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.

Introduction Environmental factors play a pathogenic role in the aetiology of Kawasaki Disease (KD). Fine particulate matter (aerodynamic diameter less than or equal to a 2.5-mm cut point, PM2.5) is a measurable component of ambient urban pollution. Environmental influences associated with weather, spatial location, and temporal season have been shown to contribute, however the short term environmental triggers which contribute to the clinically recognised onset event of KD remain unclear. Potentially, short-term pollution exposures act as covariates to clinical disease presentation and outcome, including measures of coronary artery involvement. Methods A case-crossover study design was used to analyse associations of short-term PM2.5 exposures with the event date of KD symptom onset (fever) from cases residing in the metropolitan regions of Boston, Toronto, Cleveland, Chicago, San Diego, Denver, and Salt Lake City. Time trends, seasonality, month, and weekday were controlled for by matching. Selected exposure windows (up to 14 days) of PM2.5. were examined. Results We have assembled PM2.5 exposure measurements from urban monitors and have carefully imputed PM2.5 to provide day-to-day temporal variability and resolution for reliable time series indexes of pollution exposures for each metropolitan area. 3,009 KD events were included where the subject resided within one of the study metro areas and the onset of disease occurred during the years with available PM2.5 monitoring. The estimated relative risks (and 95% CI’s) of an onset event of KD associated with a 10 µg/m3 PM2.5 lagged moving average concentration of lagged exposure period (concurrent day and preceding day (s)) revealed no evidence of a consistent, statistically significant, positive association between elevated exposure to PM2.5 and elevated risk of KD onset. Extended analysis with stratification by city, sex, and age did not provide evidence of a consistent, statistically significant, positive association between elevated exposure to PM2.5 and elevated risk of KD onset for any of the strata. Conclusions Well-constructed, environmental epidemiology studies examining the triggers of disease onset and exacerbation in paediatric rheumatic diseases are few and far between. While our results failed to establish a risk of the event of KD fever onset with short-term ambient particulate pollution exposure, negative findings from this study add to the growing field of particulate induced environmental epidemiology research of Kawasaki Disease.