Mechanisms causing psoriasis and other autoimmune diseases
The project focuses on the identification of the mechanisms causing inflammatory reactions in psoriasis and other autoimmune diseases. The aim is to find the triggering autoantigen, how it is formed, and thereby to develop specific treatment strategies.
The research builds on some important observations:
- Epidemiological research using family- and twin studies indicates that both hereditary and environmental factors are of significance for the development of autoimmune diseases.
- The fact that no infectious agents causing the inflammatory reaction has been identified, leads to the assumption that there is an innate antigen.
- The fact that autoimmune diseases are associated with certain types of tissue indicates that specific antigens are involved.
- The fact that inflammatory reactions are confined indicates a local production of an antigen.
- The fact that the affected organ or organ-system is only partially attacked indicates that the antigen involved is not specific to the affected organ.
- The chronic nature of the inflammatory reaction indicates a positive feedback mechanism, meaning that the inflammatory reaction contributes to its own maintenance.
- The increased prevalence of various autoimmune diseases in the same person may indicate the involvement of a common antigen.
Psoriasis and Pso p27
Our research has focused on psoriasis and the identification of the autoantigen Pso p27, which we have found in the affected skin of patients with psoriasis. We have shown that the protein is immunologically active and forms immune complexes which contribute to the inflammatory reaction.
On improvements in the disease activity, the production of Pso p27 also stops.
Pso p27 is produced in mast-cells through the transformation of proteins known as SCCA-molecules. The SCCA molecules are split by the mast-cell enzyme chymase into Pso p27 and two split products. The split products form a complex with Pso p27, and this complex is structurally and functionally different from the mother molecule.
The transformation of SCCA molecules to the Pso p27 complex is probably central in the disease process and will therefore be a potential target for targeted treatment.
Pso p27 and other autoimmune diseases
The autoantigen Pso p27 has also been identified in sick organs with other autoimmune diseases such as chronic inflammatory bowel disease, arthritis, ankylosing spondylitis (AS) and sarcoidosis. This indicates that the mechanism for these diseases could be the same as for psoriasis and that treatment strategies for different autoimmune diseases could be similar. We aim to understand the underlying mechanisms for other autoimmune diseases in parallel with the research into psoriasis.
1. Mechanisms regulating the production and function of Pso p27. We have shown that Pso p27 is transformed from SCCA-molecules and appear as Pso p27 complexes that are structurally different from the SCCA molecules. We wish to study whether the transformation of Pso p27 aggregates could play a role in the disease process.
2. Expression of SCCA in psoriasis lesions. The transformation of SCCA molecules to Pso p27 occurs in mast-cells in psoriasis lesions. Concerning treatment strategies, it will be important to establish whether SCCA molecules are synthesised in – or are taken up by the mast-cells.
3. Biological effects of Pso p27. We investigate to what degree Pso p27 induces the production of pro-inflammatory factors.
4. Pso p27 in other skin diseases. We will investigate whether Pso p27 is involved in other skin diseases than psoriasis.
5. The effect of Chinese herbs on the formation of Pso p27. We study whether extracts from Chinese herbs have an inhibiting effect on the formation of Pso p27 complex from SCCA1