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Twin studies in auto-immune disease.

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Department of Diabetes and Metabolism, St. Bartholomew's Hospital, London, UK.


Immune-mediated diseases affect up to 5% of the population and are a major cause of morbidity and mortality. These diseases can be organ specific, such as insulin-dependent diabetes (IDDM) and non-organ specific, such as Rheumatoid Arthritis (RA). Identical and non-identical twins have been used to establish whether these diseases are determined by genetic or environmental factors. The results of these studies have been collated in a new section of the Mendel Institute in Rome. Diseases included in these studies included IDDM, RA, Systemic Lupus Erythematosus (SLE), Multiple Sclerosis (MS) and Myasthenia. Striking differences in concordance rates between identical and non-identical twins in all these studies suggest that genetic factors are important in causing these diseases. All the diseases are known to be associated with HLA genes on chromosome 6 which may account for some or all of the genetic susceptibility. However, in the majority of pairs the affected twin has an unaffected co-twin. These observations suggest that non-genetically determined factors, probably environmental factors and not somatic mutations, are critical. The study of unaffected co-twins, who are at high disease-risk, has allowed the identification of changes which precede and predict the clinical disease. The immune-mediated destruction in many of these diseases is probably caused by T-lymphocytes. Twin studies have shown the importance of genetic factors in determining T-cell responses. Identical twins should, therefore, provide the perfect test bed to assess the role of T-cells in immune-mediated diseases.

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