Differential HLA gene expression in measles vaccine seropositive and seronegative subjects: a pilot study.

Abstract

This is the first study using GeneChip technology to elucidate genetic determinants of the measles vaccine response. A comparative gene expression study was conducted using Affymetrix's Human GeneChip U-95A in 5 human subjects immunized with a 'booster' dose of measles vaccine (Attenuax, Merck) to determine whether serologically distinct subjects exhibit differential expression of human leukocyte antigen (HLA) genes. Healthy individuals aged 15-25 y, previously immunized with 2 doses of measles-mumps-rubella-II (MMR-II) vaccine, were classified as measles vaccine immunoglobulin G-specific antibody seronegatives (n = 2) and seropositives (n = 3). Changes in expression of HLA genes in seronegatives and seropositives were studied on days 7 and 14 post-measles vaccination using Microarray Suite 5.0 (MAS 5.0). There was increased expression of the HLA class I-B (p = 0.0002), HLA class II cluster of DMA, DMB, TAP1, TAP2 (p = 0.0007) and HLA-DR (p = 0.0001) genes, and decreased expression of HLA class I MICB molecule (p = 1), HLA class I-A (p = 0.9999) and major histocompatibility complex class III HSP 70 (p = 0.9999) genes on day 7 or day 14 postvaccination in seropositives compared with seronegatives. These results suggest an association between antibody response and differential HLA gene activation and may explain one potential mechanism underlying measles vaccine non-response.