Blood hormones and torque teno virus in peripheral blood mononuclear cells

Abstract

Men and women respond differently to infectious diseases. Women show less morbidity and mortality, partially due to the differences in sex hormone levels which can influence the immune response. Torque teno virus (TTV) is non-pathogenic and ubiquitously present in serum from a large proportion (up to 90%) of adult humans with virus levels correlating with the status of the host immune response. The source of TTV replication is unknown, but T-lymphocytes have been proposed. In this study we investigated the presence and levels of TTV in peripheral blood mononuclear cells (PBMCs) in premenopausal (pre-MP) women, post-menopausal (post-MP) women, and men, and determined their serum sex hormone levels. Of the examined subjects (n = 27), we found presence of TTV in PMBC from 17.6% pre-MP (n = 17), 25.0% post-MP (n = 4) and 50.0% men (n = 6). The levels of TTV/μg DNA were lower among TTV-positive men and post-MP women compared to pre-MP women. All the positive pre-MP women were either anovulatory, hypothyroid, or both. In addition, the TTV-positive pre-MP women had significantly lower progesterone levels compared to TTV-negative pre-MP women. Although our study was performed on a limited number of subjects, the data suggests that TTV in PBMC is associated with an anovulatory menstrual cycle with low progesterone levels, and possibly with male sex.

Keywords: Aging; Anovulatory; Commensal viruses; Estrogen; Hematology; Hypothyroidism; Immune response; Immunity; Immunodeficiency; Immunology; Infection; Infectious disease; Menstrual cycle; Microbiome; Reproductive hormone; Sex difference; Sex hormones; Steroid hormones; Viruses.

Figure 1

Distribution of TTV⁻ and TTV⁺ post-MP women (A) and men (B) relative to pre-MP women, and post-MP relative to men (C). Numbers in graphs indicate n values. Statistics tables below each graph show the respective relative risks (RR) and odds ratios (OR) following Fisher's exact test. No significance could be detected.

Figure 2

TSH-levels in TTV⁻ (Neg, n = 14) and TTV⁺ (Pos, n = 3) pre-MP women, divided by phase of the menstrual cycle. Of the three TTV⁺, one was anovulatory, one hypothyroid with normal ovulation and one both anovulatory and hypothyroid. None of the TTV⁻ were hypothyroid. Hypothyroidism was defined by TSH >3.5 mU/L at one or more occasions.

Figure 3

Levels of progesterone (mid-luteal phase) and LH (ovulatory phase) in TTV⁺ (n = 3) and TTV⁻ (n = 14) pre-MP women. Standard deviation is shown in error bars. The average S-progesterone levels (A) were significantly different in a two-tailed Student's t-test, using Welch's correction (p = 0.002, t = 3.989, Df = 12.53). Difference in average S-LH were not statistically significant (p = 0,156, t = 1.5937, Df = 6.874).