Research focus of the Clinic for Rheumatology
Our focus lies on the following priority diseases: systemic sclerosis, rheumatoid arthritis, spondyloarthritis/psoriatic arthritis, vasculitis, mixed connective tissue disease (MCTD), Sjögren’s syndrome. At the Balgrist campus, the focus areas are Complex Regional Pain Syndrome (CRPS) and Chronic Back Pain (Modic Changes).
Systemic sclerosis
Systemic sclerosis is a multisystem autoimmune fibrotic disease We are using this disease as a model to understand the mechanisms of fibrosis in skin and lung disease. We are also interested in vasculopathy contributing to fibrosis in systemic sclerosis. Our special interest is on non-coding RNA, including microRNA and long non-coding RNA. We are using 2D and 3D cultures, as well as animal models to understand and characterise mechanisms of fibrosis. Our overall aim is to develop new therapies for fibrotic diseases.
Rheumatoid arthritis
Rheumatoid arthritis is a chronic systemic inflammatory disease that mainly affects the joints. It occurs in about 1% of the population and is most common between the ages of 40 and 60. Women are affected three times as often as men. The causes of the disease are unknown. Genetic and environmental factors (especially smoking) contribute to the development of the disease. The immune system is activated and triggers inflammation in the joints (synovitis). If left untreated, this inflammation leads to destruction of the joints and subsequently to functional impairment. Various immunosuppressants are available for the treatment of rheumatoid arthritis, which in most cases can suppress the inflammation and stop the joint damage. However, in around a third of patients, these medications do not work or lose their effect over time. In order to find better treatment options or even prevent the development of the disease, further research into the triggering mechanisms is required.
Spondyloarthritis/psoriatic arthritis
The spondyloarthritides encompass a group of inflammatory rheumatic diseases that affect the axial skeleton (spine and sacroiliac joints), peripheral joints, and entheses. Genetic factors, such as the association with the HLA-B27 antigen, and environmental factors play a role in the development of these diseases, whether they are axial or predominantly peripheral spondyloarthritides. Uncontrolled repair processes after inflammation subsides can lead to increased osteogenesis and osteoproliferation. As the disease progresses, function and mobility can be significantly impaired.
Psoriatic arthritis is a form of spondyloarthritis and affects 20-30% of individuals with psoriasis. The range of manifestations includes peripheral arthritis, dactylitis, and enthesitis. In a significant proportion of patients, there is also inflammatory involvement of the spine and sacroiliac joints. Collaboration with dermatologists is crucial for effective treatment of this disease.
Rheumatoid arthritis is a chronic systemic inflammatory disease that mainly affects the joints. It affects around 1% of the population, with the highest incidence between the ages of 40 and 60. Women are affected three times more often than men. The exact causes of the disease are not yet known, but both genetic and environmental factors, particularly smoking, contribute to its development. The activated immune system triggers inflammation in the joints (synovitis). If left untreated, this inflammation can lead to joint destruction and functional impairment.
The research groups of Adrian Ciurea and Raphael Micheroli work intensively together in the entire field of inflammatory joint diseases.
Vasculitis
Vasculitides are diseases with chronic inflammation of blood vessels of various sizes, which in many patients require long-term immunosuppressive therapy to prevent severe irreversible organ damage or even organ failure. The clinical symptoms differ depending on which vascular areas and organs are affected. As all tissues in the body are supplied with nutrients and oxygen via blood vessels, many different tissues can be affected and damaged, from internal organs such as the lungs or kidneys to the nervous system, skin and eyes.
Mixed connective tissue diseases
Systemic rheumatic diseases such as systemic sclerosis (SSc), Sjögren’s syndrome (SjD) and Ehlers-Danlos syndrome (EDS)/hypermobility syndrome (HSD) are complex diseases that affect multiple organ systems. In SSc, fibrosis of the skin and internal organs, especially the lungs, can lead to severe complications such as interstitial lung disease (ILD) and pulmonary hypertension (PH). SjD primarily affects the exocrine glands and causes the typical symptoms of dry eyes and dry mouth, but can also affect other organs such as the lungs, kidneys and nervous system, with an increased risk of lymphoma in severe cases. EDS, which is characterized by connective tissue abnormalities, often leads to joint hypermobility, skin fragility and vascular complications.
Metabolic regulation of inflammation
Metabolic pathways play a decisive role beyond energy production and serve as important regulators of immune cell function. They influence how immune cells develop, activate, differentiate and react to stimuli. Dysregulation of immune cell metabolism can disrupt immune homeostasis and contribute to chronic inflammation, loss of self-tolerance and the onset or progression of autoimmune diseases. A better understanding of these metabolic disorders has the potential to reveal how metabolic imbalances promote autoimmunity and to identify new therapeutic strategies for the treatment of autoimmune diseases.
Pain in the lower back
The ‘Global Burden of Disease Study’ identified low back pain (LBP) as the world’s most disabling condition. Vertebral bone marrow lesions – named Modic changes – coincide with LBP. Modic changes are highly prevalent in LBP patients yet a poorly understood degenerative spinal disorder. Patients with Modic changes cannot be treated adequately, first because they cannot be identified in primary-care due to the lack of diagnostic tools, and second because there are no targeted treatments available for Modic changes.
CRPS
Complex regional pain syndrome (CRPS) is a condition of extreme pain affecting a part of the body with clinical features including chronic inflammation, sensory and motor dysfunctions and changes to skin and bones. Symptoms usually appear after trauma or surgery. Current therapies are mostly symptomatic and do not intervene with the underlying disease mechanisms.
Biomedical data science
As many molecular biology labs and clinical research groups leverage modern AI systems in their workflows, we need tools that quantify their uncertainty to uphold scientific standards. In the past, we relied on statistical uncertainty quantification in the form of p-values and confidence intervals. Almost every paper reported those quantities and allowed us to judge the credibility of a research discovery. his common statistical language—although not without its critics—allowed us to focus our resources towards the most promising discoveries. How can we quantify our level of surprise of a discovery with modern prediction models in a similar fashion? This is a typical question that Biomedical Data Science tries to tackle by leveraging ideas from Statistics and Computer Science.
