Varshini Babu, Jane A. Little, Claudia R. Morris, Roberto Machado, Simon Gibbs, Gregory A. Kato, Victor R. Gordeuk, MArk T. Gladwin, Yingze Zhang, Seyed Mehdi Nouraie
University of Pittsburgh. University of North Carolina at Chapel Hill. Emory University School of Medicine and Children’s Healthcare of Atlanta. Indiana University. Imperial College London. CSL Behring. University of Illinois at Chicago. University of Maryland School of Medicine.
United States and United Kingdom
Proteomics Clinical Applications
Proteomics Clin Appl 2025;
DOI: 10.1002/prca.70019
Abstract
Purpose: Pulmonary hypertension (PH) is a chronic complication 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 nonelevated (TRV ≤ 2.6 m/s; N = 35) and highly elevated TRV group (TRV ≥ 2.9 m/s; 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 a 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.
Summary: This study demonstrates that the circulatory protein markers of the immune response are increased in SCD patients with elevated TRV compared to those without elevated TRV. These biomarkers may be important tools for risk-stratifying patients with SCD or targets for therapeutic intervention.
Category
Class V. Pulmonary Hypertension Associated with Hematological, Systemic, Metabolic, Nutritional and Other Disorders
Diagnostic Testing for Pulmonary Vascular Disease. Non-invasive Testing
Potential Biomarkers Associated with Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease or Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: No