Genetic variation, Fcγ receptors, KIRs and infection: the evolution of autoimmunity.
Recent work has emphasised the marked genetic variability that exists in the Fc receptor locus. This variation can contribute to the risk of autoimmune disease in both mice and humans, but can also have a profound impact on defence against infection. Using FcγRIIB and FcγRIIIB as examples, we demonstrate that variations associated with increased susceptibility to autoimmunity may be maintained in populations for their beneficial effect against infection. We examine the KIR locus from the same perspective and highlight similarities between the two loci. Intense selection pressure by pathogens presumably accounts for the marked variability within both regions and leads to susceptibility to autoimmunity for some alleles.
Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Box 139 Addenbrooke's Hospital, Hills Road, Cambridge CB2 0XY, UK.
Marion
M
Espeli
Heather A
HA
Niederer
James A
JA
Traherne
John
J
Trowsdale
Kenneth Gc
KG
Smith
D015551:Autoimmunity / Q000235:genetics* / Q000276:immunology*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D007239:Infections / Q000235:genetics / Q000276:immunology*; D017452:Receptors, IgG / Q000235:genetics* / Q000276:immunology; D054340:Receptors, KIR / Q000235:genetics* / Q000276:immunology
D017452:Receptors, IgG; D054340:Receptors, KIR