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PLoS By Category | Recent PLoS Articles
Obstetrics

Genome-Wide Gene Expression Analysis Implicates the Immune Response and Lymphangiogenesis in the Pathogenesis of Fetal Chylothorax
Published: Wednesday, April 18, 2012
Author: Chen-Hsiang Yeang et al.

by Chen-Hsiang Yeang, Gwo-Chin Ma, Jin-Chung Shih, Yu-Shih Yang, Chih-Ping Chen, Shun-Ping Chang, Sheng-Hai Wu, Chin-San Liu, Shou-Jen Kuo, Hung-Chieh Chou, Wuh-Liang Hwu, Alan D. Cameron, Norman A. Ginsberg, Yi-Shing Lin, Ming Chen

Fetal chylothorax (FC) is a rare condition characterized by lymphocyte-rich pleural effusion. Although its pathogenesis remains elusive, it may involve inflammation, since there are increased concentrations of proinflammatory mediators in pleural fluids. Only a few hereditary lymphedema-associated gene loci, e.g. VEGFR3, ITGA9 and PTPN11, were detected in human fetuses with this condition; these cases had a poorer prognosis, due to defective lymphangiogenesis. In the present study, genome-wide gene expression analysis was conducted, comparing pleural and ascitic fluids in three hydropic fetuses, one with and two without the ITGA9 mutation. One fetus (the index case), from a dizygotic pregnancy (the cotwin was unaffected), received antenatal OK-432 pleurodesis and survived beyond the neonatal stage, despite having the ITGA9 mutation. Genes and pathways involved in the immune response were universally up-regulated in fetal pleural fluids compared to those in ascitic fluids. Furthermore, genes involved in the lymphangiogenesis pathway were down-regulated in fetal pleural fluids (compared to ascitic fluid), but following OK-432 pleurodesis, they were up-regulated. Expression of ITGA9 was concordant with overall trends of lymphangiogenesis. In conclusion, we inferred that both the immune response and lymphangiogenesis were implicated in the pathogenesis of fetal chylothorax. Furthermore, genome-wide gene expression microarray analysis may facilitate personalized medicine by selecting the most appropriate treatment, according to the specific circumstances of the patient, for this rare, but heterogeneous disease.
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