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Abstract: PO0012

Plasticity of Neutrophil Subsets in ANCA Vasculitis and COVID-19

Session Information

Category: Coronavirus (COVID-19)

  • 000 Coronavirus (COVID-19)

Authors

  • Ui Mhaonaigh, Aisling C., Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland
  • Dwivedi, Amrita, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland
  • Little, Mark Alan, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland

Group or Team Name

  • Renal Inflammation Group
Background

A population of granulocytes appear in the PBMC layer of density separated blood and are termed Low Density Granulocytes (LDGs). These are seen in many conditions including cancer, sepsis, autoimmunity and pregnancy. We previously identified LDGs in acute and remission ANCA vasculitis (AAV) and hypothesise that these LDGs are also present in Covid-19 (C-19) and our aim is to phenotype these cells and determine whether LDGs are a disease specific cellular response to inflammation. Of particular interest is the expression of intracellular Arginase 1 (Arg-1), an enzyme linked to T cell suppression in many disease situations.

Methods

LDGs were isolated using a modified percoll preparation and analysed by both traditional and imaging flow cytometry, in patients with active and remission ANCA vasculitis, in patients with severe moderate and mild C-19 and in healthy controls. The phenotyping panel included CD14, CD15, CD16, CD10, CD33, CD62l. Intracellular Arg-1 was stained following permeabilisation with saponin.

Results

We identified extensive populations of LDGs in both AAV and Covid-19 peripheral blood. LDG levels are associated with disease severity. Arginase 1 is differentially expressed in neutrophil populations from AAV and C-19. In C-19 Arginase levels are correlated to disease severity suggesting that Arginase release may be associated with favourable outcome. Interestingly, all neutrophil fractions show lower levels of Arginase in C-19 patients whereas in AAV only LDGs have lower levels. Healthy controls have high Arginase expression.

Conclusion

Neutrophil subsets display disease specific responses in C-19 and AAV demonstrating their plasticity in inflammatory settings and warrant further investigation.

Funding

  • Government Support – Non-U.S.