Introduction

Coeliac disease (CD) is a disease of the small intestine characterised by the development of villous atrophy, in response to ingestion of dietary proteins contained in wheat, barley and rye (Kelly et al., 1990). Villous atrophy, in turn, results in malabsorption of essential nutrients with the development of steatorrhea, weight loss and specific deficiency syndromes. Villous atrophy is associated with a cellular infiltrate comprising increased intra-epithelial lymphocytes, increased lamina propria lymphocytes and plasma cells (Anand et al., 1981; Fry et al., 1972; Ferguson,1987; Lancaster–Smith, Kumar & Dawson, 1975). Coeliac disease is tightly linked genetically to genes encoded in the major histocompatibility complex (MHC). In this respect it is similar to the auto-immune diseases of thyroid, pancreas and joints. However, since the precipitating agent is known, coeliac disease may serve as a useful model for auto-immune disease in the human if the interactions between genetic and environmental factors can be adequately defined. In this respect, an understanding of the genetic basis of coeliac disease is essential for an understanding of the immune hypotheses of the disease.

Genetic studies of coeliac disease

Coeliac disease shows a geographical predeliction, with a particularly high incidence in Northern Europe. There is a clear familial predisposition to the disease (Myllotte et al., 1974), but this does not follow classical Mendelian patterns, suggesting the possibility of multigenic and/or multifactorial aetiopathogenesis. Concordance in monozygotic twins occurs in approximately 75% of cases (Walker–Smith, 1973).