur more frequently they are associated with greater grey matter volume loss. Risk factors such as childhood maltreatment can also influence the course of the disease by affecting the cortical structure. In the DFG-funded Reseach Group „Neurobiology of affective disorders“ (FOR 2107) we combine long-term imaging data with that of immunologic analyses to predict disease course.
To implement these projects, some of the organisations involved have been working together on an interdisciplinary basis for more than a decade. During this time, valuable resources have been created:
- Detailed characterisation of samples from thousands of patients, which depict all aspects of CNS inflammation and also make the course of the disease visible at a molecular level,
- An infrastructure for conducting clinical trials at all stages, which was partially established together with the Medical Faculty of Muenster (Early Clinical Trial Unit)
- The knowledge and methods to analyse various biological compartments and make them usable for studies
- A working group on stem cell technologies funded by the UFBZ (working group leader Yotam Menuchin-Lasowski). The methods used there allow interactions between different cell types - such as neurones, glia and peripheral immune cells - to be visualised. This means that inflammatory processes in the central nervous system can be analysed more precisely than ever before.
- Close collaboration with experts in the field of artificial intelligence and computational biology to analyse large multimodal data sets
- a endowed junior professorship (W1) for systems biology in neuroinflammatory diseases (Prof Christian Thomas)
