Systemic Sclerosis (SSc)
Systemic sclerosis (SSc) is an autoimmune disease of the connective tissue. This fibrosing disease of the skin is characterized by:
- Thickening of the skin due to abnormal growth and the accumulation of collagen
- Vascular symptoms that can lead to discoloration of the hands and feet as a response to cold & painful ulcers on fingers and toes
- Deposition of calcium in lumps under the skin, often in close proximity to joints
Broadly speaking, there are two forms of the disease:
- Limited cutaneous scleroderma, located to skin on the face, hands and feet
- Diffuse cutaneous scleroderma that affects skin in general and can progress to the visceral organs, including kidney, heart, lungs and gastrointestinal tract
Systemic sclerosis disease characterization
SSc is linked to autoimmune dysfunction, although the exact trigger for disease onset is not known. The major symptoms are thought to be caused by the overproduction of collagen, which ultimately leads to endothelial damage. T-cells accumulate in the skin and secrete cytokines and other proteins that lead to the stimulation of collagen deposition. Connective tissue growth factor (CTGF) may also have a role in disease development, and CTGF gene polymorphism is frequently present in SSc patients. Another significant factor involved in the process is transforming growth factor beta (TGF-β), as it plays a crucial role in regulating the immune system.
Future diagnostic strategy
It is currently not possible to predict SSc prognosis reliably until the disease differentiates into recognizable subsets. Patients are initially diagnosed due to:
- Clinical suspicion and in some cases by biopsy
- The presence of specific anti-centromere autoantibodies (80-90% limited form of SSc, 10% diffuse SSc)
- The expression of anti-scl70 and/or anti-topoisomerase autoantibodies (30-40% diffuse SSc)
Since a reliable diagnosis of SSc can only be made after the disease has sufficiently differentiated, there is a serious unmet need for effective diagnosis and treatment, in particular for early diffuse SSc. Fortunately, our team has identified specific autoantibodies expressed by patients with SSc, providing promising novel biomarkers that may allow for earlier diagnosis and help improve patient care and treatment development.
Early diagnosis for developing better SSc treatments
Current therapies for treating SSc target several aspects of the disease following its onset, namely inflammation, autoimmunity, vascular disease, and tissue fibrosis. However, like other autoimmune diseases, patients with SSc make autoantibodies, providing a unique opportunity to accurately define patient subsets early during disease development. This information could inform drug development programs by providing new factors to target. It would also increase the chances of success during clinical trials via the co-development of CDx tests that pinpoint those patients most likely to benefit from treatment.
In order to make this approach a reality there is a need to discover and validate autoantibody signatures that correlate with SSc incidence, presentation and progression and enable insightful patient stratification. Several promising disease specific autoantigens have already been identified by our team and future collaborations with our Pharma partners will identify new opportunities for therapeutic development.