Leptin and leptin-related gene polymorphisms, obesity, and influenza A/H1N1 vaccine-induced immune responses in older individuals

Abstract

Obesity is a risk factor for complicated influenza A/H1N1 disease and poor vaccine immunogenicity. Leptin, an adipocyte-derived hormone/cytokine, has many immune regulatory functions and therefore could explain susceptibility to infections and poor vaccine outcomes. We recruited 159 healthy adults (5074 years old) who were immunized with inactivated TIV influenza vacci–ne that contained A/California/7/2009/H1N1 virus. We found a strong correlation between leptin concentration and BMI (r=0.55, p<0.0001), but no association with hemagglutination antibody inhibition (HAI), B-cell, or granzyme B responses. We found a slight correlation between leptin concentration and an immunosenescence marker (TREC: T-cell receptor excision circles) level (r=0.23, p=0.01). We found eight SNPs in the LEP/LEPR/GHRL genes that were associated with leptin levels and four SNPs in the PTPN1/LEPR/STAT3 genes associated with peripheral blood TREC levels (p<0.05). Heterozygosity of the synonymous variant rs2230604 in the PTPN1 gene was associated with a significantly lower (531 vs. 259, p = 0.005) TREC level, as compared to the homozygous major variant. We also found eight SNPs in the LEP/PPARG/CRP genes associated with variations in influenza-specific HAI and B-cell responses (p<0.05). Our results suggest that specific allelic variations in the leptin-related genes may influence adaptive immune responses to influenza vaccine.

Vitamin D, leptin and impact on immune response to seasonal influenza A/H1N1 vaccine in older persons

“…The SNP rs1175540 was associated with allele-dependent B-cell ELISPOT response at Day 28, and rs17793951 was associated with allele-dependent increase in HAI titer at Day 28 in this study cohort. 18 Based on the aforementioned interaction between VDR and PPAR genes, there could be an interaction influencing systemic vitamin D levels, but our results are not able to define a causal relationship.…”

“…The level of sensitivity for the leptin assay was 7.8 pg/ml, which has been previously reported. 18 The intra-class correlation coefficient (ICC) for this assay was 0.97.…”

“…18 A total of 159 subjects (50-74 years of age) were enrolled for a larger NIH-funded influenza vaccine study in Rochester, MN. All subjects were healthy, without any known immunocompromising conditions, and received one dose …”

“…18 Briefly, 96 tagSNPs from 12 candidate leptin signaling related genes were selected using source databases, such as International Hapmap Phase II, NIEHS SNPs, Seattle SNPs, and the 1000 Genomes Project. These genes included leptin (LEP), leptin receptor (LEPR), adiponectin (ADIPOQ), adiponectin receptor 1 (ADIPOPOR1), adiponectin receptor 2 (ADI-POR2), Janus kinase (JAK2), signal trasuducer and activator of transcription (STAT3), suppressor of cytokine signaling 3 (SOCS3), protein tyrosine phosphatase N1 (PTPN1), C-reactive protein (CRP), peroxisome-proliferator-activated receptor g (PPARG), and ghrelin/obestatin (GHRL) as has been previously described.…”

“…17 We have previously demonstrated our findings on the association of leptin and leptin-related gene polymorphisms on the immune response to influenza A/H1N1 vaccine in older persons. 18 In this study, we examined the effect of baseline serum 25-(OH) D status on both humoral and CMI responses following a single vaccination with the licensed seasonal trivalent 2010-2011 influenza vaccine (containing influenza A/California/ H1N1 like virus) in a healthy older cohort. Our primary aim was to correlate baseline 25-(OH) D levels with humoral and CMI response to influenza A/H1N1 vaccine.…”