Osteopontin Polymorphisms in Juvenile Idiopathic Arthritis and Pediatric Systemic Lupus Erythematosus

Abstract

Osteopontin (OPN), also named SPP1 or Eta-1, and originally identified as a bone matrix protein, has recently emerged as a proinflammatory cytokine. Posttranscriptional regulatory sequences are often found in 3' untranslated regions (UTR); therefore, we investigated the association between OPN levels and two SLE-associated 3' UTR polymorphisms in pediatric patients. Plasma OPN levels were tested by ELISA in 72 pediatric patients with systemic lupus erythematosus (pSLE; age<22 years), 16 oligoarticular juvenile idiopathic arthritis (oJIA) patients and 45 young, healthy controls. Increased plasma OPN was seen in pSLE (mean(plus or minus) SD = 14(plus or minus)4ng/ml) and oJIA (18(plus or minus)6ng/ml) compared with healthy controls (10(plus or minus)3 ng/ml) (P=0.002 and P<0.0001, respectively); oJIA had the highest levels among these samples (P=0.0002). In a multivariate regression analysis of the pSLE patients, both polymorphisms were independently associated with increased plasma OPN: the major allele of rs1126772 (P=0.004) and the minor allele of rs9138 (P=0.02). The OPN rs1126772 major allele was associated with arthritis in pSLE (P=0.02), but not nephritis. Furthermore, the rs1126772 major allele was associated with chronic damage in pSLE (P=0.008) but not disease activity, as assessed by validated instruments at the time of blood draw. In conclusion, the3' UTR polymorphism rs1126772was associated with increased plasma OPN, arthritis and chronic damage, but not nephritis, in pSLE. These data suggest that 3' UTR polymorphisms may regulate OPN levels and contribute to pediatric manifestations of arthritis.