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Blood. 2015 Dec 10;126(24):2601-10. doi: 10.1182/blood-2015-06-651331. Epub 2015 Oct 6.

slan-defined subsets of CD16-positive monocytes: impact of granulomatous inflammation and M-CSF receptor mutation.

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The EvA Study Center, Comprehensive Pneumology Center, Helmholtz-Zentrum München, Gauting, Germany;
Department of Internal Medicine IV, Nephrology and Hypertension, Saarland University Medical Center, Homburg, Germany;
Asklepios Fachklinik München-Gauting, German Center for Lung Research, Gauting, Germany;
Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität, München, Germany; and.
GenXPro, Frankfurt, Germany.


Human monocytes are subdivided into classical, intermediate, and nonclassical subsets, but there is no unequivocal strategy to dissect the latter 2 cell types. We show herein that the cell surface marker 6-sulfo LacNAc (slan) can define slan-positive CD14(+)CD16(++) nonclassical monocytes and slan-negative CD14(++)CD16(+) intermediate monocytes. Gene expression profiling confirms that slan-negative intermediate monocytes show highest expression levels of major histocompatibility complex class II genes, whereas a differential ubiquitin signature is a novel feature of the slan approach. In unsupervised hierarchical clustering, the slan-positive nonclassical monocytes cluster with monocytes and are clearly distinct from CD1c(+) dendritic cells. In clinical studies, we show a selective increase of the slan-negative intermediate monocytes to >100 cells per microliter in patients with sarcoidosis and a fivefold depletion of the slan-positive monocytes in patients with hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS), which is caused by macrophage colony-stimulating factor (M-CSF) receptor mutations. These data demonstrate that the slan-based definition of CD16-positive monocyte subsets is informative in molecular studies and in clinical settings.

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