CD16 (FcRgammaIII) as a potential marker of osteoclast precursors in psoriatic arthritis.
BACKGROUND
Psoriatic arthritis (PsA) is a chronic inflammatory arthritis characterized by bone erosion mediated by osteoclasts (OC). Our previous studies showed an elevated frequency of OC precursors (OCP) in PsA patients. Here, we examined if OC arise from CD16-positive monocytes in PsA.


METHODS
Peripheral blood mononuclear cells (PBMC) or monocytes were isolated from human peripheral blood and sorted based on CD16 expression. Sorted cells were cultured alone or with bone wafers in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Enumeration and bone erosion activity of OC were examined after culture. The effects of tumor necrosis factor-alpha (TNFalpha), OC-promoting (M-CSF plus RANKL), and dendritic cell (DC)-promoting (GM-CSF plus interleukin (IL)-4) cytokines on CD16 surface expression were examined by flow cytometry.


RESULTS
PsA and psoriasis (Ps) subjects had a higher percentage of circulating inflammatory CD14+CD16+ cells than healthy controls (HC). Exposure of cells to OC-promoting, but not DC-promoting media, was associated with CD16 up-regulation. PBMC of Ps and PsA had a higher frequency of cells expressing intermediate levels of CD16. OC were mainly derived from CD16+ cells in PsA. Increased CD16 expression was associated with a higher bone erosion activity in PsA.


CONCLUSIONS
An increased frequency of circulating CD14+CD16+ cells was noted in PsA compared to controls, and intermediate levels of CD16 may suggest a transitional state of OCP during osteoclastogenesis. Intriguingly, TNFalpha blocked CD16 expression on a subset of CD14+ monocytes. Collectively, our data suggest that CD16 has the potential to serve as an OCP marker in inflammatory arthritis.
Chiu
Yahui Grace
YG
Allergy/Immunology & Rheumatology Unit, University of Rochester Medical School, 601 Elmwood Avenue, Rochester, NY 14642, USA. grace_chiu@urmc.rochester.edu
Shao
Tianmeng
T
Feng
Changyong
C
Mensah
Kofi A
KA
Thullen
Michael
M
Schwarz
Edward M
EM
Ritchlin
Christopher T
CT
D015535:Arthritis, Psoriatic / Q000378:metabolism* / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D019070:Cell Lineage; D002469:Cell Separation; D016207:Cytokines; D005434:Flow Cytometry; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D017452:Receptors, IgG