Publications

As the immune system develops, T cells are selected or regulated to become tolerant of self antigens and reactive against foreign antigens. In mice, the induction of such tolerance is thought to be attributable to the deletion of self-reactive cells. Here, we show that the human fetal immune system takes advantage of an additional mechanism: the generation of regulatory T cells (Tregs) that suppress fetal immune responses. We find that substantial numbers of maternal cells cross the placenta to reside in fetal lymph nodes, inducing the development of CD4+CD25highFoxP3+ Tregs that suppress fetal antimaternal immunity and persist at least until early adulthood. These findings reveal a form of antigen-specific tolerance in humans, induced in utero and probably active in regulating immune responses after birth.

BACKGROUND

Hypertension is a risk factor for coronary heart disease (CHD), but the causes of hypertension remain largely unknown. Genetic variation is thought to contribute to the etiology of hypertension. We tested a single-nucleotide polymorphism (SNP) (Lys67Arg, rs197922) in the Golgi SNAP Receptor Complex Member 2 (GOSR2) gene for association with hypertension and blood pressure (BP). We chose this SNP because it was nominally associated with CHD in earlier studies. Further, GOSR2 is located in a linkage region for hypertension and BP in human and animal studies.

METHODS

We used logistic and linear regression to test associations of the GOSR2 SNP with hypertension and BP among 3,528 blacks and 9,861 whites from the Atherosclerosis Risk in Communities (ARIC) study. Race-specific regression models of hypertension were adjusted for age and gender. Regression models of BP were further adjusted for antihypertensive medication use.

RESULTS

The GOSR2 Lys67 allele was associated with hypertension in whites (odds ratio (OR) = 1.09, P = 0.01) but not blacks (OR = 0.96, P = 0.47). The Lys67 allele was associated with increased systolic BP (SBP) in both races (0.87 mm Hg, P < 0.001 among whites and 1.05 mm Hg, P = 0.05 among blacks). A similar association in whites was observed for the GOSR2 SNP and SBP in the Women's Genome Health Study (WGHS) (OR = 1.03, P = 0.04). The OR remained unchanged after adjustment for antihypertensive medication use (OR = 1.03, P = 0.11), though it was no longer statistically significant.

CONCLUSIONS

We found evidence that a SNP in GOSR2 is modestly associated with hypertension in whites from the ARIC study and the WGHS.

BACKGROUND AND OBJECTIVES

Few studies have examined health literacy in patients with end stage kidney disease. We hypothesized that inadequate health literacy in a hemodialysis population is common and is associated with poorer access to kidney transplant wait-lists.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS

We enrolled 62 Black and White maintenance hemodialysis patients aged 18 to 75. We measured health literacy using the short form Test of Functional Health Literacy in Adults. Our primary outcomes were (1) time from dialysis start date to referral date for kidney transplant evaluation and (2) time from referral date to date placed on kidney transplant wait-list. We used Cox proportional hazard models to examine the association between health literacy (adequate versus inadequate) and our outcomes after controlling for demographics and co-morbid conditions.

RESULTS

Roughly one third (32.3%) of participants had inadequate health literacy. Forty-seven (75.8%) of participants were referred for transplant evaluation. Among those referred, 40 (85.1%) were wait-listed. Participants with inadequate health literacy had 78% lower hazard of referral for transplant evaluation than those with adequate health literacy (adjusted hazard ratio [AHR] 0.22; 95% confidence interval 0.08, 0.60; P = 0.003). The hazard ratio of being wait-listed by health literacy was not statistically different (AHR 0.80, 95% CI, 0.39, 1.61), P = 0.5).

CONCLUSIONS

Inadequate health literacy is common in our hemodialysis patient population and is associated with a lower hazard of referral for transplant evaluation. Strategies to reduce the impact of health literacy on the kidney transplant process should be explored.