The placental immunomodulatory cytokine regeneration and tolerance factor is also expressed by both human cycling and early pregnant endometrium

Problem: Regeneration and tolerance factor (RTF) has been recently suggested to contribute to the control of fetal-ablating immunity at the maternal-fetal interface through the induction of T helper 2 (Th2)-dominated response. The protein consists of a membrane-associated domain and an extracellular portion which is proteolitically cleaved to yield a soluble peptide. In humans, it has been shown to be expressed by invading cytotrophoblasts and decidual lymphoid cells, to be increased on peripheral blood B lymphocytes during a normal gestation and on circulating natural killer cells during unsuccessful pregnancies. However, the expression of RTF in other cell types and, specifically, in non-hematopoietic maternal cells of the human uterus has not been characterized in detail. Thus, we have specifically studied the expression and modulation of the cytokine in human endometrium obtained in different phases of the cycle and in early pregnancy. Methods: The 20 kDa extracellular domain of RTF has been localized by immunohistochemical method and Western blot analysis. Levels of RTF messenger RNA (mRNA) in basal and stimulated conditions have been evaluated by semiquantitative reverse transcription-polymerase chain reaction. Results: The extracellular domain of RTF could be detected in both the glandular epithelium and stroma with diffuse distribution in both cycling endometrium and first trimester decidua. Both cycling and pregnant endometrium expressed the gene for RTF but mRNA levels resulted significantly increased in secretory phase-endometrial stromal cells when compared to proliferative phase samples. Inflammatory cytokines, interleukin-1\u3b2 and tumour necrosis factor \u3b1 were able to directly increase endometrial RTF mRNA expression. Conclusion: These results indicate that RTF is constitutively expressed at endometrial and decidual level and its up-regulation during the secretory phase of the cycle may be relevant in mediating some immune-related aspects of uterine physiology

Down's syndrome screening: a controversial test, with more controversy to come!

By 1998, most health authorities offered antenatal screening for Down's syndrome, usually by biochemical methods. To date, the development of this form of screening has not been coordinated by a national body and, consequently, there are wide variations in practice between localities. Fortunately, many of these variations have not led to any noticeable inequality of health provision, but the wide variation in risk cut offs used by different centres does. Other variations merely lead to potentially unnecessary expenditure; whereas it is believed that adding extra tests to the screening procedure is beneficial (such as double test to triple test), statistical evaluation of the confidence intervals for the detection rates quoted indicates that there is no evidence that the extra test provides an increase in detection. The cervical screening programme has progressively improved, partly through the auspices of a national framework. A similar national approach would benefit Down's screening and is only now being considered: the national screening committee (NSC) is currently drafting recommendations. To ensure optimum screening performance, the NSC should specify the risk thresholds applied, the screening protocols to be used—that is, an opt-in programme with a minimum (possibly even a maximum) of two biochemical analytes or a nuchal fold evaluation—and perhaps should even recommend national population parameters to be used for risk calculation. It might even be advisable for statistical work to be carried out to determine whether local derivation of medians is truly necessary. Furthermore, defined options for older women could be specified—for example, should all older patients have the option to proceed directly to amniocentesis if they wish or should National Health Service amniocentesis only be available for those with a "high risk" screening result. The difficulties that will face the NSC in deciding which screening policy to adopt are also considered; specifically, the lack of evidence to suggest that triple testing is superior to double testing, and the lack of evidence to prove the superiority of one analyte over another. This inadequacy of evidence is not from want of trying, but is caused by the problems of collecting enough data to provide statistical significance. Finally, there is one important difference between cervical and Down's syndrome screening that has a major impact on the advice given by any "expert"; namely, patents. Many aspects of Down's screening are subject to patents and, therefore, there is more potential for apparently uncontroversial decisions to rebound with future retrospective patent infringement claims. Thus, it would be sensible to insist that any member of a national body deciding upon Down's screening policy must fully disclose all potential conflicts of interest, both personal and family, before they are allowed to sit on the committee. Furthermore, if a national policy is decided upon, worldwide patent searches should be carried out to determine whether there are any possible unforeseen legal consequences of any recommendation. Key Words: trisomy 21 • screening • nuchal fol