Tewari, S;
Renney, G;
Brewin, J;
Gardner, K;
Kirkham, F;
Inusa, B;
Barrett, JE;
... Reese, DC; + view all
(2018)
Proteomic analysis of plasma from children with sickle cell anemia and silent cerebral infarction.
Haematologica
, 103
(7)
pp. 1136-1142.
10.3324/haematol.2018.187815.
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Abstract
Silent cerebral infarction is the most common neurological abnormality in children with sickle cell anemia, affecting 30-40% of 14 year olds. There are no known biomarkers to identify children with silent cerebral infarcts, and the pathological basis is also unknown. We used an unbiased proteomic discovery approach to identify plasma proteins differing in concentration between children with and without silent cerebral infarcts. Clinical parameters and plasma samples were analysed from 51 children (mean age 11.8 years, range 6-18) with sickle cell anemia (HbSS). A total of 19 children had silent cerebral infarcts and 32 normal MRI; the children with silent infarcts had lower HbF levels (8.6 vs. 16.1%, P=0.049) and higher systolic blood pressures (115 vs. 108.6, P=0.027). Plasma proteomic analysis showed 13 proteins increased more than 1.3 fold in the SCI patients, including proteins involved in hypercoagulability (α2-antiplasmin, fibrinogen−γ chain, thrombospondin-4), inflammation (α2-macroglobulin, complement C1s and C3), and atherosclerosis (apolipoprotein B-100). Higher levels of gelsolin and retinol-binding protein 4 were also found in the population with silent infarcts, both of which have been linked to stroke. We investigated the genetic basis of these differences by studying 359 adults with sickle cell disease (199 with silent cerebral infarcts, 160 normal MRIs), who had previously undergone a genome-wide genotyping array. None of the genes coding for the differentially expressed proteins were significantly associated with silent infarction. Our study suggests that silent cerebral infarcts in sickle cell anemia may be associated with higher systolic blood pressure, lower HbF levels, hypercoagulability, inflammation and atherosclerotic lipoproteins.
| Type: | Article |
|---|---|
| Title: | Proteomic analysis of plasma from children with sickle cell anemia and silent cerebral infarction |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3324/haematol.2018.187815 |
| Publisher version: | https://doi.org/10.3324/haematol.2018.187815 |
| Language: | English |
| Additional information: | https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Hematology, RISK-FACTOR ANALYSIS, ISCHEMIC-STROKE, DISEASE, TRIAL, COMPLICATIONS, BIOMARKERS, SUBPHENOTYPES, HYPERTENSION, TRANSFUSIONS, PROTEINS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10069218 |
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