An immune window of opportunity to prevent spontaneous abortion: prepregnancy peripheral leukocytes and subsets were associated with a decreased risk of spontaneous abortion.

STUDY QUESTION: Do prepregnancy peripheral leukocytes (PPLs) and their subsets influence the risk of spontaneous abortion (SAB)? SUMMARY ANSWER: PPLs and their subsets are associated with the risk of SAB. WHAT IS KNOWN ALREADY: Compelling studies have revealed the crucial role of maternal peripheral leukocytes in embryo implantation and pregnancy maintenance. Adaptive changes are made by PPLs and their subsets after conception. STUDY DESIGN, SIZE, DURATION: This population-based retrospective cohort study was based on data from the National Free Pre-pregnancy Check-up Project (NFPCP) in mainland China. Couples preparing for pregnancy within the next six months were provided with free prepregnancy health examinations and counseling services for reproductive health. The current study was based on 1 310 494 female NFPCP participants aged 20-49 who became pregnant in 2016. After sequentially excluding 235 456 participants lost to follow-up, with multiple births, and who failed to complete blood tests, a total of 1 075 038 participants were included in the primary analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: PPLs and their subset counts and ratios were measured. The main outcome was SAB. A multivariable logistic regression model was used to estimate the odds ratio (OR) and 95% CI of SAB associated with PPLs and their subsets, and restricted cubic spline (RCS) was used to estimate the nonlinear exposure-response relationship. MAIN RESULTS AND ROLE OF CHANCE: Of the included pregnant participants, a total of 35 529 SAB events (3.30%) were recorded. Compared to participants with reference values of PPLs, the ORs (95% CIs) of leukopenia and leukocytosis for SAB were 1.14 (1.09-1.20) and 0.74 (0.69-0.79), respectively. The RCS result revealed a monotonous decreasing trend (Pnonlinear < 0.05). Similar relationships were observed for the neutrophil count and ratio, monocyte count, and middle-sized cell count and ratio. The lymphocyte ratio showed a positive and nonlinear relationship with the risk of SAB (Pnonlinear < 0.05). Both eosinophils and basophils showed positive relationships with the risk of SAB (eosinophil Pnonlinear > 0.05 and basophil Pnonlinear < 0.05). LIMITATIONS, REASONS FOR CAUTION: Chemical abortion events and the cause of SAB were not collected at follow-up. Whether women with abnormal PPLs had recovered during periconception was not determined. WIDER IMPLICATIONS OF THE FINDINGS: PPLs and their subsets are associated with the risk of SAB. Leukopenia and neutropenia screening in women preparing for pregnancy and developing a feasible PPL stimulation approach should be emphasized to utilize the immune window of opportunity to prevent SAB. STUDY FUNDING/COMPETING INTEREST(S): This study was approved by the Institutional Research Review Board of the National Health and Family Planning Commission. This study was supported by the National Key Research and Development Program of China (grants 2021YFC2700705 [Y.Y.] and 2016YFC100307 [X.M.]) and the National Natural Science Foundation of China (grant no. 82003472 [L.W.]). The funding source was not involved in the study design, data collection, analysis and interpretation of the data, writing the report, or the decision to submit this article for publication. No competing interests. TRIAL REGISTRATION NUMBER: N/A.

The recruitment of peripheral blood leukocytes to the brain is delayed in susceptible BALB/c compared to resistant C57BL/6 mice during herpes simplex virus encephalitis.

