title: Schizophrenia, rheumatoid arthritis and natural resistance genes.
abstract: The strong negative correlation between schizophrenia and rheumatoid arthritis might provide clues as to the aetiology of these two diseases. An immunological explanation has been sought in the HLA sector of the major histocompatibility complex, which has been shown to have a role in the development of rheumatoid arthritis. The search for an association between schizophrenia and HLA haplotypes, however, has yielded only controversial results. Nevertheless, an autoimmune aetiology is still suspected. The recent demonstration of geographical co-occurrence of high rates of schizophrenia and flavivirus infection suggests, for the first time, that a natural resistance gene (NRG) might be involved in the aetiology of schizophrenia. Such a NRG is carried by the C3H/RV mouse, providing protection against lethal infection by flavivirus, but not by the histocompatible C3H/He mouse. Furthermore, the C3H/He mouse has proved to be a good model for the development of Lyme arthritis, resulting from infection by Borrelia burgdorferi. It is suggested that there is a possibility that the C3H/RV mouse, which is known to be resistant to both flavivirus and rickettsia, may also be resistant to borrelia, since the Ixodid tick vector of flavivirus is the vector for all three of these organisms. If so, then the C3H/RV mouse would resist infection by borrelia, and could not develop Lyme arthritis. It is hypothesised, therefore, that despite the histocompatibility of these two strains, while the C3H/He mouse is vulnerable to Lyme arthritis, the C3H/RV mouse may be resistant. As a consequence, NRGs may play a part in triggering autoimmune disease, with HLA antigens responsible for its further development. This would indicate that the negative association of schizophrenia and rheumatoid arthritis could result from resistance or vulnerability to certain infections.
authors.affiliation: Department of Psychiatry, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Rubinstein
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D018177:Flavivirus Infections / Q000235:genetics / Q000276:immunology; D005802:Genes, MHC Class II / Q000235:genetics* / Q000276:immunology; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics* / Q000276:immunology; D008193:Lyme Disease / Q000235:genetics / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D012559:Schizophrenia / Q000235:genetics* / Q000276:immunology
chemical_list: D006680:HLA Antigens