Salivary Telomere Length and Lung Function in Adolescents Born Very Preterm: A Prospective Multicenter Study

<div><p>Preterm birth is associated with abnormal respiratory functions throughout life. The mechanisms underlying these long-term consequences are still unclear. Shortening of telomeres was associated with many conditions, such as chronic obstructive pulmonary disease. We aimed to search for an association between telomere length and lung function in adolescents born preterm. Lung function and telomere length were measured in 236 adolescents born preterm and 38 born full-term from the longitudinal EPIPAGE cohort. Associations between telomere length and spirometric indices were tested in univariate and multivariate models accounting for confounding factors in the study population. Airflows were significantly lower in adolescents born preterm than controls; forced expiratory volume in one second was 12% lower in the extremely preterm born group than controls (p<0.001). Lower birth weight, bronchopulmonary dysplasia and postnatal sepsis were significantly associated with lower airflow values. Gender was the only factor that was significantly associated with telomere length. Telomere length correlated with forced expiratory flow 25–75 in the extremely preterm adolescent group in univariate and multivariate analyses (p = 0.01 and p = 0.02, respectively). We evidenced an association between telomere length and abnormal airflow in a population of adolescents born extremely preterm. There was no evident association with perinatal events. This suggests other involved factors, such as a continuing airway oxidative stress leading to persistent inflammation and altered lung function, ultimately increasing susceptibility to chronic obstructive pulmonary disease.</p></div

LFT and telomere length according to group of gestational age.

<p>Continuous variables are shown as medians [IQR] and categorical variables are shown as numbers (%).</p><p>*Comparison between the 24–28 wPMA, 29–32 wPMA and 39–40 wPMA groups with chi-square test or Kruskal-Wallis test, as appropriate.</p><p>†Compared to the normal control group (Z-score ≥ -1.64)</p><p>LFT and telomere length according to group of gestational age.</p

Telomere length and lung function parameters in ex-preterm adolescents.

<p>Telomere length and lung function parameters in ex-preterm adolescents.</p

Flowchart of the study population.

<p>For each group, age at the time of the study is expressed as medians [IQR]. *probable move without leaving a forwarding address. LFT: lung function tests; QC: quality control; qPCR: quantitative polymerase chain reaction; wPMA: weeks of post-menstrual age.</p

Epidemiological and clinical characteristics of the study population.

<p>Continuous variables are expressed as medians [IQR] and categorical variables as numbers (%).</p><p>NA: not available data</p><p>Epidemiological and clinical characteristics of the study population.</p

Telomere length and lung function parameters before and after adjustment for potential confounders.

<p>*Coefficient for an increase of 0.1 in telomere length</p><p>Adjustment for birth weight, BPD, sex, postnatal sepsis and maternal cigarette smoking during pregnancy</p><p>Telomere length and lung function parameters before and after adjustment for potential confounders.</p

Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors.

The natural killer (NK) cell receptor NKp30 is involved in the recognition of tumor and dendritic cells (DCs). Here we describe the influence of three NKp30 splice variants on the prognosis of gastrointestinal sarcoma (GIST), a malignancy that expresses NKp30 ligands and that is treated with NK-stimulatory KIT tyrosine kinase inhibitors. Healthy individuals and those with GIST show distinct patterns of transcription of functionally different NKp30 isoforms. In a retrospective analysis of 80 individuals with GIST, predominant expression of the immunosuppressive NKp30c isoform (over the immunostimulatory NKp30a and NKp30b isoforms) was associated with reduced survival of subjects, decreased NKp30-dependent tumor necrosis factor-\u3b1 (TNF-\u3b1) and CD107a release, and defective interferon-\u3b3 (IFN-\u3b3) and interleukin-12 (IL-12) secretion in the NK-DC cross-talk that could be restored by blocking of IL-10. Preferential NKp30c expression resulted partly from a single-nucleotide polymorphism at position 3790 in the 3' untranslated region of the gene encoding NKp30. The genetically determined NKp30 status predicts the clinical outcomes of individuals with GIST independently from KIT mutation