The cerebral immune response induced by herpes simplex virus (HSV) encephalitis (HSE) was evaluated in susceptible BALB/c and resistant C57BL/6 mice. BALB/c and C57BL/6 (named C57BL/6-high) mice were respectively infected intranasally with 1 × 103 and 5 × 105 plaque-forming units (PFUs) of HSV-1. C57BL/6 mice (named C57BL/6-low) infected with a low inoculum (1 × 103 PFUs) of HSV-1 were tested in parallel. Mice were monitored for weight loss, sickness signs, and survival for 21 days. The viral load, infectious titers, cytokine/chemokine levels, and peripheral leukocyte infiltration were determined in brain homogenates on days 0 (non-infected), 4, 6, and 8 post-infection (p.i.) by qPCR, plaque assay, ELISA/Luminex™, and flow cytometry, respectively. Our results showed that the mortality of BALB/c mice (67%) was higher compared to those of C57BL/6-low (0%; P ≤ 0.01) and C57BL/6-high (20%; P ≤ 0.05) animals. This higher mortality was associated with increased infectious titers and cytokine/chemokine levels in the brains of BALB/c compared to C57BL/6 mice. Recruitment of inflammatory monocytes, dendritic cells, natural killer, and natural killer T cells to the brain was higher in C57BL/6-high compared to BALB/c animals on day 4 p.i. Infiltration of inflammatory monocytes and T cells in the brain of BALB/c mice was seen on day 6 p.i. Our data suggest that a rapid, sustained, and coordinated recruitment of peripheral leukocytes to the brain of C57BL/6-high mice results in an effective control of viral replication and inflammation whereas the delayed infiltration of immune cells in the brain of BALB/c mice was associated with an exacerbated inflammatory response during HSE.

Associations between Short-Term Air Pollution Exposure and the Peripheral Leukocyte Distribution in the Adult Male Population in Beijing, China.

The inflammatory effects of air pollution exposure may account for increased public health risk. However, evidence regarding the effects of air pollution on peripheral blood leukocytes in the population is inconsistent. We investigated the association between the short-term effects of ambient air pollution and the peripheral blood leukocyte distribution in adult men in Beijing, China. From January 2015 to December 2019, a total of 11,035 men aged 22-45 years in Beijing were included in the study. Their peripheral blood routine parameters were measured. The ambient pollution monitoring parameters (particulate matter ≤ 10 µm (PM10), PM2.5, nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3)) were collected daily. The potential association between ambient air pollution exposure and peripheral blood leukocyte count and classification was analyzed with generalized additive models (GAMs). After adjusting for confounding factors, PM2.5, PM10, SO2, NO2, O3, and CO were significantly correlated with changes to at least one peripheral leukocyte subtype. Short-term and cumulative air pollutant exposure dramatically increased the participants' peripheral blood neutrophil, lymphocyte, and monocyte numbers and decreased eosinophils and basophils. Our results demonstrated that air pollution induced inflammation in the participants. The peripheral leukocyte count and classification can be utilized to evaluate the inflammation induced by air pollution in the exposed male population.

Peripheral Blood Transcripts Predict Preoperative Obstructive Total Anomalous Pulmonary Venous Connection.

The lack of accessible noninvasive tools to examine the molecular alterations limits our understanding of the causes of total anomalous pulmonary venous connection (TAPVC), as well as the identification of effective operational strategies. Here, we consecutively enrolled peripheral leukocyte transcripts of 26 preoperative obstructive and 22 non-obstructive patients with TAPVC. Two-hundred and fifty six differentially expressed mRNA and 27 differentially expressed long noncoding RNA transcripts were dysregulated. The up-regulated mRNA was enriched in the hydrogen peroxide catabolic process, response to mechanical stimulus, neutrophil degranulation, hemostasis, response to bacterium, and the NABA CORE MATRISOME pathway, all of which are associated with the development of fibrosis. Furthermore, we constructed predictive models using multiple machine-learning algorithms and tested the performance in the validation set. The mRNA NR3C2 and lncRNA MEG3 were screened based on multiple iterations. The random forest prediction model can predict preoperative obstruction patients in the validation set with high accuracy (area under curve = 1; sensitivity = 1). These data highlight the potential of peripheral leukocyte transcripts to evaluate obstructive-related pathophysiological alterations, leading to precision healthcare solutions that could improve patient survival after surgery. It also provides a novel direction for the study of preoperative obstructive TAPVC.

