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The proteome of neutrophils in sickle cell disease

ABSTRACT: Polymorphonuclear neutrophils are key actors in the pathophysiology of sickle cell disease, but specific factors underlying their activation and sustained inflammation are not well documented. In the present study, we investigated the proteome of neutrophils by a label-free global comparative approach between 4 non-treated sickle patients (SS genotype) at steady state and 4 healthy donors. We identified 101 proteins differentially expressed in SS and normal neutrophils. We found overexpression of CD64 and under-expression of CD62L suggestive of an activated and aged neutrophil profile in SS patients. Comparison of the two proteomes revealed a strong involvement of the type 1 interferon (IFN) response pathway with a 3- to 84-fold increase of type 1 IFN-induced proteins in SS neutrophils, and overexpression of STAT1 and STAT2. Thus, we next determined the plasmatic concentration of type 1 IFNs (IFNα and IFNβ) using the digital-ELISA technology and found a significant higher concentration of IFNα in the plasma from half of our SS patients compared to controls. Overall, a dramatic high-level expression of IFNα signaling proteins in neutrophils from SS patients suggests auto-inflammatory-like phenotype in sickle cell disease at steady state. This finding could open the way to new anti-inflammatory therapies.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Neutrophil, Blood

DISEASE(S): Sickle Cell Anemia

SUBMITTER: François GUILLONNEAU

LAB HEAD: Bérengère Koehl

PROVIDER: PXD014457 | Pride | 2020-11-11

REPOSITORIES: Pride

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			Action	DRS
	ClVK171109_Patient_SCX1_F23777.raw	Raw
	ClVK171109_Patient_SCX2_F23778.raw	Raw
	ClVK171109_Patient_SCX3_F23779.raw	Raw
	ClVK171109_Patient_SCX4_F23780.raw	Raw
	ClVK171109_Patient_SCX5_F23781.raw	Raw

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The proteome of neutrophils in sickle cell disease

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