Finnish Red Cross Blood Transfusion Service and Faculty of Science, Department of Biosciences, Division of Genetics, University of Helsinki, Finland Dissecting Genetic Susceptibility to Gluten Sensitivity: Hla-linked Risk Factors in Coeliac Disease and Dermatitis Herpetiformis

................................................................................................... 7 REVIEW OF THE LITERATURE ...................................................................... 9 Human Immunology and HLA ....................................................................... 9 Intestinal mucosal immunology ......................................................................... 9 Human leucocyte antigen, HLA ....................................................................... 10 Disease associations........................................................................................ 17 Genetics of multifactorial (‘complex’) diseases ........................................... 18 Complex diseases ............................................................................................ 18 Genetic studies ................................................................................................ 19 Coeliac disease, gluten sensitive enteropathy ............................................ 23 Clinical picture .................................................................................................. 23 Diagnosis .......................................................................................................... 25 Prevalence ........................................................................................................ 25 Dermatitis herpetiformis ................................................................................... 26 Pathogenesis .................................................................................................... 27 Genetics ........................................................................................................... 29 Finnish studies on coeliac disease .................................................................. 32 AIMS OF THE STUDIES............................................................................... 34 STUDY SUBJECTS AND ETHICAL PERMISSIONS ...................................... 35 Coeliac disease patients ............................................................................. 35 Multiplex families .............................................................................................. 35 Simplex families ................................................................................................ 35 Monozygotic twin pairs .................................................................................... 35 Hungarian coeliac disease patients ................................................................. 36 Coeliac disease patients from European Genetics Cluster ............................ 36 Samples in study I ....................................................................................... 36