Changes in peripheral inflammation-related gene expression by postprandial glycemic response in healthy Japanese men.

OBJECTIVES: Continuous postprandial hyperglycemia is associated with the onset of cardiovascular disease. In recent years, the mRNA expression of inflammation-related genes in peripheral blood leukocytes has been shown to be induced by an increase in blood glucose levels. The aim of this study was to investigate differences in the expression of inflammation-related genes in peripheral blood leukocytes in response to an increase in blood glucose from individuals who consumed two kinds of breakfast meals with different glycemic indexes (GIs). METHODS: Twenty healthy Japanese men 40 to 70 y of age were given low- or high-GI meals for breakfast for 14 d. Clinical examinations were performed on days 7 and 14. Their blood glucose levels and insulin concentrations were measured from before breakfast ingestion to 120 min after. Additionally, using the blood obtained before and 120 min after breakfast, the mRNA expression levels of inflammation-related genes in peripheral leukocytes were measured. RESULTS: The blood glucose levels were significantly lower in the low-GI meal intake group at 30, 60, and 120 min after breakfast than in the high-GI meal intake group. The intake of high-GI meals for 6 d led to an increase in the mRNA levels of interleukin-1ß, S100A4, and CD18 compared with the period of low-GI meals. CONCLUSION: The intake of a low-GI breakfast for 1 wk in healthy Japanese men resulted in lower postprandial blood glucose and insulin levels, which were accompanied by a reduced expression of inflammation-related genes in peripheral blood leukocytes.

Peripheral leukocyte counts vary with lipid levels, age and sex in subjects from the healthy population.

BACKGROUND AND AIMS: Disorders in blood lipid metabolism and leukocyte-mediated inflammation are considered the main mechanisms of the pathogenesis of atherosclerosis. This study aims to show whether and how peripheral leukocyte counts are associated with serum lipid levels. METHODS: This is a cross-sectional study of 175,079 subjects from the healthy population. RESULTS: Age and sex are two key factors dictating the relationship between peripheral leukocyte counts and serum lipid levels. The log-transformed level of triglycerides (LnTG) was positively associated with all leukocyte counts in males except monocyte count in younger subjects. LnTG was positively associated with total leukocyte count in females regardless of age, and it was positively associated with lymphocyte and monocyte counts and neutrophil count only in elderly and young women, respectively. Total cholesterol levels were positively associated with total leukocyte, neutrophil and lymphocyte counts only in young males and with lymphocyte counts only in elderly women. LDL-C was negatively associated with monocyte count in males regardless of age; by contrast, it was positively associated with total leukocyte and lymphocyte counts in females regardless of age range and neutrophil and LnEosinophil counts only in young women. HDL-C was negatively associated with total leukocyte, lymphocyte and monocyte counts in both young men and young women; was negatively associated with monocyte count in elderly men and women; and was negatively associated with LnEosinophil count only in older men. CONCLUSIONS: Peripheral leukocyte counts are extensively associated with serum lipid levels, with patterns differing by sex, age, lipid and leukocyte subset.

Fasting during the suckling-weaning transient period of rats induces inflammatory gene expression in the adipose tissue and peripheral leukocytes.

OBJECTIVE: Nutritional deficiency during developmental stages could be associated with subsequent development of inflammation-related metabolic abnormalities. In this study, we examined the effects of a 3-d fast during the suckling-weaning transient period of rats, and subsequent intake of high-fat-high-sucrose (HF) and low-fat-high-starch (LF) diets in adulthood, on the expression of inflammatory genes in adipose tissue and peripheral leukocytes. METHODS: Male Sprague-Dawley rats were deprived of food for 3 d during the suckling-weaning transient period, and were subsequently fed an HF or LF diet for 14 wk from 17 wk of age. Serum monocyte chemoattractant protein-1 (MCP-1) concentration and mRNA levels of inflammatory genes in mesenteric adipose tissues were assessed at 31 wk of age. The mRNA levels of inflammatory genes at 0 h and 2 h after oral glucose load at 30 wk of age in peripheral leukocytes were measured. RESULTS: Fasting induced circulating MCP-1 protein in rats fed an LF diet but not an HF diet. The HF diet induced high mRNA levels of tumor necrosis factor-α, interleukin-1ß, and S100 proteins in peripheral leukocytes at 2 h after glucose load in fasted rats when compared with controls. Expression of CD11c, an activated macrophage marker, was induced in the fasted group given an HF diet during adulthood. CONCLUSIONS: Fasting rats during the suckling-weaning transient period and an HF diet intake during adulthood enhance inflammation by promoting the expression of inflammatory genes in adipose tissue and peripheral leukocytes.

