Altered glycosylation patterns of ApoE in pre-eclampsia
Evaluation of: Atkinson KR, Blumenstein M, Black MA et al.: An altered pattern of circulating apolipoprotein E3 isoforms is implicated in preeclampsia. J. Lipid Res. (2008) (Epub ahead of print) – Dulay
Despite enormous efforts at unraveling the etiology of pre-eclampsia, it still remains a mystery. One theory behind the underpinnings of the disease lies in the concept of aberrant lipid abnormalities, similar to those noted in atherosclerosis. Endothelial dysfunction is a well-accepted observation with regard to pre-eclampsia, and it is possible that lipid dysfunction may play a role in the disease process. The idea of protein dysregulation and proteomic analysis has been critical in understanding protein structure and function, and in identifying possible disease biomarkers, especially in pre-eclampsia. A recent study from The Journal of Lipid Research utilized 2D gel-based proteomic approaches such as 2D electrophoresis and difference gel electrophoresis analysis of serum and plasma, respectively, from women presenting with pre-eclampsia at 36–38 weeks (n = 12) and gestational-age matched healthy controls (n = 12). Bioinformatic analysis identified several serum/plasma biomarker candidates in women diagnosed with pre-eclampsia; specifically, altered glycosylation of circulating ApoE isoforms. This novel finding helps to elucidate the relationship between the development of pre-eclampsia and, later on, cardiovascular disease. Future studies should involve analysis of these potential biomarkers in better-defined groups that provide further distinction between mild and severe pre-eclampsia, and chronic hypertension without pre-eclampsia during pregnancy. Additionally, attention should be given towards the correlation of the different glyco-isoforms with disease severity and outcome.
Study reports microRNA profiles can be reliably analyzed from serum samples
Evaluation of: Gilad S, Meiri E, Yogev Y et al.: Serum microRNAs are promising novel biomarkers. PLoS ONE 3, e3148 (2008) – Buhimschi
MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs that function as gene regulators. miRNAs participate in many essential biological processes, such as cell proliferation, differentiation, apoptosis, metabolism, stress and oncogenesis, although their individual roles are just beginning to unravel. Gene-expression profiling studies of various cancers have revealed that the pattern of miRNA expression varies markedly across different tumors, and that a small number of miRNAs define cancer better than expression data derived from thousands of mRNAs. Owing to the association between differentially expressed miRNAs and various cancers, miRNAs have emerged as attractive biomarker candidates Citation[1]. Importantly, and unlike mRNA, miRNAs are stable and can be analyzed even in formalin-fixed and paraffin-embedded tissues. A recent study published in PLoS One has sought to determine whether miRNA profiles can also be derived from biological samples obtained noninvasively, such as serum or urine. To validate the biological significance, the authors analyzed miRNA profiles of 30 women (ten nonpregnant and 20 pregnant in either the first or third trimester), and found that miRNAs are present in cell-free bodily fluids and that serum levels of three miRNAs of likely placental origin were significantly higher in the pregnant state. The authors further report that miRNA profiles of serum and urine differed significantly. The next step is to validate the diagnostic value of serum miRNA profiling in larger sample sizes and to explore whether particular combinations of serum miRNA can serve as future diagnostics for pathological pregnancy states.
Reference
- Lu J , GetzG, MiskaEAet al. : MicroRNA expression profiles classify human cancers.Nature435, 834–838(2005).
Advantages, disadvantages and limitations of methodologies for assessment of micronutrient status in pregnant women
Evaluation of: Wheeler S: Assessment and interpretation of micronutrient status during pregnancy. Proc. Nutr. Soc. 67, 437–450 (2008) – Buhimschi
Standard obstetric practice includes screening for anemia in pregnancy and correcting deficiencies, generally by providing iron supplements to anemic patients. However, pregnancy is a time of vast changes in maternal physiology, which influences micronutrient levels and values of indicators that are generally used to screen for anemia in nonpregnant subjects. A review article published recently in Proceedings of the Nutrition Society discusses current methodologies used to assess anemia in pregnancy, with particular focus on the assessment of iron, folate and vitamin B12. The study concludes that sensitivity and specificity of virtually all biomarkers is reduced, especially at term, and that many of the normal ranges commonly used for nonpregnant and nonlactating subjects may be inappropriate. A future direction is to prioritize studies aimed at validating iron and, especially, folate status in pregnant women, and to establish correct normative values for micronutrient status in pregnant women. Furthermore, newer methodologies that are able to measure specific folate species with higher precision and in larger sample sizes should be explored.
Possible mechanism of the early Th2 bias in neonatal immunity revealed
Evaluation of: Lee HH, Hoeman CM, Hardaway JC et al.: Delayed maturation of an IL-12-producing dendritic cell subset explains the early Th2 bias in neonatal immunity. J. Exp. Med. 205, 2269–2280 (2008) – Huang
Neonates are susceptible to microbial infections and allergic reactions owing to lack of T helper (Th)1 immunity and skewing of the Th2 response. However, the factors responsible for Th2 bias are not well understood. Studies indicate that, although neonates develop both Th1 and -2 cells at the first antigen encounter, at the second antigen encounter a preferential cell apoptotic phenomenon of Th1 cells occurs. This phenomenon is thought to be driven by IL-4 produced by Th2 counterparts Citation[1]. A recent report in The Journal of Experimental Medicine implicated the delayed maturation of IL-12-producing dendritic cells in the setting of the Th2-bias characteristic of neonatal immunity. IL-12 family proteins are differentially expressed by subsets of dendritic cells, and play important roles in the deviation of the Th1/2 immune response. Using experimental mouse models, investigators demonstrated that the transition from a preferential Th2 to a Th1 response at day 6 after birth is caused by an acquired ability of the newborn to produce IL-12 that, in turn, downregulates IL-13 receptor α1 and rescues Th1 immunity from IL-4-induced apoptosis. Future studies need to determine the possible involvement of other IL-12 family members, such as IL-23 and -27, in rescuing Th1 responses. Moreover, the roles of macrophages and additional subsets of dendritic cells other than the CD8α+CD4- subtype in Th1/2 polarization need to be investigated to provide further insight into the development of novel preventive and therapeutic strategies against allergies in children.
Reference
- Li L , LeeHH, BellJJet al. : IL-4 utilizes an alternative receptor to drive apoptosis of Th1 cells and skews neonatal immunity toward Th2.Immunity20, 429–440(2004).