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Kidney Week

Abstract: FR-PO364

The Expansion and Phenotype of HLA-DRhi Intermediate Monocytes in CKD

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Cormican, Sarah, National University of Ireland Galway, Galway, Ireland
  • Naicker, Serika D., National University of Ireland Galway, Galway, Ireland
  • Negi, Neema, National University of Ireland Galway, Galway, Ireland
  • Dennedy, Michael Conall, National University of Ireland Galway, Galway, Ireland
  • Griffin, Matthew D., National University of Ireland Galway, Galway, Ireland
Background

A chronic microinflammatory state occurs in CKD, one aspect of which is monocyte subset dysregulation. Monocytes are comprised of one major ("classical") and two minor ("intermediate" and "nonclassical") subsets. The intermediate monocyte (IM) subset is pro-inflammatory and numerically increased in CKD. Having recently reported that human IM may be further subdivided into HLA-DRmid and HLA-DRhi subpopulations and that IM increase in CKD is specific to the HLA-DRhi IM subpopulation, we aimed to determine whether HLA-DRhi IM display distinctive expression of surface proteins required for endothelial adhesion and transmigration in health and in CKD.

Methods

Adult outpatients with CKD or healthy controls (HC) provided blood samples by informed consent. Peripheral blood mononuclear cells (PBMC) were isolated and analyzed by multi-colour flow cytometry for monocyte subpopulation numbers and surface protein expression levels (CD45, CD14, CD16, HLA-DR, CCR2, CCR5, CCR7, CX3CR1, CD11a, CD11b, CD11c, CD62L, CD49d and CD162).

Results

Consistent with prior results, higher numbers of total IM (p=0.03) and in HLA-DRhi IM (p=0.015) were present in PBMC from CKD vs HC. IM had higher expression of CCR5 than classical and non-classical monocytes (p<0.0001). Among the IM, high CCR5 was specific to HLA-DRhi IM (p=0.002). Surface expression of the integrin chains CD11b and CD11c was also highest among HLA-DRhi IM (p<0.001). For CCR5, CD11b and CD11c, HLA-DRhi IM surface expression was similar for CKD and HV. In contrast, HLA-DRhi IM surface expression of CX3CR1 (the receptor for fractalkine/CX3CL1) was higher in CKD vs. HV (p=0.02). Finally, we also observed that surface expression of the selectin ligand PSGL-1/CD162 was higher on classical monocytes (p=0.008) and HLA-DRmid IM (p<0.001) in CKD compared to HC. Other surface proteins analyzed also showed distinctive patterns of expression among the monocytes subsets that were not modulated in CKD.

Conclusion

Among circulating monocyte subpopulations, several surface proteins which mediate endothelial adhesion and transmigration are highly expressed by HLA-DRhi IM, a distinctive subpopulation that is numerically increased in CKD. Functional analyses may help to determine whether CKD-associated expansion of HLA-DRhi IM contributes to microvascular inflammation and progressive fibrosis.

Funding

  • Private Foundation Support