Human leukocyte antigen (HLA)-G during pregnancy part I: correlations between maternal soluble HLA-G at midterm, at term, and umbilical cord blood soluble HLA-G at term.

Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on trophoblast cells and has been proposed to have immunomodulatory functions during pregnancy. Soluble HLA-G1 (sHLA-G1) can be generated by the shedding of membrane-bound HLA-G molecules; however, three soluble isoforms also exist (HLA-G5 to -G6). During pregnancy, it is unknown whether there is a correlation between sHLA-G levels in maternal and fetal blood. In 246 pregnancies, we have measured the levels of sHLA-G1/-G5 in maternal blood plasma samples from gestational week 20 (GW20) and at term, as well as in umbilical cord blood samples. Soluble HLA-G levels declined by 38.4% in maternal blood from GW20 to term, and sHLA-G levels were significantly lower in maternal blood at term than in GW20 (P<0.001). At term, the sHLA-G levels were significantly higher in maternal blood than in umbilical blood (P<0.001). HLA-G levels in maternal blood in GW20 and at term, and in maternal blood at term and umbilical cord blood, were correlated (P<0.001 and P<0.01, respectively). This is the first large study simultaneously measuring sHLA-G in both maternal and umbilical cord blood. The finding that sHLA-G levels are significantly lower in fetal compared with maternal blood at term documents for the first time that sHLA-G is not freely transferred over the placental barrier. Soluble HLA-G levels in maternal and fetal blood were found to be correlated, which may be due to shared genetic factors of importance for production of sHLA-G in the mother and child, or it may support the theory that sHLA-G in the pregnant woman and the fetus is partly derived from a "shared organ", the placenta.

Human leukocyte antigen (HLA)-G during pregnancy part II: associations between maternal and fetal HLA-G genotypes and soluble HLA-G.

Human leukocyte antigen (HLA)-G is a class Ib molecule with restricted tissue distribution expressed on the extra-villous trophoblast and seems to have immunomodulatory functions during pregnancy. Studies have linked HLA-G polymorphisms to pregnancy complications such as preeclampsia and recurrent miscarriage. Levels of soluble HLA-G (sHLA-G) in blood plasma from non-pregnant donors seem to be associated with these polymorphisms. In the current study, we have genotyped 246 mothers and their offspring for HLA-G polymorphisms in the 3'-untranslated region (3'UTR) and measured sHLA-G in maternal blood plasma samples from gestational week 20 and at term, as well as in fetal umbilical cord blood samples. This is the first large study simultaneously performing HLA-G genotyping of mother and offspring and measuring sHLA-G in both maternal and umbilical cord blood. The results showed that increasing numbers of 14bp ins (rs66554220) alleles in the mother-child genotype combinations were associated with higher maternal sHLA-G levels at term when restricting the analysis to 14bp ins/del heterozygous mothers (p=0.015). Furthermore, increasing numbers of 14InsG haplotypes (14bp ins/del and +3142C/G (rs1063320) polymorphism) in mother-child genotype combinations were associated with higher levels of sHLA-G at term in heterozygous 14DelC/14InsG mothers (p=0.005). In conclusion, the results indicate that there is an association between combined feto-maternal HLA-G genotypes and sHLA-G levels in maternal blood plasma.

Plasma TNF-α levels are higher in early pregnancy in patients with secondary compared with primary recurrent miscarriage.

PROBLEM: Specific pro-inflammatory cytokine profiles in plasma may characterize women with recurrent miscarriage (RM) but the dynamics of the cytokine profiles with progressing pregnancy is largely unknown. METHOD OF STUDY: Plasma was repeatedly sampled in the first trimester from 47 RM patients. The concentrations of five cytokines including tumour necrosis factor alpha (TNF-α) were measured. TNF-α levels were correlated to carriage of five TNFA promoter polymorphisms. RESULTS: TNF-α levels increased (P = 0.014) with progressing pregnancy, with higher levels in secondary than primary RM (P = 0.042) but with no significant impact on outcome. Carriage of TNFA -863C and TNFA -1031T was associated with higher TNF-α levels, and the former was found more often in secondary than primary RM (P < 0.02). CONCLUSION: Plasma TNF-α levels increase during early pregnancy in RM women regardless of outcome, but are higher in secondary than primary RM, which may be partly genetically determined.

Influence of environmental factors on facial ageing.

BACKGROUND: A recent twin study has shown that 'looking old for one's age' is associated with increased mortality. Approximately 40% of the variation in perceived age is due to non-genetic factors. OBJECTIVE: To examine environmental factors influencing perceived age controlling for diseases. DESIGN: A twin study. SETTING: In the 2001 wave of the population-based survey--the Longitudinal Study of Aging Danish Twins--participants provided information on a wide range of exposures and health indicators. Additionally, they were asked to have a face photograph taken. SUBJECTS: A total of 1826 elderly (70+) twins who had a high-quality face photograph taken. METHODS: Ten nurses assessed the visual age of each twin from the face photograph. The mean of the nurses' age estimates for each twin was used as the twin's perceived age. Multivariate linear regression and intrapair comparison (for intact twin pairs) were used for analyses. RESULTS: Statistically significant determinants of facial ageing associated with high perceived age for men were smoking (P = 0.01), sun exposure (P = 0.02) and low body mass index (BMI) (P<0.005), while for women they were low BMI (P = 0.05) and low social class (P<0.005). The number of children (men) and marital status (P = 0.08) and depression symptomatology score (women) were borderline significantly associated with facial ageing. CONCLUSION: Our study confirms previous findings of a negative influence of sun exposure, smoking and a low BMI on facial ageing. Furthermore, our study indicates that high social status, low depression score and being married are associated with a younger look, but the strength of the associations varies between genders.