Genetic factors in autoimmune disease

The genetic make-up of the host may be a major determinant in the onset and development of autoimmune disease. Particularly relevant in this respect are those genes that control the size and type of immune response to an antigen, i.e. the MHC and antigen receptor genes.

It is well documented that organ-specific autoimmune diseases can show a familial association. However, within a family, the type of disease manifested may vary from one member to another. Recent evidence suggests that as little as a single mutation of one particular gene may switch the susceptibility for disease from one organ to another.

Several autoimmune diseases have been shown to be associated (at least loosely) with the expression of particular MHC and immunoglobulin allotypic genes. Individuals with seropositive rheumatoid arthritis (RA+) commonly express the product of the Class II gene DR4 whilst systemic lupus erythematosus (SLE) is associated with DR2 and DR3. Although these diseases are thought to be closely related, the distinct genetic association suggests that their pathology may be very different.

Modern developments in molecular biology have provided the potential for developing new types of treatment for autoimmune diseases such as gene therapy. However, further progress is required before it becomes the treatment of choice. First the genes involved in each disease must be isolated and characterised and delivery systems allowing efficient gene insertion in the target cells must be developed, as must the mechanisms to regulate expression of the introduced genes.

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