Fetal Nucleic Acids in Maternal Body Fluids

Abstract

Our laboratory continues to be actively involved in the development of new biomarkers for prenatal diagnosis using maternal blood and amniotic fluid. We have also developed a mouse model that demonstrates that cell-free fetal (cff) DNA is detectable in the pregnant maternal mouse. In human maternal plasma and serum we have analyzed factors that are important in the clinical interpretation of cff DNA levels. Maternal race, parity, and type of conception (natural or assisted) do not affect cff DNA levels, but maternal weight does. We have also analyzed the relationship between placental volume, using a three-dimensionsal ultrasound examination, and cff DNA levels. Surprisingly, there is no association between these values. Finally, we are using specific disease models (such as congenital diaphragmatic hernia and twin-to-twin transfusion) to understand the effects of gestational age and specific pathology on fetal gene expression by analyzing cell-free mRNA levels in maternal plasma. In the amniotic fluid we have focused on improvements in recovery of cff DNA and mRNA. By optimizing recovery we have made some interesting observations about differences in fetal DNA between blood and amniotic fluid. In addition, we have successfully hybridized cff DNA in amniotic fluid to DNA microarrays, permitting assessment of fetal molecular karyotype. We also have preliminary data on fetal gene expression in amniotic fluid. Finally, we remain actively involved in promoting noninvasive prenatal testing in the United States, such as encouraging the use of fetal DNA for fetal rhesus D assessment. On the other hand, we are cautious and concerned about the accuracy of "at-home" kits for fetal gender detection.

Body fluid derived exosomes as a novel template for clinical diagnostics

“…Additionally, cell-free fetal DNA and RNA have been isolated from other body fluids e.g. maternal plasma [27], amniotic fluid [28], and cerebrospinal fluid [29]. Although not tested at that time, it is quite likely that these nucleic acids are associated with microvesicles which could explain their relative stability in the nuclease-rich environment of body fluids.…”

Antinuclear antibodies in healthy people and non-rheumatic diseases – diagnostic and clinical implications

“…During the course of pregnancy, extensive exposure to nuclear antigens may occur. In addition, there is an increase in inflammatory activity that may also affect the immune response [ 37 , 38 ].…”

Antinuclear antibodies in healthy people: the tip of autoimmunity's iceberg?

“…In the future, consideration of the role of pregnancy in ANA reactivity seems worth-while since, during normal pregnancy, there can be extensive exposure to nuclear antigens. Furthermore, although often considered a time of immunosuppression, pregnancy actually shows a surge of inflammatory activity that could impact on immune responsiveness [9,10]. …”