Low Density Granulocytes in ANCA Vasculitis Are Heterogenous and Hypo-Responsive to Anti-Myeloperoxidase Antibodies
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2019Access:
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Ui Mhaonaigh, A. and Coughlan, A.M. and Dwivedi, A. and Hartnett, J. and Cabral, J. and Moran, B. and Brennan, K. and Doyle, S.L. and Hughes, K. and Lucey, R. and Floudas, A. and Fearon, U. and McGrath, S. and Cormican, S. and De Bhailis, A. and Molloy, E.J. and Brady, G. and Little, M.A., Low Density Granulocytes in ANCA Vasculitis Are Heterogenous and Hypo-Responsive to Anti-Myeloperoxidase Antibodies, Frontiers in Immunology, 10, 2603, 2019Download Item:
Abstract:
Low Density Granulocytes (LDGs), which appear in the peripheral blood mononuclear cell layer of density-separated blood, are seen in cancer, sepsis, autoimmunity, and pregnancy. Their significance in ANCA vasculitis (AAV) is little understood. As these cells bear the autoantigens associated with this condition and have been found to undergo spontaneous NETosis in other diseases, we hypothesized that they were key drivers of vascular inflammation. We found that LDGs comprise a 3-fold higher fraction of total granulocytes in active vs. remission AAV and disease controls. They are heterogeneous, split between cells displaying mature (75%), and immature (25%) phenotypes. Surprisingly, LDGs (unlike normal density granulocytes) are hyporesponsive to anti-myeloperoxidase antibody stimulation, despite expressing myeloperoxidase on their surface. They are characterized by reduced CD16, CD88, and CD10 expression, higher LOX-1 expression and immature nuclear morphology. Reduced CD16 expression is like that observed in the LDG population in umbilical cord blood and in granulocytes of humanized mice treated with G-CSF. LDGs in AAV are thus a mixed population of mature and immature neutrophils.
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https://www.frontiersin.org/articles/10.3389/fimmu.2019.02603/fullhttp://hdl.handle.net/2262/91156
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Science Foundation Ireland (SFI)
11/Y/B2093
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http://people.tcd.ie/doyles8http://people.tcd.ie/moranba
http://people.tcd.ie/mlittle
http://people.tcd.ie/fearonu
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https://www.frontiersin.org/articles/10.3389/fimmu.2019.02603/fullhttp://hdl.handle.net/2262/91156
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Frontiers in Immunology10
2603
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Immunology, Inflammation & Infection , RheumatologyDOI:
http://dx.doi.org/10.3389/fimmu.2019.02603Metadata
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