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. 2020 Dec 1;105(12):2851-2854.
doi: 10.3324/haematol.2019.238295.

The proteome of neutrophils in sickle cell disease reveals an unexpected activation of interferon alpha signaling pathway

Patricia Hermand  1 , Slim Azouzi  2 , Emilie-Fleur Gautier  3 , François Guillonneau  3 , Vincent Bondet  4 , Darragh Duffy  4 , Sebastien Dechavanne  1 , Pierre-Louis Tharaux  5 , Patrick Mayeux  3 , Caroline Le Van Kim  1 , Berengere Koehl  6
Affiliations

The proteome of neutrophils in sickle cell disease reveals an unexpected activation of interferon alpha signaling pathway

Patricia Hermand et al. Haematologica. .
No abstract available

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Figures

Figure 1.
Figure 1.
Proteomic analysis of neutrophils from healthy donors (AA) and SS genotype patients (SS) at steady state. (A) Overall proteomics results: number of proteins identified and quantified in at least one sample (A) or in at least three samples and in at least one group (B). (B) 2D enrichment analysis of the proteins expressed in at least 75% of the samples and in at least one group. Protein annotation databases from GOBP. Annotations out of the diagonal corresponding to differential expression in SS or AA samples are indicated. (C) Cluster analysis of proteins differentially expressed in SS and AA neutrophils. Proteins with significantly different expression values (P<0.05 and fold change>0.3) were selected, their LFQ values were z score transformed and analyzed by Euclidian clustering. Clusters 1 and 2 correspond to proteins upregulated and downregulated in SS neutrophils, respectively. (D) Cluster analysis of differentially expressed proteins with the “cellular response to type I interferon” GOBP annotation. (E) Characterization of neutrophils from SS patients by flow cytometry analysis, typical result: over-expression of the Fc fragment of IgG/CD64 and under-expression of L-selectin/CD62L. Data are presented as mean ± standard devaition (SD). Mann-Whitney test was used to compare SS and AA; *P<0.05 compared with AA; **P<0.01 compared with AA.
Figure 2.
Figure 2.
Activation of IFN-1 pathway in SS gentype neutrophils. (A) Representative images of Western blots for MX1, IFIT-1, ISG15, STAT 1, Phospho-STAT 1, STAT 2 and Phospho-STAT 2 expressed in neutrophils from healthy volunteers (AA, n=10) and SS patients (SS, n=10). The Western blots are represented as the ratio of the density of the specific band on the total protein in each sample. (B) Level of IFNα and IFNb in plasma from healthy donors (AA, n=34) and SS patients at basal state (SS, n=37) using a digital-ELISA assay (SIMOA). (C) Level of neutrophil elastase and nucleosome in plasma from healthy donors (AA, n=12) and SS patients at basal state (SS, n=28) using ELISA assay. Data are presented as mean ± standard devaitaion (SD). Mann-Whitney test was used to compare SS and AA; *P<0.05 compared with AA; **P<0.01 compared with AA; ***P<0.001.
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References

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