{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T03:00:24Z","timestamp":1778814024353,"version":"3.51.4"},"reference-count":14,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics Clinical Apps"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Pulmonary hypertension (PH) is a chronic complication of sickle cell disease (SCD) with limited known biomarkers, beyond increases in plasma brain natriuretic peptide levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Design<\/jats:title><jats:p>We conducted a proof\u2010of\u2010concept study to identify serum protein biomarkers that were differentially expressed in SCD patients with elevated tricuspid regurgitation velocity (TRV\u2014a noninvasive marker of PH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found 41 out of 92 target proteins that were significantly different between the nonelevated (TRV\u00a0\u2264\u00a02.6 m\/s; <jats:italic>N<\/jats:italic> = 35) and highly elevated TRV group (TRV\u00a0\u2265\u00a02.9 m\/s; <jats:italic>N<\/jats:italic> = 35, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05). Six of them passed a Bonferroni correction (<jats:italic>p<\/jats:italic> value &lt; 0.0005), including T\u2010cell surface glycoprotein, lymphotactin, SLAM family member 7, galectin\u20109, TNF\u2010related apoptosis\u2010inducing ligand receptor 2, and tumor necrosis factor receptor superfamily member 11A. We observed up to a 1.2\u2010fold increase in the high TRV group for these six proteins. These six proteins had a strong positive correlation with serum NT\u2010proBNP levels (a positive control marker elevated in PH [<jats:italic>r<\/jats:italic> \u2265 0.44]). Additionally, these markers correlated with other clinical parameters of PH in SCD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Circulatory protein markers of the immune response are increased in SCD patients with elevated TRV as compared to those without elevated TRV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Summary<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>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.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These biomarkers may be important tools for risk\u2010stratifying patients with SCD or targets for therapeutic intervention.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/prca.70019","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T07:24:33Z","timestamp":1754897073000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeted Proteomic Analysis of Sickle Cell Disease Patients With Elevated Tricuspid Regurgitation Velocity"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1391-2562","authenticated-orcid":false,"given":"Varshini","family":"Babu","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane A.","family":"Little","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Hematology and Oncology University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia R.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Emory University School of Medicine  Atlanta Georgia USA"},{"name":"Children's Healthcare of Atlanta  Atlanta Georgia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Machado","sequence":"additional","affiliation":[{"name":"Department of Medicine Indiana University  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Imperial College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory J.","family":"Kato","sequence":"additional","affiliation":[{"name":"Hematology Therapeutic Area CSL Behring  King of Prussia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor R.","family":"Gordeuk","sequence":"additional","affiliation":[{"name":"Sickle Cell Center Division of Hematology and Oncology Department of Medicine University of Illinois at Chicago  Carol Stream Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark T.","family":"Gladwin","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingze","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyed Mehdi","family":"Nouraie","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine University of Pittsburgh  Pittsburgh Pennsylvania 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