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.

The autoantigen Pso p27 is expressed in psoriasis lesions (left), but not in healthy skin (right)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.

Both SCCA (left) and Pso p27 (right) are present in Mast Cells in psoriatic lesions

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.

On-going projects:

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.

Project members: Lars Hagen, Geir Slupphaug, Hilde Lysvand and Ole-Jan Iversen.

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.

Project members: Hilde Lysvand and Ole-Jan Iversen

3. Biological effects of Pso p27. We investigate to what degree Pso p27 induces the production of pro-inflammatory factors.

Project members: Liv Ryan, Terje Espevik, Hilde Lysvand and Ole-Jan Iversen.

4. Pso p27 in other skin diseases. We will investigate whether Pso p27 is involved in other skin diseases than psoriasis.

Project members: Henrik Richter Hammeren, Brita Solveig Pukstad, Hilde Lysvand and Ole-Jan Iversen.

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

Project members: Wang Junhui, Yan Yehe, Liu Wali, Hilde Lysvand and Ole-Jan Iversen. 

Wed, 01 Jul 2015 20:17:16 +0200

Crystal structure of Pso p27 complex.


Professor Ole-Jan Iversen