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Proteomic discovery in sickle cell disease: Elevated neurogranin levels in children with sickle cell disease
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 abun...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666096/ https://www.ncbi.nlm.nih.gov/pubmed/33915030 http://dx.doi.org/10.1002/prca.202100003 |
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author | Lance, Eboni I. Faulcon, Lisa M. Fu, Zongming Yang, Jun Whyte-Stewart, Donna Strouse, John J. Barron-Casella, Emily Jones, Kimberly Van Eyk, Jennifer E. Casella, James F. Everett, Allen D. |
author_facet | Lance, Eboni I. Faulcon, Lisa M. Fu, Zongming Yang, Jun Whyte-Stewart, Donna Strouse, John J. Barron-Casella, Emily Jones, Kimberly Van Eyk, Jennifer E. Casella, James F. Everett, Allen D. |
author_sort | Lance, Eboni I. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8666096 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-86660962022-09-01 Proteomic discovery in sickle cell disease: Elevated neurogranin levels in children with sickle cell disease Lance, Eboni I. Faulcon, Lisa M. Fu, Zongming Yang, Jun Whyte-Stewart, Donna Strouse, John J. Barron-Casella, Emily Jones, Kimberly Van Eyk, Jennifer E. Casella, James F. Everett, Allen D. Proteomics Clin Appl Article 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. 2021-05-24 2021-09 /pmc/articles/PMC8666096/ /pubmed/33915030 http://dx.doi.org/10.1002/prca.202100003 Text en https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Article Lance, Eboni I. Faulcon, Lisa M. Fu, Zongming Yang, Jun Whyte-Stewart, Donna Strouse, John J. Barron-Casella, Emily Jones, Kimberly Van Eyk, Jennifer E. Casella, James F. Everett, Allen D. Proteomic discovery in sickle cell disease: Elevated neurogranin levels in children with sickle cell disease |
title | Proteomic discovery in sickle cell disease: Elevated neurogranin levels in children with sickle cell disease |
title_full | Proteomic discovery in sickle cell disease: Elevated neurogranin levels in children with sickle cell disease |
title_fullStr | Proteomic discovery in sickle cell disease: Elevated neurogranin levels in children with sickle cell disease |
title_full_unstemmed | Proteomic discovery in sickle cell disease: Elevated neurogranin levels in children with sickle cell disease |
title_short | Proteomic discovery in sickle cell disease: Elevated neurogranin levels in children with sickle cell disease |
title_sort | proteomic discovery in sickle cell disease: elevated neurogranin levels in children with sickle cell disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666096/ https://www.ncbi.nlm.nih.gov/pubmed/33915030 http://dx.doi.org/10.1002/prca.202100003 |
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