Proteomics of sickle cell disease and sickle cell-associated pulmonary hypertension

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NHLBI	PROTEOM-8

Authors

• S Yuditskaya
• GJ Kato

Abstract

We embarked on a search for biomarkers of sickle cell disease (SCD) and SCD-associated pulmonary hypertension (PH) by an exploratory proteomic approach. A proteomic profiling screen was performed on baseline plasma from 27 SCD patients with PH, 28 without PH, and 25 healthy African-American controls, using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. As we previously reported, multiple uni- and multivariate- statistical analyses of data thus generated, consistently showed lower abundance of a 28.1-kDa peak in SCD patients with PH. Its identity as apolipoprotein A-I (apoA-I) and its utility as a biomarker for SCD-associated PH were successfully validated with high-resolution mass spectrometry, clinical nephelometry assay, and physiologically, as indicated by blunted vasoreactivity to acetylcholine infused into the brachial artery in SCD patients with low levels of apo A-I (Blood 2009,113(5):1122-8). This finding has led to a translational clinical trial in our group directed at increasing apoA-I in SCD subjects who have low basal values. Subsequent analysis of proteomic screen data has been aimed at identifying the most significant additional candidate peaks to be further investigated as potential plasma biomarkers of PH and SCD. Confirmation of hypothesized identities and validation as biomarkers are planned by well-established immunoassay.

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