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Blood Biomarkers of Pulmonary Hypertension in Sickle Cell Disease: A Cross-Sectional Proof-of-Concept Study

Babu, Varshini (2022) Blood Biomarkers of Pulmonary Hypertension in Sickle Cell Disease: A Cross-Sectional Proof-of-Concept Study. Master Essay, University of Pittsburgh.

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Background. Sickle cell disease (SCD) is an inherited blood disorder that is associated with hemolysis, inflammation, and coagulopathy. Pulmonary hypertension (PH) is a comorbidity of SCD that impacts many adult patients. These patients have a much higher mortality risk when compared to their counterparts without PH. There is little knowledge on the proteomic profile of PH in SCD. Our aim was to conduct a proof-of-concept study to explore targeted serum protein biomarkers that are differentially expressed in SCD patients with elevated tricuspid regurgitation velocities (TRV) to explore their corresponding pathways.
Methods. We used data from the Walk-PHaSST study for this investigation. One group of patients had a TRV ≤ 2.6 m/sec (n=35) and another had TRV ≥ 2.9 m/sec (n=35). The serum concentrations of 92 protein biomarkers were measured using an OLINK cardiovascular panel. The Hochberg method was used to calculate the false discovery rate. A volcano plot was created using the Bonferroni correction. We tested the correlation of the differentially expressed biomarkers with clinical variables measured in blood samples of the participants.
Results. Six proteins passed a Bonferroni corrected overall critical p-value < 0.00054. This includes T-cell surface glycoprotein (CD4), lymphotactin (XCL1), SLAM family member 7 (SLAMF7), galectin-9 (GAL9), TNF-related apoptosis-inducing ligand receptor 2 (TRAILR2), and tumor necrosis factor receptor superfamily member 11A (TNFRSF11A). CD4, XCL1, GAL9, and TNFRSF11A are involved in T-cell regulation, and immunological and inflammatory functioning. TRAILR2 is involved in apoptosis activation. All six biomarkers are involved in endothelial dysfunction. Among these biomarkers, CD4, GAL9, TRAILR2, and TNFRSF11A, were slightly positively correlated with white blood cell (r > 0.20). A significantly negative correlation was observed between neutrophil count and TNFRSF11A, GAL9, XCL1, SLAMF7, and CD4 (r < -0.21). We observed a strong, positive correlation between all proteins and serum NT-proBNP levels (r > 0.44).
Conclusion. Circulatory protein markers of immune response, apoptosis, and endothelial function are highly expressed in SCD patients with elevated TRV. This provides evidence of the public health significance of these protein biomarkers, as they have potential to be utilized as diagnostic, predictive, prognostic, or therapeutic markers for PH in patients with SCD.


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Item Type: Other Thesis, Dissertation, or Long Paper (Master Essay)
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Babu, Varshinivab57@pitt.eduVAB57
ContributionContributors NameEmailPitt UsernameORCID
Committee ChairGlynn, Nancy W.epidnwg@pitt.eduepidnwgUNSPECIFIED
Committee MemberNouraie, Seyed Mehdisnouraie@pitt.edusnouraieUNSPECIFIED
Committee MemberZhang, Yingzezhang3@pitt.eduzhang3UNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Vascular Medicine Institute
Date: 16 May 2022
Date Type: Completion
Number of Pages: 41
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Epidemiology
Degree: MPH - Master of Public Health
Thesis Type: Master Essay
Refereed: Yes
Date Deposited: 16 May 2022 13:20
Last Modified: 16 May 2022 13:20


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