In our study, IL1RN was the only candidate locus associated with systemic JIA. The implicated SNPs are among the strongest known determinants of IL1RN and interleukin-1 receptor antagonist levels, linking low expression with increased systemic JIA risk. Homozygous high expression alleles predicted nonresponsiveness to anakinra therapy, making them ideal candidate biomarkers to guide systemic JIA treatment. This study is an important first step toward the personalized treatment of systemic JIA.

Children with systemic lupus erythematosus (SLE) have a high prevalence of antiphospholipid (aPL) antibodies and are at increased risk for aPL-related thrombosis. We investigated the association between annexin A5 anticoagulant activity and antibodies to the domain I portion of β2-glycoprotein I (anti-DI antibodies), and propose a potential mechanism for the pathogenesis of aPL-related thrombosis. Using samples from 183 children with SLE collected during the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial, we examined resistance to the anticoagulant effects of annexin A5, using the annexin A5 resistance (A5R) assay, and evaluated for anti-DI IgG antibodies. Children with SLE had higher frequency of anti-D1 antibodies (p=0.014) and significantly reduced A5R compared to pediatric controls: mean A5R = 172 ± 30 % versus 242 ± 32 % (p<0.0001). Children with SLE and positive anti-DI antibodies had significantly lower mean A5R levels compared to those with negative anti-DI antibodies: mean A5R = 155 ± 24 % versus 177 ± 30% (p<0.0001). In multivariate analysis, anti-DI antibodies (p=0.013) and lupus anticoagulant (LA) (p=0.036) were both independently associated with reduced A5R. Children with SLE have significantly reduced annexin A5 anticoagulant activity that is associated with the presence of LA and anti-DI antibodies.

Lupus nephritis (LN) affects many patients with juvenile systemic lupus erythematosus (SLE) and is a significant cause of disease morbidity. Membraneous plus proliferative LN (M+PLN) may represent a more difficult to treat subtype of juvenile LN, compared to isolated proliferative LN (PLN.) In this retrospective observational study, we utilized data from the Childhood Arthritis and Rheumatism Research Alliance (CARRA) registry to compare response rates for pediatric M+PLN versus PLN. Response was assessed at the most recent CARRA registry visit gathered ≥ 6 months after diagnostic kidney biopsy. Estimated glomerular filtration rate (GFR) less than 90 ml/min/1.73m2, indicating renal insufficiency, was found in 16.1% of patients with M+PLN and 6.1% of patients with PLN (P=0.071). We found no significant difference in achievement of response in either hematuria or proteinuria between PLN and M+PLN groups or between subgroups determined by presence of class III vs. class IV proliferative disease. Exposure rates to mycophenolate, cyclophosphamide, and rituximab were similar between groups. Future studies will be necessary to correlate pediatric LN renal histology data with treatment response as well as other disease outcome measures.