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The effects of hydroxycarbamide on the plasma proteome of children with sickle cell anaemia

The effects of hydroxycarbamide on the plasma proteome of children with sickle cell anaemia
The effects of hydroxycarbamide on the plasma proteome of children with sickle cell anaemia
We have investigated changes in the plasma proteome of children with sickle cell anaemia (SCA) associated with hydroxycarbamide (HC) use, to further characterize the actions of HC. 51 children with SCA consented to take part in this study. 18 were taking HC at a median dose of 22mg/kg, and 33 were not on HC. Plasma was analyzed using an unbiased proteomic approach and a panel of 92 neurological biomarkers. HC was associated with increased haemoglobin (Hb) (89.8g/l vs 81.4g/l, P=0.007) and HbF (15.3 vs 6.7%, P<0.001). 17 proteins were decreased on HC compared to controls by a factor of <0.77, and six proteins showed >1.3 fold increased concentration. HC use was associated with reduced haemolysis (lower  globin chains, haptoglobin related protein, complement C9; higher hemopexin), reduced inflammation (lower -1-acid glycoprotein, CD5 antigen-like protein, ceruloplasmin, factor XII, immunoglobulins, cysteine-rich secretory protein 3, vitamin D-binding protein) and decreased activation of coagulation (lower factor XII, carboxypeptidase B2, platelet basic protein). There was a significant correlation between the increase in HbF% on HC and hemopexin levels (R=0.603, P=0.023). This study demonstrated three ways in which HC may be beneficial in SCA, and identified novel proteins, which may be useful to monitor therapeutic response.
0007-1048
Brewin, John
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Tewari, Sanjay
c68dfb2e-e24a-40be-b199-c110a430bf21
Menzel, Stephan
59552d21-d54a-4444-a62e-241e2aa8bde7
Kirkham, Fenella
1dfbc0d5-aebe-4439-9fb2-dac6503bcd58
Inusa, Baba
416c226a-c2e8-4e1f-bb76-f5e4f78a3380
Renney, George
dbd0f1d1-96a2-4c78-9a00-38227a0bdf17
Rees, David C
c072e170-7b48-4416-bf2d-79540f823242
Brewin, John
8445ebf9-e8eb-4fd3-9512-f15d146f1593
Tewari, Sanjay
c68dfb2e-e24a-40be-b199-c110a430bf21
Menzel, Stephan
59552d21-d54a-4444-a62e-241e2aa8bde7
Kirkham, Fenella
1dfbc0d5-aebe-4439-9fb2-dac6503bcd58
Inusa, Baba
416c226a-c2e8-4e1f-bb76-f5e4f78a3380
Renney, George
dbd0f1d1-96a2-4c78-9a00-38227a0bdf17
Rees, David C
c072e170-7b48-4416-bf2d-79540f823242

Brewin, John, Tewari, Sanjay, Menzel, Stephan, Kirkham, Fenella, Inusa, Baba, Renney, George and Rees, David C (2019) The effects of hydroxycarbamide on the plasma proteome of children with sickle cell anaemia. British Journal of Haematology. (In Press)

Record type: Article

Abstract

We have investigated changes in the plasma proteome of children with sickle cell anaemia (SCA) associated with hydroxycarbamide (HC) use, to further characterize the actions of HC. 51 children with SCA consented to take part in this study. 18 were taking HC at a median dose of 22mg/kg, and 33 were not on HC. Plasma was analyzed using an unbiased proteomic approach and a panel of 92 neurological biomarkers. HC was associated with increased haemoglobin (Hb) (89.8g/l vs 81.4g/l, P=0.007) and HbF (15.3 vs 6.7%, P<0.001). 17 proteins were decreased on HC compared to controls by a factor of <0.77, and six proteins showed >1.3 fold increased concentration. HC use was associated with reduced haemolysis (lower  globin chains, haptoglobin related protein, complement C9; higher hemopexin), reduced inflammation (lower -1-acid glycoprotein, CD5 antigen-like protein, ceruloplasmin, factor XII, immunoglobulins, cysteine-rich secretory protein 3, vitamin D-binding protein) and decreased activation of coagulation (lower factor XII, carboxypeptidase B2, platelet basic protein). There was a significant correlation between the increase in HbF% on HC and hemopexin levels (R=0.603, P=0.023). This study demonstrated three ways in which HC may be beneficial in SCA, and identified novel proteins, which may be useful to monitor therapeutic response.

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Proteomic HU BJH final - Accepted Manuscript
Restricted to Repository staff only until 10 May 2020.
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Accepted/In Press date: 10 May 2019

Identifiers

Local EPrints ID: 430254
URI: https://eprints.soton.ac.uk/id/eprint/430254
ISSN: 0007-1048
PURE UUID: 3cc4d223-cef9-4c29-a0e6-d9070241ba4e

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Date deposited: 23 Apr 2019 16:30
Last modified: 23 Apr 2019 16:30

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Contributors

Author: John Brewin
Author: Sanjay Tewari
Author: Stephan Menzel
Author: Fenella Kirkham
Author: Baba Inusa
Author: George Renney
Author: David C Rees

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