OBJECTIVES To characterize the epidemiology and clinical course of children with juvenile idiopathic arthritis-associated uveitis (JIA-U) in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry and explore differences between African American (AA) and Non-Hispanic White (NHW) children. METHODS There were 3,967 NHW and AA children with JIA enrolled in the CARRA Registry. Demographic and disease-related data were collected from time of diagnosis to enrollment. Children with JIA alone were compared to those with JIA-U. Children with JIA-U were then compared by race. RESULTS Mean age of children with JIA-U was 11.4 years (±4.5), 76.9% were female and 2.8% were AA. Children with JIA-U were younger at arthritis onset, female, required more medications, had <5 joints involved, had oligoarticular JIA, and ANA (+), RF (−) and anti-CCP (−). AA children with JIA-U had decreased uveitis frequency, were older at arthritis onset and more frequently diagnosed with enthesitis-related JIA. Predictors of uveitis development include female gender, early age of arthritis onset, and oligoarticular persistent and extended JIA classification, whereas polyarticular RF-positive JIA was protective. CONCLUSIONS The prevalence of JIA-U in AA and NHW children is 11.6% in the CARRA registry. Known risk markers (ANA, age at arthritis onset, and oligoarticular JIA) were more frequent in our JIA-U cohort. AA children had a lower frequency of JIA-U. There were significant differences in age of arthritis onset and JIA subtype between NHW and AA children, although the ANA, RF and HLA-B27 were similar. Exploration of race as a risk factor should be considered.

BackgroundThe genetic and immunological factors that contribute to differences in susceptibility and progression between sub-types of inflammatory and autoimmune diseases continue to be elucidated. Inflammatory bowel disease and juvenile idiopathic arthritis are both clinically heterogeneous and known to be due in part to abnormal regulation of gene activity in diverse immune cell types. Comparative genomic analysis of these conditions is expected to reveal differences in underlying genetic mechanisms of disease.MethodsWe performed RNA-Seq on whole blood samples from 202 patients with oligoarticular, polyarticular, or systemic juvenile idiopathic arthritis, or with Crohn’s disease or ulcerative colitis, as well as healthy controls, to characterize differences in gene expression. Gene ontology analysis combined with Blood Transcript Module and Blood Informative Transcript analysis was used to infer immunological differences. Comparative expression quantitative trait locus (eQTL) analysis was used to quantify disease-specific regulation of transcript abundance.ResultsA pattern of differentially expressed genes and pathways reveals a gradient of disease spanning from healthy controls to oligoarticular, polyarticular, and systemic juvenile idiopathic arthritis (JIA); Crohn’s disease; and ulcerative colitis. Transcriptional risk scores also provide good discrimination of controls, JIA, and IBD. Most eQTL are found to have similar effects across disease sub-types, but we also identify disease-specific eQTL at loci associated with disease by GWAS.ConclusionJIA and IBD are characterized by divergent peripheral blood transcriptomes, the genetic regulation of which displays limited disease specificity, implying that disease-specific genetic influences are largely independent of, or downstream of, eQTL effects.Electronic supplementary materialThe online version of this article (10.1186/s13073-018-0558-x) contains supplementary material, which is available to authorized users.

Objective To determine the validity and reliability of a novel questionnaire to measure vision related quality of life (VRQOL) in children 8–18 years old for use in juvenile idiopathic arthritis-associated uveitis (JIA-U) –Effects of Youngsters’ Eyesight on Quality of Life (EYE-Q). Methods Several steps validated the EYE-Q. We interviewed experts and children on how vision affects a child’s activities. We developed new items and selected relevant items from existing instruments. We administered initial versions of the EYE-Q to normal-sighted children and those with JIA-U. For this study, children with various (or no) ocular conditions were recruited from a clinical population. Visual acuity (VA) and contrast sensitivity were performed, and the EYE-Q and Pediatric Quality of Life Inventory (PedsQL) were administered. The EYE-Q was repeated 10 days later. Patients, parents and physicians rated vision severity. Results Of 120 patients, 48% were female, 46.7% had no visual impairment (VI), and 52% had bilateral eye involvement. Mean age was 11.3 years. There were significant differences in the measures based on VA (p<0.001). Children with more severe VA and bilateral eye involvement had worse EYE-Q scores (p<0.001). There were significant associations between the EYE-Q and PedsQL (r = 0.375), repeat EYE-Q (r = 0.864), and clinical measures of ocular disease (r = −0.620). Conclusions Our study provides evidence of the validity and reliability of the EYE-Q in the measurement of VRQOL. The EYE-Q may complement clinical measures of VI and overall QOL and become an important tool in the assessment of QOL in JIA-U.

Objective Associations between shared epitope (SE)-encoding HLA-DRB1 alleles and rheumatoid arthritis (RA) are well established but only a limited number of studies have investigated these alleles in childhood onset RA (CORA), defined as rheumatoid factor (RF) and/or anti-citrullinated protein antibody (ACPA) positive juvenile idiopathic arthritis. We sought to investigate the largest cohort of CORA for association with SE alleles, and to determine whether there was a hierarchy of risk based on the amino acid sequence of the SE. Methods High resolution HLA-DRB1 genotypes were obtained for 204 children with CORA and 373 healthy controls. Odds ratios (OR) and 95% CI were calculated for different SE-encoding HLA-DRB1 alleles. We also calculated genotypic OR for combinations of SE alleles classified into S2, S3P or L alleles, based on amino acids in positions 70-74 of the DRβ1 chain as proposed by Tezenas Du Montcel et al (2005). Results We confirmed associations between HLA-DRB1 SE alleles and CORA (76% of cases versus 46% of controls; OR=3.81 (95%CI 2.4-6.0), p <1×10−7). We also found associations between individual SE alleles (HLA-DRB1*0101, *0401, *0404, *0405, *0408 and *1001) and CORA. Genotype-specific risk estimates suggested a hierarchy of risk, with the highest risk among those heterozygous for S2/S3P (OR=22.3 (9.9-50.5) p <0.0001). Conclusions We confirm the association between SE-encoding HLA-DRB1 alleles and susceptibility to CORA. The excess risk conferred by individuals who carry the combination of S2/S3P risk alleles suggests that children with DRβ1 chains containing KRAA and Q/RRRAA are especially prone to RA.