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

• Published in: Blood Vol. 126; no. 24; pp. 2601 - 2610
• Main Authors: Hofer, Thomas P., Zawada, Adam M., Frankenberger, Marion, Skokann, Kerstin, Satzl, Anna A., Gesierich, Wolfgang, Schuberth, Madeleine, Levin, Johannes, Danek, Adrian, Rotter, Björn, Heine, Gunnar H., Ziegler-Heitbrock, Loems
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.12.2015
• Subjects: Amino Sugars - analysis; Antigens, CD1 - analysis; Dendritic Cells - chemistry; Female; Flow Cytometry; Gene Expression Profiling; Genes, MHC Class II; Genome-Wide Association Study; Glycoproteins - analysis; GPI-Linked Proteins - analysis; HLA-D Antigens - analysis; Humans; Immunomagnetic Separation; Leukoencephalopathies - genetics; Leukoencephalopathies - immunology; Leukoencephalopathies - pathology; Lipopolysaccharide Receptors - analysis; Male; Middle Aged; Monocytes - chemistry; Monocytes - classification; Monocytes - immunology; Point Mutation; Receptor, Macrophage Colony-Stimulating Factor - genetics; Receptors, IgG - analysis; Reverse Transcriptase Polymerase Chain Reaction; Sarcoidosis - immunology; Sarcoidosis - pathology; Young Adult
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2015-06-651331

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. •The slan marker can be used to define nonclassical and intermediate monocytes in human blood.•slan-negative intermediate monocytes are expanded in sarcoidosis, and slan-positive nonclassical monocytes are depleted in HDLS.