Genetics of autoimmune neuroinflammation.
Detection of gene variants affecting the risk for multiple sclerosis provides insights into mechanisms central for autoaggressive neuroinflammation. Major histocompatibility complex (MHC) class II genes, and probably also MHC class I genes, regulate both human multiple sclerosis and rodent experimental autoimmune encephalomyelitis. However, the functional understanding of the MHC regulation requires further experimentation. Genome scans in human multiple sclerosis have failed to demonstrate significant non-MHC loci with genome-wide significance, but approximately 50 such loci have been described in different rodent experimental autoimmune encephalomyelitis models. Positional cloning of individual rodent genes is difficult, but genes or small genome regions now emerge. Association studies in large human cohorts are needed to confirm the human relevance of rodent genes and such cohorts will also be used for single nucleotide polymorphism-based whole-genome screening. It is realistic to assume that several non-MHC genes regulating autoimmune neuroinflammation, including target tissue responses, will be pinpointed in the next ten years. At the moment there are a few hot candidates, including MHC2TA, PRKCA and IL7R.
Olsson
Tomas
T
Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine (L8:04), Karolinska University Hospital, 171 76 Stockholm, Sweden. tomas.olsson@cmm.ki.se
Jagodic
Maja
M
Piehl
Fredrik
F
Wallström
Erik
E
D000818:Animals; D015551:Autoimmunity / Q000235:genetics*; D002874:Chromosome Mapping; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D008285:Major Histocompatibility Complex / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics*