Premium
Proteomic discovery in sickle cell disease: Elevated neurogranin levels in children with sickle cell disease
Author(s) -
Lance Eboni I.,
Faulcon Lisa M.,
Fu Zongming,
Yang Jun,
WhyteStewart Donna,
Strouse John J.,
BarronCasella Emily,
Jones Kimberly,
Van Eyk Jennifer E.,
Casella James F.,
Everett Allen D.
Publication year - 2021
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.202100003
Subject(s) - medicine , proteome , haptoglobin , neurogranin , biomarker , disease , sickle cell anemia , cell , hemopexin , gastroenterology , bioinformatics , biology , biochemistry , enzyme , heme , protein kinase c
Purpose Sickle cell disease (SCD) is an inherited hemoglobinopathy that causes stroke and silent cerebral infarct (SCI). Our aim was to identify markers of brain injury in SCD. Experimental Design 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‐Center Clinical Trial (SIT Trial) to age‐matched, healthy non‐SCD controls. Results From the SCD group, 1172 proteins were identified. Twenty‐five percent (289/1172) were solely in the SCI group. Twenty‐five proteins with enriched expression in the human brain were identified in the SCD group. Neurogranin (NRGN) was the most abundant brain‐enriched 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 ng/mL, N = 100) compared to control participants (0.12 ng/mL, N = 25, p < 0.0004). Conclusions and Clinical Relevance NRGN levels are elevated in children with SCD. NRGN and other brain‐enriched plasma proteins identified in plasma of children with SCD may provide biochemical evidence of neurological injury.