Genome-Wide Gene Expression Analysis Implicates the Immune Response and Lymphangiogenesis in the Pathogenesis of Fetal Chylothorax

Autor: Sheng-Hai Wu, AD Cameron, Shun-Ping Chang, Wuh-Liang Hwu, Hung-Chieh Chou, Ming Chen, Jin-Chung Shih, Shou-Jen Kuo, Chen-Hsiang Yeang, Norman A. Ginsberg, Yi-Shing Lin, Yu Shih Yang, Chin-San Liu, Chih-Ping Chen, Gwo-Chin Ma
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Genetic Screens
Integrins
Pleural effusion
Microarrays
medicine.medical_treatment
lcsh:Medicine
Protein Tyrosine Phosphatase
Non-Receptor Type 11
Chylothorax
Pathogenesis
Autosomal Recessive
Pregnancy
Lymphangiogenesis
lcsh:Science
Regulation of gene expression
Multidisciplinary
Obstetrics and Gynecology
Forkhead Transcription Factors
Genomics
Fetal Diseases
Medicine
Female
Research Article
Test Evaluation
Genotype
Clinical Research Design
Genetic Counseling
Biology
Ultrasonography
Prenatal
Genome Analysis Tools
Diagnostic Medicine
medicine
Genome-Wide Association Studies
Humans
Genetic Testing
Management of High-Risk Pregnancies
Clinical Genetics
Fetus
Gene Expression Profiling
lcsh:R
Personalized Medicine
Computational Biology
medicine.disease
Vascular Endothelial Growth Factor Receptor-3
Gene expression profiling
Gene Expression Regulation
Case-Control Studies
Immunology
Mutation
lcsh:Q
Genome Expression Analysis
Pleurodesis
Genome-Wide Association Study
Zdroj: PLoS ONE
PLoS ONE, Vol 7, Iss 4, p e34901 (2012)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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