A proteomic approach identified growth hormone-dependent nutrition markers in children with idiopathic short stature

Gunnel Hellgren,Ze'Ev Hochberg,Jovanna Dahlgren,Andreas Fm Nierop,Björn Andersson,Kerstin Albertsson-Wikland

doi:10.1186/1477-5956-6-35

Abstract

BackgroundThe broad range in growth observed in short prepubertal children receiving the same growth hormone (GH) dose is due to individual variation in GH responsiveness. This study used a pharmaco-proteomic approach in order to identify novel biomarkers that discriminate between short non-GH-deficient (GHD) children who show a good or poor growth response to GH treatment.A group of 32 prepubertal children with idiopathic short stature (ISS) were included in the study. Children were classified on the basis of their first year growth velocity as either good (high responders, n = 13; range, 0.9–1.3 standard deviation score (SDS) or poor (low responders, n = 19; range, 0.3–0.5 SDS) responders to GH treatment (33 μg/kg daily).Serum protein expression profiles before, and after 1 year of GH treatment, were analyzed on a weak cationic exchange array (CM10) using surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF-MS).ResultsChanges in the intensity of two protein peaks (13.788 kDa and 17.139 kD) during the study period allowed the correct classification of 82% of children as high and low responders, respectively. The 13.788 kD peak, transthyretin, decreased in the high-responder group and increased in the low-responder group during 1 year of GH treatment, whereas the 17.139 kDa peak, apolipoprotein A-II (Apo A-II) decreased in the high-responder group and remained unchanged in the low-responder group. These peaks were identified by the consistency of peak pattern in the spectra, serum depletion experiments using specific antibodies and mass spectrometry.ConclusionOur results suggest that transthyretin and apolipoprotein A-II may have a role in GH sensitivity and could be used as markers to predict which short prepubertal children with ISS will show a good or poor response to GH treatment.

Highlights

The broad range in growth observed in short prepubertal children receiving the same growth hormone (GH) dose is due to individual variation in GH responsiveness
Our results suggest that transthyretin and apolipoprotein A-II may have a role in GH sensitivity and could be used as markers to predict which short prepubertal children with idiopathic short stature (ISS) will show a good or poor response to GH treatment
For a number of the peaks identified, we found that the change in peak intensity during the first year of treatment correlated with GH responsiveness

Summary

Introduction

The broad range in growth observed in short prepubertal children receiving the same growth hormone (GH) dose is due to individual variation in GH responsiveness. This study used a pharmaco-proteomic approach in order to identify novel biomarkers that discriminate between short non-GH-deficient (GHD) children who show a good or poor growth response to GH treatment. The left panels demonstrate which peaks are selected and the degree to which they correlate with the first dimension (low/high response on the xaxis). In the sense that it has no correlation with the response variable and, component, in the sense that it of all the selected predictor variables it explains the maximum variance. The use of this dimension facilitates the discovery of clusters of related peaks, or peaks conveying comparable information.

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Discussion

Conclusion