Publications

OBJECTIVE

Epigenetic modifications have previously been associated with rheumatoid arthritis (RA). In this study, we aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with any of 4 clinical outcomes among RA patients.

METHODS

Peripheral blood samples were obtained from 63 patients in the University of California, San Francisco RA cohort (all satisfied the American College of Rheumatology classification criteria; 57 were seropositive for rheumatoid factor and/or anti-cyclic citrullinated protein). Fluorescence-activated cell sorting was used to separate the cells into 4 immune cell subpopulations (CD14+ monocytes, CD19+ B cells, CD4+ naive T cells, and CD4+ memory T cells) per individual, and 229 epigenome-wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips. Differentially methylated positions and regions associated with the Clinical Disease Activity Index score, erosive disease, RA Articular Damage score, Sharp score, medication at time of blood draw, smoking status, and disease duration were identified using robust regression models and empirical Bayes variance estimators.

RESULTS

Differential methylation of CpG sites associated with clinical outcomes was observed in all 4 cell types. Hypomethylated regions in the CYP2E1 and DUSP22 gene promoters were associated with active and erosive disease, respectively. Pathway analyses suggested that the biologic mechanisms underlying each clinical outcome are cell type-specific. Evidence of independent effects on DNA methylation from smoking, medication use, and disease duration were also identified.

CONCLUSION

Methylation signatures specific to RA clinical outcomes may have utility as biomarkers or predictors of exposure, disease progression, and disease severity.

We estimated mortality rate and predictors of death in children and adolescents who acquired HIV through mother-to-child transmission in Paraguay. In 2000-2014, we conducted a cohort study among children and adolescents aged < 15 years. We abstracted data from medical records and death certificates. We used the Cox proportional hazards model for the multivariable analysis of mortality predictors. A total of 302 subjects were included in the survey; 216 (71.5%) were younger than 5 years, 148 (51.0%) were male, and 214 (70.9%) resided in the Asunción metropolitan area. There were 52 (17.2%) deaths, resulting in an overall mortality rate of 2.06 deaths per 100 person-years. The children and adolescents with hemoglobin levels ≤ 9 g/dL at baseline had a 2-times higher hazard of death compared with those who had levels > 9 g/dL (HR 2.27, 95% CI 1.01-5.10). The mortality of HIV-infected children and adolescents in Paraguay is high, and anemia is associated with mortality. Improving prenatal screening to find cases earlier and improving pediatric follow-up are needed.