Serologic Status of Routine Childhood Vaccines, Cytomegalovirus, and Epstein-Barr Virus in Children With Inflammatory Bowel Disease.

BACKGROUND: Data on the serologic status of childhood vaccines, cytomegalovirus (CMV) and Epstein-Barr virus (EBV), are limited in inflammatory bowel disease (IBD). Therefore, we evaluated vaccine coverage and seroprotection, along with CMV and EBV seropositivity, in pediatric IBD. METHODS: In a cross-sectional study, demographic data, IBD history, vaccine records, and serum for antibodies against measles, mumps, rubella, diphtheria, tetanus, varicella, hepatitis B (HBV), CMV, and EBV were collected from children with IBD. We evaluated potential factors associated with serologic status. RESULTS: Of 156 subjects, vaccine coverage was up to date for age in 93.5% for measles, mumps, rubella, 95.6% for diphtheria, tetanus, pertussis, polio, hemophilus influenza B, 75.8% for HBV, and 93.5% for varicella, including past infection and vaccination. Seroprotection was present in 65.8% for measles, 60.5% for mumps, 79.1% for rubella, 79.5% for diphtheria, 80.8% for tetanus, 70.5% for varicella, and 62.8% for HBV of subjects. Older age at diagnosis was associated with seroprotection among subjects with complete HBV (odds ratio [OR], 1.20; 95% confidence interval [CI], 1.03-1.39) and rubella series (OR, 1.18; 95% CI, 1.02-1.37). Older age at serum collection was associated with seroprotection among subjects with prior varicella vaccination or infection (OR, 1.69; 95% CI, 1.33-2.15). Only 25.2% and 37.8% demonstrated seropositivity to CMV and EBV, respectively. Among subjects on immunosuppressive medications, 75.3% and 62.4% were seronegative for CMV and EBV, respectively. CONCLUSIONS: Children with IBD have low serologic protection to childhood vaccines in spite of high vaccine coverage and universal vaccinations. Children with IBD, including a large proportion on immunosuppressive medications, have low seropositivity to CMV and EBV.

CRISPR-Cas9 genome editing in human cells occurs via the Fanconi anemia pathway.

CRISPR-Cas genome editing creates targeted DNA double-strand breaks (DSBs) that are processed by cellular repair pathways, including the incorporation of exogenous DNA via single-strand template repair (SSTR). To determine the genetic basis of SSTR in human cells, we developed a coupled inhibition-cutting system capable of interrogating multiple editing outcomes in the context of thousands of individual gene knockdowns. We found that human Cas9-induced SSTR requires the Fanconi anemia (FA) pathway, which is normally implicated in interstrand cross-link repair. The FA pathway does not directly impact error-prone, non-homologous end joining, but instead diverts repair toward SSTR. Furthermore, FANCD2 protein localizes to Cas9-induced DSBs, indicating a direct role in regulating genome editing. Since FA is itself a genetic disease, these data imply that patient genotype and/or transcriptome may impact the effectiveness of gene editing treatments and that treatments biased toward FA repair pathways could have therapeutic value.