Targeted proteomic analysis of sickle cell disease patients with elevated tricuspid regurgitation velocity

Purpose: Pulmonary hypertension (PH) is a chronic complications of sickle cell disease (SCD) with limited known biomarkers, beyond increases in plasma brain natriuretic peptide levels. Experimental Design: We conducted a proof-of-concept study to identify serum protein biomarkers that were differentially expressed in SCD patients with elevated tricuspid regurgitation velocity (TRV – a noninvasive marker of PH). Results: We found 41 out of 92 target proteins that were significantly different between the non-elevated (TRV≤2.6 m/sec; N = 35) and highly elevated TRV group (TRV≥2.9 m/sec; N = 35, p<0.05). Six of them passed a Bonferroni correction (p value < 0.0005) including T-cell surface glycoprotein, lymphotactin, SLAM family member 7, galectin-9, TNF-related apoptosis-inducing ligand receptor 2, and tumor necrosis factor receptor superfamily member 11A . We observed up to a 1.2-fold increase in the high TRV group for these six proteins. These six proteins had strong positive correlation with serum NT-proBNP levels (a positive control marker elevated in PH (r >= 0.44). Additionally, these markers correlated with other clinical parameters of PH in SCD. Conclusion: Circulatory protein markers of the immune response are increased in SCD patients with elevated TRV as compared to those without elevated TRV.