Proteolysis of insulin-like growth factor-binding protein-3 in human immunodeficiency virus-positive children who fail to thrive.
Failure to thrive is a common manifestation of human immunodeficiency virus (HIV) infection in children. Given the role of insulin-like growth factor I (IGF-I) in stimulating postnatal growth, we have examined whether HIV-infected pediatric patients with growth failure have lower serum concentrations of IGF-I than age-matched control subjects. IGF-I was measured in 16 HIV-infected children and 13 HIV-negative controls. Ten of the HIV-infected children failed to thrive based on height and linear growth that was below the National Center for Health Statistics 10th percentile. IGF-I levels were significantly lower in children who failed to thrive compared to those in age-matched controls (20 vs. 60 micrograms/L; P < 0.001). Children who failed to thrive also displayed lower IGF-I levels than HIV-positive children, who exhibited normal growth velocity (20 vs. 91 micrograms/L; P < 0.001). Failure to thrive was associated with a significant reduction in circulating levels of IGF-binding protein-3 (IGFBP-3), as determined by ligand and Western blotting (P < 0.001), enhanced IGFBP-3 proteolysis (P < 0.001), and a decrease in the serum concentration of the acid-labile subunit of the IGFBP-3 ternary complex (P < 0.005). IGFBP-3 proteolysis was negatively correlated with IGF-I (r = 0.78) and IGFBP-3 levels (r = 0.70). Failure to thrive was associated with a reduction in the formation of the ternary complex, but the ternary complex could be restored by the addition of an excess of IGFBP-3 to serum. These results indicate that low levels of IGF-I, IGFBP-3, and acid-labile subunit are associated with a failure to thrive in HIV-infected children.
Frost
R A
RA
Department of Medicine, State University of New York, Stony Brook 11794, USA.
Nachman
S A
SA
Lang
C H
CH
Gelato
M C
MC
D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D004591:Electrophoresis, Polyacrylamide Gel; D005183:Failure to Thrive / Q000209:etiology*; D006679:HIV Seropositivity / Q000150:complications* / Q000378:metabolism*; D006801:Humans; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000737:chemistry / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D010447:Peptide Hydrolases