Oil induced autoimmune disease

We here present evidence that environmental exposure to immunoadjuvants in particular mineral oils, may precipitate autoimmune diseases in susceptible individuals, and that a novel class of genes encoding leukocyte regulatory receptors contribute to this susceptibility. The evidence is based on the structural identification of the rat Oia2-gene, a quantitative trait locus conferring susceptibility to autoimmune arthritis elicited in susceptible rat strains by skin exposure to small doses of mineral oil. W e show that the trait is linked to a novel gene complex that we have called APLEC, encoding regulatory leukocyte receptors expressed by professional antigen presenting cells. The functional role of these receptors, their cellular expression patterns, and the finding of genetic association between a gene in homologous human gene complex and rheumatoid arthritis (RA) constitute evidence that the model is valid for the study of human autoimmune diseases. We argue that oil induced arthritis represent a search light model of a multifactorial trait where genes and environmental factors interact in the precipitation of disease. We present project plans for - Molecular and functional studies of these receptors and their interaction with the environmental agent i n the rat model (collaboration with Centre for Molecular Medicine (CMM), Karolinska Institutet, Stockholm) - As a model system for epistatic interactions similar studies of the functionally related CD300 receptors and their interaction with the environm ental agent in the human as well as in the rat model - cDNA sequencing and single nucleotide polymorphism (SNP) analyses of a register of individuals with rheumatoid arthritis (collaboration with the Rheumatological Department at Diakonhjemmet Hospital an d CMM, Stockholm) - SNP analyses of individuals that have developed disease after exposure to hydraulic oils (collaboration with the National Institute of Occupational Health)