期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 97, 期 1, 页码 181-189出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.5A0614-311R
关键词
OLFM4; neutrophil subsets; antineutrophil cytoplasmic antibodies; NETs; neutrophil extracellular traps; phagocyte
资金
- Swedish Heart-Lung Foundation [20130442]
- King Gustaf V Memorial Foundation
- Ingabritt and Arne Lundbergs Research Foundation
- Clas Groschinsky Foundation
- Swedish Association Against Rheumatism
- Swedish state under the Agreement for Medical Training and Research (ALF)
Testing for the presence of ANCAs in circulation is part of the clinical examinations routinely performed upon suspected autoimmune disorders, mainly vasculitis. The auto-antibodies are typically directed toward neutrophil MPO or PR3. These are major granule-localized proteins, and similar to all hitherto-described ANCA antigens, they are expressed by all neutrophils, and ANCA-containing sera thus give rise to uniform reactivity toward all neutrophils in a sample. In this paper, we describe sera from 2 unrelated patients with diffuse inflammatory symptoms that gave rise to peculiar c-ANCA patterns, only reacting with a subpopulation (roughly 30%) of human neutrophils. By immuno-blotting, both sera reacted to the same antigen, which was expressed in intracellular granules. The antigen could be released to the extracellular milieu through secretion but also through the formation of NETs. Neutrophils have long been considered a homogenous cell population, but it is becoming increasingly clear that distinct subpopulations, defined by the presence or absence of certain proteins, exist. One such marker that defines a neutrophil subset is the granule protein OLFM4. The unusual, subset-restricted c-ANCA sera reacted only with OLFM4-positive neutrophils, and MS analysis revealed that the autoantigen was, in fact, OLFM4. These data describe for the first time a c-ANCA pattern reactive to only a subpopulation of neutrophils and identify the granule protein OLFM4 as a novel autoantigen.
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