Variability in Laboratory Immune Parameters Is Associated with Stress Hormone Receptor Polymorphisms

Abstract

Objectives: Interpretation of laboratory immune data in healthy human subjects is often challenging due to wide inter-subject variability. Since endocrine and immune mediators have been mutually interlinked, a potential explanation for the significant variability seen in immune data even when controlled for technical variability and demographics is differences in the binding affinity of ligand with hormone receptors on the surface of immune cells, which can be associated with single nucleotide polymorphisms (SNP). Methods: We categorized immunoregulatory cellular profiles from PBMC of 207 healthy volunteers according to glucocorticoid receptor (GR: Bcl1, TthIIII, and A3669G) and β₂-adrenergic receptor (β2AR: Gly16Arg and Gln27Glu) polymorphisms. Subjects were genotyped for each SNP, and Th1, Th2, Th1/Th2 ratio, regulatory T cell (T_reg), Tr1, and Th3 cell numbers were assessed. Immune parameters in the SNP groups were compared to the wild type (WT). Results: Significant differences were observed in Th2 and the Th1/Th2 ratio for the β2AR SNP Gly16Arg. Th1, the Th1/Th2 ratio, and Tr1 differed significantly by SNP of Gln27Glu. In addition, the effect of age on Th2 and the effect of the body mass index on the Th1/Th2 ratio significantly differed across subtypes of the Gly16Arg SNP. Significant differences based on allergic status and gender were also seen for T_reg, Th1, and Th2 across Gly16Arg, Gln27Glu, and TthIIII SNP. Conclusions: These data suggest that SNP from various components of the stress-immune network may be useful for subgrouping of immune responses to more accurately categorize psychoneuroimmunological components of stress risk in individual subjects. This approach may have significant research and clinical potential.

The Impact of Self-Reported Psychological Stress Levels on Changes to Peripheral Blood Immune Biomarkers in Recreational Marathon Runners during Training and Recovery

“…PBMC were isolated using a Ficoll-Hypaque gradient as previously described [32]. Briefly, cells were centrifuged at 650 g for 30 min, washed twice in HBSS, and then resuspended in 1 ml HBSS.…”

“…T cell populations in PBMC were analyzed by flow cytometry according to previously described methods [32]. Briefly, 1 × 10 6 PBMC were incubated with the manufacturer's recommended amount of the following surface antibodies: CD3-ECD, CD4-ECD (all from Beckman Coulter, Miami, Fla., USA), and/or CD25-PECy7 (eBioscience, San Diego, Calif., USA).…”

Cytokine balance and behavioral intervention; findings from the Peer Approaches to Lupus Self-Management (PALS) project

“…However, members of our study team have published work that addresses this in the context of various SNPs as biomarkers and Th1/Th2 cytokine balance data, and there are many published case control-type studies that show various baseline data but this is highly variable because of study population differences and technical differences in anti-body sources, instruments and even times of the day [75]. …”

“…Given the significance of stress effects on immune function, analysis of blood immune-phenotype and T cell activation for intracellular cytokine detection was achieved by flow cytometry, within the singlet cell gate, after labeling with commercial monoclonal antibodies using methodology previously described [71]. Immune profiles associated with disease activity were determined by Th1/Th2 cytokine balance in peripheral blood mononuclear cells (PBMC).…”

Effects of Short Term <i>in vitro</i> Stress Hormone Exposure on Regulatory T Cell Number and Function in Asthma

“…Venous blood was collected into heparinized tubes and PBMC were isolated using a ficoll-hypaque gradient as previously described (Rehm et al, 2012). Briefly, cells were centrifuged at 650 g for 30 min, washed twice in HBSS and then resuspended in 1 mL cRPMI supplemented with 5% FBS.…”