Peripheral mononuclear leukocyte DNA damage, plasma prolidase activity, and oxidative status in patients with benign prostatic hyperplasia.

OBJECTIVES: Prolidase plays a major role in collagen turnover, matrix remodeling, and cell growth. Benign prostatic hyperplasia (BPH) may be associated with an increased extracellular matrix deposition. Therefore, the present study was designed to investigate the plasma prolidase activity, oxidative status, and peripheral mononuclear leukocyte DNA damage in patients with BPH. PATIENTS AND METHODS: Twenty-six male patients with BPH and 24 healthy male subjects were included in this study. Blood samples were collected from antecubital vein after an overnight fasting period, and the plasma was separated. Plasma prolidase activity, total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) were determined. The peripheral lymphocyte oxidative DNA damage was determined using an alkaline single cell gel electrophoresis assay (comet assay). RESULTS: The plasma prolidase activity, TOS levels, OSI values, and peripheral mononuclear leukocyte DNA damage were significantly higher (P < 0.001), while the TAC levels were significantly lower (P < 0.001) in patients with BPH than controls. In BPH patients, the prolidase activity was significantly associated with TAC levels (r = -0.366, P < 0.05), TOS levels (r = 0.573, P < 0.001), and OSI (r = 0.618, P < 0.001) and peripheral mononuclear leukocyte DNA damage (r = 0.461, P < 0.001). CONCLUSIONS: Our results showed that BPH might be associated with an increased oxidative stress, and also an increased plasma prolidase activity. Increased prolidase activity might play an important role in the etiopathogenesis and/or progression of BPH.

Leukocyte telomere length and prevalence of age-related diseases in semisupercentenarians, centenarians and centenarians' offspring.

Centenarians and their offspring are increasingly considered a useful model to study and characterize the mechanisms underlying healthy aging and longevity. The aim of this project is to compare the prevalence of age-related diseases and telomere length (TL), a marker of biological age and mortality, across five groups of subjects: semisupercentenarians (SSCENT) (105-109years old), centenarians (CENT) (100-104years old), centenarians' offspring (CO), age- and gender-matched offspring of parents who both died at an age in line with life expectancy (CT) and age- and gender-matched offspring of both non-long-lived parents (NLO). Information was collected on lifestyle, past and current diseases, medical history and medication use. SSCENT displayed a lower prevalence of acute myocardial infarction (p=0.027), angina (p=0.016) and depression (p=0.021) relative to CENT. CO appeared to be healthier compared to CT who, in turn, displayed a lower prevalence of both arrhythmia (p=0.034) and hypertension (p=0.046) than NLO, characterized by the lowest parental longevity. Interestingly, CO and SSCENT exhibited the longest (p<0.001) and the shortest (p<0.001) telomeres respectively while CENT showed no difference in TL compared to the younger CT and NLO. Our results strengthen the hypothesis that the longevity of parents may influence the health status of their offspring. Moreover, our data also suggest that both CENT and their offspring may be characterized by a better TL maintenance which, in turn, may contribute to their longevity and healthy aging. The observation that SSCENT showed considerable shorter telomeres compared to CENT may suggest a progressive impairment of TL maintenance mechanisms over the transition from centenarian to semisupercentenarian age.