The immune system

What happens in psoriasis and psoriatic arthritis?

There are three main pieces of evidence which suggest the immune system is involved in psoriasis. Genes and the immune system go together, working alongside each other all playing a part in the master plan of our bodies.

What is the immune system?

Your immune system is designed to protect you against disease. It is made up of a number of white blood cells (T cells) that patrol the body in search of cells and proteins that should not be there. All your cells have special identity tags to help your immune system recognise them. Sometimes, however, the immune system over-reacts or even attacks parts of the body to cause problems.

The term tissue type refers to a collection of markers on the surface of the cells in our bodies. These markers contribute to distinguishing one person from another are used by the immune system as identity tags. The directions for the production of these markers are found in the genes of the major histocompatibility complex (MHC) which are passed from one generation to the next and are, therefore shared within families.

At present, the search is on for a gene or collection of genes in the MHC which are associated with psoriatic arthritis (PsA). Other rheumatic diseases such as rheumatoid arthritis and ankylosing spondylitis occur more frequently in individuals with particular MHC genes.

It is thought that there is a genetic predisposition to the development of psoriasis and psoriatic arthritis but exactly which genes are involved is unknown at present. Evidence suggests that inflammation in the skin and joints is in part directed and maintained by cells of the immune system called T lymphocytes. Under normal circumstances these cells survey the bloodstream and body tissues for signs of infection and cancer.

In the event that a foreign agent, such as a virus, is found, T lymphocytes destroy the infected cells and send messages into the local area to recruit assistance in clearing the infection. For reasons unknown, T lymphocytes are present in large numbers in the psoriatic skin and inflamed joints of people with PsA. The activity of these T lymphocytes and the messages which they produce contribute to the thickened epidermis in psoriasis and damage in the joint. Many of the stronger drugs prescribed for PsA such as methotrexate, azathioprine and steroids serve to reduce the production and/or activity of the cells of the Immune system, including T lymphocytes.

It is through tissue type markers, the products of MHC genes, that T lymphocytes communicate with the rest of the body. These markers are required for a T lymphocyte to receive information as to the identity and state of healthiness of body tissues. If a particular tissue type were found to be linked to the development of PsA it would provide essential information regarding the seemingly inappropriate activity of T lymphocytes.

It has been suggested for other diseases linked to certain tissue types that the affected tissue is altered such that the immune system mistakes it for something foreign. Alternatively, an unidentified infection may result in chronic inflammation either because it resides in inflamed tissue or causes confusion in immune cells resulting in healthy tissue being mistaken for infected tissue.

Genetic and immune system

There is a collection of genes which code for the identity tags in the immune system. The way your immune system behaves is controlled by the genes you have inherited. Each gene acts in a different way. Some diseases like psoriasis or rheumatoid arthritis affect certain people with certain identity tags.

The way your immune cells and skin cells act towards each other in psoriasis seems to change:

• Large numbers of white blood cells (T cells) move into the skin
• Levels of immune proteins in the skin change - some increase and others decrease

Lesional tissue

Inflamed skin and joints show similar characteristics. The tissue is invaded by T cells (from white blood cells) and other immune cells from the bloodstream. This activity causes cells in the top layer of the skin to divide too quickly. These cells also contribute to the damage which occurs to joints in arthritis. Scientists do not know exactly why this is happening, but controlling the disease seems to depend on controlling these cells.

Therapy

Many of the most potent therapies used to control psoriasis damage the action of immune cells. The drugs attack a wide variety of cells, good and bad.

As more is learned about how immune activity contributes to psoriasis, new therapies will be developed which are more specific.

If we can manipulate immune responses more selectively, this could be key to the management of psoriasis. These treatments are not widely available at present.