Immunogenetics of Autoimmune Diseases

Description of Research

These diseases result from interaction between genetic and environmental factors. The single most important gene region regulating immune response is the (MHC) major histocompatibility complex, in humans the HLA gene complex. Polymorphisms within genes in this region are largely responsible for the genetic susceptibility to many autoimmune diseases including type 1 diabetes, celiac disease, ankylosing spondylitis, rheumatoid arthritis and multiple sclerosis.

We have performed genetic studies in the series of the Finnish Pediatric Diabetes Register and genetic screening for disease susceptibility for recruitment of subjects to several type 1 diabetes associated follow-up projects including DIPP, TRIGR, PRODIA, FINDIA, DIABIMMUNE and TEDDY where children at genetic risk have been followed-up in attempt to identify environmental risk factors and understand pathogenetic mechanisms responsible for destruction of pancreatic ß-cells.

Results based on definition of both HLA and non-HLA gene polymorphisms as well as clinical characteristics suggest heterogeneity in pathogenetic mechanisms of type 1 diabetes and different interactions between genetic and environmental factors in various phases of the autoimmune process leading to clinical disease. 
Many of the mentioned studies have included trials attempting to prevent clinical type 1 diabetes either before the appearance of diabetes associated autoimmunity (primary prevention) or after appearance of diabetes associated autoantibodies (secondary prevention).

Members of the Research Group

Johanna Lempainen, M.D., Ph.D., senior researcher
Antti-Pekka Laine, Ph.D., senior researcher,
Minna Kiviniemi, Ph.D., senior researcher
Mari-Liis Mikk, M.Sc. doctoral student
Zsofia Gombos, M.Sc. doctoral student
Mia Karlsson, technician
Terhi Laakso, technician
Piia Nurmi, technician
Anne Suominen, technician
Ritva Suominen, technician


Selected Publications

Ilonen J, Hammais A, Laine AP, Lempainen J, Vaarala O, Veijola R, Simell O, Knip M. Patterns of ß-cell autoantibody appearance and genetic associations during the first years of life. Diabetes 2013;62:3636-3640

Ziegler A-G, Rewers M, Simell O, Simell T, Lempainen J, Steck A, Winkler C, Ilonen J, Veijola R, Knip M, Bonifacio E, Eisenbarth GS. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 2013;309:2473-2479

Lempainen J, Laine AP, Hammais A, Toppari J, Simell O, Veijola R, Knip M, Ilonen J. Non-HLA gene effects on the disease process of type 1 diabetes: From HLA susceptibility to overt disease. J Autoimmun 2015;61:45-53

Ilonen J, Kiviniemi M, Lempainen J, Simell O, Toppari J, Veijola R. Knip M, the Finnish Pediatric Diabetess Register. Genetic susceptibility to type 1 diabetes in childhood – Estimation of HLA class II associated disease risk and class II effect in various phases of islet autoimmunity. Pediatr Diabetes 2016;17 Suppl 22:8-16

 Mikk M-L, Heikkinen T, El-Amir MI, Kiviniemi M, Laine A-P, Härkönen T, Veijola R, Toppari J, Knip M, Ilonen J, the Finnish Pediatric Diabetes Register. HLA-A*24:02, B*39:01 and B*39:06 allele association with type 1 diabetes is restricted to specific HLA-DR/DQ haplotypes in Finns. HLA;2017:89 (4):215-224



 Prof. Jorma Ilonen