Association of IRF5 polymorphisms with susceptibility to macrophage activation syndrome in patients with juvenile idiopathic arthritis.
OBJECTIVE
Systemic-onset juvenile idiopathic arthritis (systemic JIA) and macrophage activation syndrome (MAS), the most devastating complication of systemic JIA, are characterized by abnormal levels of proinflammatory cytokines. Interferon regulatory factor 5 (IRF5) is a member of the IRF family of transcription factors, and acts as a master transcription factor in the activation of genes encoding proinflammatory cytokines. Polymorphisms in the IRF5 gene have been associated with susceptibility to autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Our aim was to assess associations of IRF5 gene polymorphisms with susceptibility to systemic JIA and MAS.


METHODS
Three IRF5 single-nucleotide polymorphisms (rs729302, rs2004640, and rs2280714) were genotyped using TaqMan assays in 81 patients with systemic JIA (33 with MAS, 48 without) and 190 controls.


RESULTS
There were no associations of the IRF5 gene polymorphisms or haplotypes under study with susceptibility to systemic JIA. There was a significant association of the rs2004640 T allele with MAS susceptibility (OR 4.11; 95% CI 1.84, 9.16; p = 0.001). The IRF5 haplotype (rs729302 A, rs2004640 T, and rs2280714 T), which was reported as conferring an increased risk of SLE, was significantly associated with MAS susceptibility in patients with systemic JIA (OR 4.61; 95% CI 1.73, 12.3; p < 0.001).


CONCLUSIONS
IRF5 gene polymorphism is a genetic factor influencing susceptibility to MAS in patients with systemic JIA, and IRF5 contributes to the pathogenesis of MAS in these patients.
Department of Pediatrics, Yokohama City University Graduate School of Medicine; and the CNV Laboratory, DNA Chip Research Institute, Yokohama, Japan.
Masakatsu
M
Yanagimachi
Takuya
T
Naruto
Takako
T
Miyamae
Takuma
T
Hara
Masako
M
Kikuchi
Ryoki
R
Hara
Tomoyuki
T
Imagawa
Masaaki
M
Mori
Hidenori
H
Sato
Hiroaki
H
Goto
Shumpei
S
Yokota
D000293:Adolescent; D001171:Arthritis, Juvenile / Q000150:complications* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D055501:Macrophage Activation Syndrome / Q000209:etiology* / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors