Publications

The autoimmune regulator (Aire) is essential for prevention of autoimmunity; its role is best understood in the thymus, where it promotes self-tolerance through tissue-specific antigen (TSA) expression. Recently, extrathymic Aire-expressing cells (eTACs) have been described in murine secondary lymphoid organs, but the identity of such cells and their role in immune tolerance remains unclear. Here we have shown that eTACs are a discrete major histocompatibility complex class II (MHC II)(hi), CD80(lo), CD86(lo), epithelial cell adhesion molecule (EpCAM)(hi), CD45(lo) bone marrow-derived peripheral antigen-presenting cell (APC) population. We also have demonstrated that eTACs can functionally inactivate CD4⁺ T cells through a mechanism that does not require regulatory T cells (Treg) and is resistant to innate inflammatory stimuli. Together, these findings further define eTACs as a distinct tolerogenic cell population in secondary lymphoid organs.

BACKGROUND

Airway hyperresponsiveness (AHR), a primary characteristic of asthma, involves increased airway smooth muscle contractility in response to certain exposures. We sought to determine whether common genetic variants were associated with AHR severity.

METHODS

A genome-wide association study (GWAS) of AHR, quantified as the natural log of the dosage of methacholine causing a 20% drop in FEV1, was performed with 994 non-Hispanic white asthmatic subjects from three drug clinical trials: CAMP, CARE, and ACRN. Genotyping was performed on Affymetrix 6.0 arrays, and imputed data based on HapMap Phase 2, was used to measure the association of SNPs with AHR using a linear regression model. Replication of primary findings was attempted in 650 white subjects from DAG, and 3,354 white subjects from LHS. Evidence that the top SNPs were eQTL of their respective genes was sought using expression data available for 419 white CAMP subjects.

RESULTS

The top primary GWAS associations were in rs848788 (P-value 7.2E-07) and rs6731443 (P-value 2.5E-06), located within the ITGB5 and AGFG1 genes, respectively. The AGFG1 result replicated at a nominally significant level in one independent population (LHS P-value 0.012), and the SNP had a nominally significant unadjusted P-value (0.0067) for being an eQTL of AGFG1.

CONCLUSIONS

Based on current knowledge of ITGB5 and AGFG1, our results suggest that variants within these genes may be involved in modulating AHR. Future functional studies are required to confirm that our associations represent true biologically significant findings.

PURPOSE

To examine the association between race/ethnicity and human papillomavirus (HPV) vaccine initiation and to determine how access to health care influences this relationship.

METHODS

We used nationally representative data from the National Survey of Family Growth to assess HPV vaccine initiation in 2,168 females aged 15-24 years. A series of regression analyses were performed to determine the independent effect of race/ethnicity on HPV vaccine initiation after controlling for sociodemographic variables and health care access measures. Age-stratified regression analyses were also performed to assess whether the relationship between race/ethnicity and HPV vaccine initiation differed among females aged 15-18 and 19-24 years.

RESULTS

There were significant racial/ethnic disparities in HPV vaccination; United States (US)-born Hispanics, foreign-born Hispanics, and African-Americans were less likely to have initiated vaccination than were whites (p < .001). Adjusting for sociodemographic characteristics attenuated the disparity for both US-born and foreign-born Hispanics (adjusted odds ratio [AOR], .76; 95% confidence interval [CI], .50-1.16; and AOR, .67; 95% CI, .37-1.19) but not for African-Americans (AOR, .47, 95% CI, .33-.66). Adding health care access measures further attenuated the disparity for US-born and foreign-born Hispanics (AOR, .85, 95% CI, .54-1.34; and AOR, .84, 95% CI, .45-1.55). However, African-Americans remained less likely than whites to have initiated vaccination (AOR, .49, 95% CI, .36-.68). These racial/ethnic trends were similar for females aged 15-18 and 19-24 years.

CONCLUSIONS

Lower rates of HPV vaccination among African-American females do not appear to be explained by differential access to health care. More research is necessary to elucidate factors contributing to HPV vaccination in this population.