LONDON — Environmental and lifestyle factors, such as certain foods and infections, may trigger onset of psoriasis and account for approximately 30% of the risk of the condition in people with a genetic preposition. Research presented at the Psoriasis: From Gene to Clinic International Congress in London on Friday identified some of these factors and the mechanism involved.
“The aim of our study was to get a better understanding of the factors at the molecular level that translate the genetic predisposition for psoriasis into the actual manifestation of the disease. Essentially, why do only some of the people who have a genetic tendency towards psoriasis have it, whilst others don’t? Our results show that lifestyle factors may be important,” said Dr. Jörg Prinz, from the Ludwig-Maximilian-University of Munich.
HLA-C*06:02 is the main gene associated with risk of psoriasis, and HLA-C*06:02 positive people are between nine and 23-fold more likely to develop the condition.
In a previous study the research team from Ludwig-Maximilian-University in Munich, Germany found that HLA-C*06:02 mediates an autoimmune response against melanocytes. T-cells attack melanocytes in patients with psoriasis, and using a T cell receptor (Vα3S1/Vβ13S1) from a pathogenic T cell clone, the team identified a peptide as a melanocytic antigen. In the skin, this peptide from ADAMTS-like protein 5 is only found in melanocytes, but similar peptides are found in the environment, including in certain foods. In this latest study, the team looked at environmental factors at a molecular level to determine if they carried similar proteins that could act as a trigger for psoriasis in HLA-C*06:02 positive patients.
T cell receptors are polyspecific, they do not recognize specific antigens but react against peptides sharing a particular amino acid pattern. After defining the amino acid pattern recognized by the Vα3S1/Vβ13S1 T cell receptor, the team used a database of 56 peptides to identify those carrying the same amino acid pattern seen in melanocytes. These environmental candidates were then tested for their ability to trigger the reaction that causes psoriasis in genetically susceptible individuals.
Environmental peptides found to carry the amino acid pattern included foods such as wheat, apple, coffee and spinach; bacteria such as Chlamydia trachomatis, Mycobacterium tuberculosis and Klebsiella pneumoniae; viruses such as human cytomegalovirus; and fungi such as Trichophyton verrucosum.
“These results provide initial evidence that environmental factors may serve as potential triggers for this specific autoimmune response in psoriasis. It may also have implications in understanding how environmental factors affect the risk of autoimmune diseases in general,” Dr. Prinz said.
He added that the identification of potential triggers may help to develop strategies for psoriasis prevention in individual patients, these patients and their triggers would have to be verified in clinical practice.
Yukiyasu Arakawa, also from the Ludwig-Maximilian-University of Munich, said: “These results provide the first evidence of environmental antigens that may serve as potential triggers of the melanocyte-specific autoimmune response in psoriasis. They suggest that exposure to environmental antigens may drive priming and expansion of potentially self-reactive T cells and thus initiate autoimmune disease responses. Through the unbiased analysis of a pathogenic psoriatic T cell receptor our data furthermore may have important implications in understanding how environmental factors affect the risk for autoimmune diseases in general.”Full Article