Comparison of the three-dimensional chromatin structures of adolescent and adult peripheral blood B cells: implications for the study of pediatric autoimmune diseases.

Background/Purpose: Knowledge of the 3D genome is essential to elucidate genetic mechanisms driving autoimmune diseases. The 3D genome is distinct for each cell type, and it is uncertain whether cell lines faithfully recapitulate the 3D architecture of primary human cells or whether developmental aspects of the pediatric immune system require use of pediatric samples. We undertook a systematic analysis of B cells and B cell lines to compare 3D genomic features encompassing risk loci for juvenile idiopathic arthritis (JIA), systemic lupus (SLE), and type 1 diabetes (T1D). Methods: We isolated B cells from healthy individuals, ages 9-17. HiChIP was performed using CTCF antibody, and CTCF peaks were identified. CTCF loops within the pediatric were compared to three datasets: 1) self-called CTCF consensus peaks called within the pediatric samples, 2) ENCODE's publicly available GM12878 CTCF ChIP-seq peaks, and 3) ENCODE's primary B cell CTCF ChIPseq peaks from two adult females. Differential looping was assessed within the pediatric samples and each of the three peak datasets. Results: The number of consensus peaks called in the pediatric samples was similar to that identified in ENCODE's GM12878 and primary B cell datasets. We observed <1% of loops that demonstrated significantly differential looping between peaks called within the pediatric samples themselves and when called using ENCODE GM12878 peaks . Significant looping differences were even less when comparing loops of the pediatric called peaks to those of the ENCODE primary B cell peaks. When querying loops found in juvenile idiopathic arthritis, type 1 diabetes, or systemic lupus erythematosus risk haplotypes, we observed significant differences in only 2.2%, 1.0%, and 1.3% loops, respectively, when comparing peaks called within the pediatric samples and ENCODE GM12878 dataset. The differences were even less apparent when comparing loops called with the pediatric vs ENCODE adult primary B cell peak datasets.The 3D chromatin architecture in B cells is similar across pediatric, adult, and EBVtransformed cell lines. This conservation of 3D structure includes regions encompassing autoimmune risk haplotypes. Conclusion: Thus, even for pediatric autoimmune diseases, publicly available adult B cell and cell line datasets may be sufficient for assessing effects exerted in the 3D genomic space.

A pilot school-based health center intervention to improve asthma chronic care in high-poverty schools.

OBJECTIVE: To test the feasibility and effectiveness of a multifaceted intervention administered through school-based health centers (SBHCs) to improve asthma control for children in high-poverty schools with not well controlled asthma. METHODS: Students 4-14 years old with persistent asthma were enrolled from three SBHCs. The centers' advanced practice providers received training on evidence-based asthma guidelines. Students randomized to the intervention received directly observed therapy of their asthma controller medication, medication adjustments as needed by the centers' providers, and daily self-management support. Students randomized to usual care were referred back to their primary care provider (PCP) for routine asthma care. RESULTS: We enrolled 29 students. Students in the intervention group received their controller medication 92% of days they were in school. Ninety-four percent of follow-up assessments were completed. During the study, 11 of 12 intervention students had a step-up in medication; 2 of 15 usual care students were stepped up by their PCP. Asthma Control Test scores did not differ between groups, although there were significant improvements from baseline to the 7 month follow-up within each group (both p < .01). Both FEV1% predicted and FEV1/FVC ratio significantly worsened in the usual care group (both p = .001), but did not change in the intervention group (p = .76 and .28 respectively). CONCLUSIONS: Our pilot data suggest that a multifaceted intervention can be feasibly administered through SBHCs in communities with health disparities. Despite the small sample size, spirometry detected advantages in the intervention group. Further study is needed to optimize the intervention and evaluate outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03032744.

Immunogenicity of trivalent influenza vaccine in extremely low-birth-weight, premature versus term infants.

BACKGROUND: Influenza vaccine immunogenicity in premature infants is incompletely characterized. OBJECTIVE: To assess the immunogenicity of trivalent, inactivated influenza vaccine (TIV) in extremely low-birth-weight (≤ 1000 g birth weight) premature (<30 weeks gestation) infants. We hypothesized that geometric mean titers of influenza antibody would be lower in premature than in full-term (FT) (≥ 37 week) infants. DESIGN/METHODS: In this prospective multicenter study, former premature and FT infants who were 6 to 17 months of age received 2 doses of TIV during the 2006-2007 or 2007-2008 influenza seasons. Sera were drawn before dose 1, and 4 to 6 weeks after dose 2. Antibody was measured by hemagglutination inhibition. RESULTS: Over 2 years, 41 premature and 42 FT infants were enrolled; 36 and 33 of these infants, respectively, had postvaccination titers available. Premature infants weighed less (mean, 1.3-1.8 kg difference) at the time of immunization than FT infants. Prevaccination titers did not differ between groups. Premature infants had higher postvaccination antibody geometric mean titers than FT infants to H1 (2006-2007, 1:513 vs. 1:91, P = 0.03; 2007-2008, 1:363 vs. 1:189, P = 0.02) and B/Victoria (2006-2007, 1:51 vs. 1:10, P = 0.02). More premature than FT infants had antibody titers ≥ 1:32 to B/Victoria (85% vs. 60%, P = 0.04) in 2007-2008. Two (5%) premature and 8 (19%) FT infants had adverse events, primarily fever, within 72 hours after vaccination. No child had medically diagnosed influenza. CONCLUSIONS: Former premature infants had antibody responses to 2 TIV doses higher than or equal to those of FT children. Two TIV doses are immunogenic and well tolerated in extremely low-birth-weight, premature infants 6 to 17 months old.