Oil induced autoimmune arthritis

We here present evidence that a novel class of genes encoding regulatory leukocytereceptors may be of clinical importance in autoimmune diseases elicited by environmental exposure to immunoadjuvants, in particular mineral oils. The evidence is based on th e structural identification of the rat Oia2-gene, a quantitative trait locus conferring susceptibility to autoimmune arthritis elicited in susceptible rat strains by exposure to small doses of mineral oil. We show that the trait is linked to a novel gene complex encoding regulatory leukocyte receptors expressed by professional antigen presenting cell. The functional role of these receptors, their cellular expression patterns, and the fact that the syntenic chromosome interval in humans is linked to autoim mune disease constitute evidence that the model is valid for the study of human autoimmune disease. We further argue that oil induced arthritis represent a searchlight model of a multifactorial trait where genes and environmental factors interact in the p recipitation of disease. We present project plans for - molecular and functional studies of these receptors and their interaction with the environmental agent in the rat model (collaboration with Centre for Molecular Medicine (CMM), Karolinska Institutet , Stockholm) - cDNA sequencing and single nucleotide polymorphism (SNP) analyses of a register of individuals with rheumatoid arthritis (collaboration with the Rheumatological Department at Diakonhjemmet Hospital and CMM, Stockholm) - cDNA sequencing of selected individuals that have developed disease after exposure to hydraulic oils (collaboration with the National Institute of Occupational Health)