The genetics of type I interferon in systemic lupus erythematosus.
The discovery that type I interferon (IFN)-inducible genes were strongly upregulated in peripheral blood in SLE over a decade ago sparked interest in understanding the relationship between type I IFN and SLE. Genome-wide association studies provide strong genetic evidence that type I IFNs are important for SLE risk. Of 47 genetic variants associated with SLE, over half (27/47, 57%) can be linked to type I IFN production or signaling. The recent identification of single gene mutations for disorders that share features with SLE--Aicardi-Goutières syndrome, chilblain lupus, and spondyloenchondrodysplasia--provide additional support for the hypothesis that type I IFNs are central drivers of SLE pathogenesis. These insights provide significant focus for efforts to tackle SLE therapeutically.
Department of Human Genetics, Genentech, Inc., South San Francisco, CA 94080, USA.
Paola G
PG
Bronson
Christina
C
Chaivorapol
Ward
W
Ortmann
Timothy W
TW
Behrens
Robert R
RR
Graham
D000818:Animals; D004195:Disease Models, Animal; D055106:Genome-Wide Association Study / Q000379:methods / Q000639:trends; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D009154:Mutation; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D007370:Interferon Type I