A potential biomarker in the cord blood of preterm infants who develop retinopathy of prematurity.
Preterm infants are at risk of developing sepsis, necrotizing enterocolitis (NEC), chronic lung disease (CLD), and retinopathy of prematurity (ROP). We used high-throughput mass spectrometry to investigate whether cord blood proteins can be used to predict development of these morbidities. Cord blood plasma from 44 infants with a birth weight of <1500 g was analyzed by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF). Six infants developed ROP >or=stage II, 10 CLD, three sepsis, and one NEC. We detected 814 protein signals representing 330 distinct protein species. Nineteen biomarkers were associated with development of >or=stage II ROP [false-discovery rate (FDR) <5%] and none with CLD. Several proteins with molecular weight (Mr) 15-16 kD and pI 4-5 were detected with increased abundance in infants with ROP, while similar Mr proteins with pI 7-9 were less abundant in these patients. Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and sequence analysis identified these proteins as alpha-, beta-, and gamma-globin chains. Partial deamidation of Asn139 in beta-globin chains was observed only in the pI 4-5 proteins. We conclude that there are several promising biomarkers for the risk of ROP. Deamidation of globin chains is especially promising and may indicate underlying prenatal pathologic mechanisms in ROP. Validation studies will be undertaken to determine their clinical utility.
Madan
Ashima
A
Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California 94304, USA. ashima@stanford.edu
El-Ferzli
George
G
Carlson
Scott M
SM
Whitin
John C
JC
Schilling
James
J
Najmi
Amir
A
Yu
Tom To-Sang
TT
Lau
Kenneth
K
Dimmitt
Reed A
RA
Cohen
Harvey J
HJ
D015415:Biomarkers / Q000032:analysis; D020345:Enterocolitis, Necrotizing / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000737:chemistry* / Q000378:metabolism; D005865:Gestational Age; D005914:Globins / Q000032:analysis*; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007234:Infant, Premature; D008171:Lung Diseases / Q000378:metabolism; D008297:Male; D012178:Retinopathy of Prematurity / Q000175:diagnosis*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D015415:Biomarkers; D005914:Globins