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Our aim was to identify markers of brain injury in SCD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Design<\/jats:title><jats:p>Plasma proteomes were analyzed using a sequential separation approach of hemoglobin (Hb) and top abundant plasma protein depletion, followed by reverse phase separation of intact proteins, trypsin digestion, and tandem mass spectrometry. We compared plasma proteomes of children with SCD with and without SCI in the Silent Cerebral Infarct Multi\u2010Center Clinical Trial (SIT Trial) to age\u2010matched, healthy non\u2010SCD controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>From the SCD group, 1172 proteins were identified. Twenty\u2010five percent (289\/1172) were solely in the SCI group. Twenty\u2010five proteins with enriched expression in the human brain were identified in the SCD group. Neurogranin (NRGN) was the most abundant brain\u2010enriched protein in plasma of children with SCD. Using a NRGN sandwich immunoassay and SIT Trial samples, median NRGN levels were higher at study entry in children with SCD (0.28\u00a0ng\/mL, <jats:italic>N<\/jats:italic>\u00a0=\u00a0100) compared to control participants (0.12\u00a0ng\/mL, <jats:italic>N<\/jats:italic>\u00a0=\u00a025, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.0004).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p>NRGN levels are elevated in children with SCD. NRGN and other brain\u2010enriched plasma proteins identified in plasma of children with SCD may provide biochemical evidence of neurological injury.<\/jats:p><\/jats:sec>","DOI":"10.1002\/prca.202100003","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T19:39:26Z","timestamp":1619725166000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Proteomic discovery in sickle cell disease: Elevated neurogranin levels in children with sickle cell disease"],"prefix":"10.1002","volume":"15","author":[{"given":"Eboni I.","family":"Lance","sequence":"first","affiliation":[{"name":"Department of Neurodevelopmental Medicine Kennedy Krieger Institute  Baltimore Maryland USA"},{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa M.","family":"Faulcon","sequence":"additional","affiliation":[{"name":"Food and Drug Administration  Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongming","family":"Fu","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology Department of Pediatrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology Department of Pediatrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna","family":"Whyte\u2010Stewart","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology Department of Pediatrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J.","family":"Strouse","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology Department of Pediatrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Division of Hematology Department of Medicine Duke University School of Medicine  Durham North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Barron\u2010Casella","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology Department of Pediatrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology Department of Pediatrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer E.","family":"Van Eyk","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"The Smidt Heart Institute Cedars\u2010Sinai Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James F.","family":"Casella","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology Department of Pediatrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen D.","family":"Everett","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology Department of Pediatrics Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61029-X"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-09-618579"},{"key":"e_1_2_9_4_1","first-page":"965","article-title":"The spectrum of brain MR abnormalities in sickle\u2010cell disease: A report from the Cooperative Study of Sickle Cell Disease","volume":"17","author":"Moser F. 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