Effects of psychological stress and cytokine genes on humoral immune response to tetanus toxoid adsorbed in family caregivers of Alzheimer's disease patients

Vaccine-induced antibody response is a complex process determined by both genetic and non-genetic factors. A family-based cohort study was conducted to assess the effects of chronic psychological stress and cytokines genes on the antibody response to tetanus vaccine and to estimate the heritability of antibody response in 119 spouses and offspring of community-dwelling patients with Alzheimer's disease (AD). Psychological stress was measured by the Perceived Stress Scale (PSS) and the Center for Epidemiologic Research-Depression (CES-D) scale. Blood samples were collected at baseline and one month after tetanus vaccination. Ten single nucleotide polymorphism (SNP) markers on IL-1beta, IL-2, IL-12, TNF-alpha, IL-10, and IL-4 were genotyped. The anti-tetanus (TT) IgG was tested using ELISA. The antibody response was analyzed as the difference between the log10 (post-anti-TT IgG) and log10 (pre-anti-TT IgG). The psychological stress variables were analyzed using their original scales and factor scores obtained by principal component analyses. The results using mixed models showed that every point increase in the CES-D score was associated with 10.75% less antibody fold increase (p=0.0023), every point increase in the PSS score was associated with 4.8% less antibody fold increase (p=0.075), the effect of the factor score formed by factor loadings from CES-D and PSS scores was even larger, with every point increase associated with 31% less antibody fold increase (p=0.019). The TNF-alpha -238 A>G GG genotype was associated with 215.0% greater antibody fold increase compared to the AA+AG genotypes (p=0.0028). Age and self-reported arthritis were also positively associated with the antibody response. The crude and adjusted heritability estimates in the parent-offspring pairs for the post-anti-TT IgG were 0.40 (95% CI: -0.05, 0.86) and 0.28 (95% CI: -0.18, 0.76), respectively. The study provided additional evidence on the detrimental effects of psychological stress on the antibody response to the tetanus vaccine. Furthermore, the results suggested that the TNF-alpha -238 A/G locus may influence the antibody response through its regulation on transcription and production of TNF-alpha.