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AB0029 Characterising monocyte responses to toll-like receptors in irish sle patients.
  1. E. M. McCarthy1,
  2. J. Ni Gabhann2,
  3. J. C. Byrne2,
  4. K. Stacey2,
  5. B. Coffey2,
  6. S. Smith2,
  7. R. Mahony2,
  8. C. de Chaumont2,
  9. A.-B. Mongey3,
  10. E. S. Molloy3,
  11. S. Donnelly4,
  12. D. Howard1,
  13. P. O’Connell1,
  14. G. Kearns1,
  15. C. A. Jefferies2
  1. 1Rheumatology Department, Beaumont Hospital
  2. 2Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland
  3. 3Rheumatology Department, St. Vincents University Hospital
  4. 4Rheumatology Department, Mater Misericordiae University Hospital, Dublin, Ireland

Abstract

Background Systemic Lupus Erythematosus(SLE) involves complex interactions between the innate and adaptive immune systems. Monocytes are increasingly recognised to play a key role in the dysregulated immune response seen in SLE, with members of the Toll like receptor(TLR) family, specifically TLR7 and TLR9, identified as key players.

Objectives To characterise the activation state of SLE monocytes in their resting state and following TLR stimulation.

Methods Activation of CD14+ monocytes was characterised in the resting state and following TLR stimulation by flow cytometry using the following markers: CD80, CD86, HLA-DR and HLA-ABC. Samples were stimulated with TLR 3,4,7 and 9. Serum cytokine levels were determined by multiplex technology. Disease Activity was recorded by SLEDAI. Differences in activation states were examined using the Mann Whitney. Spearmans correlation coefficient was used to assess the relationship between cytokine levels, disease activity and monocyte activation.

Results 25 SLE Patients were recruited. Resting state lupus patient monocytes have higher expression of surface CD86 compared to controls(85.32% v 64.42 %, p<0.018). Both inactive and active patients express significantly more CD86 in their resting state than controls. Whilst no significant difference in HLA-DR expression was seen between SLE patients and controls in the resting state, inactive SLE patients were observed to express more HLA-DR than active patients(29.67% v 13.96%, p=.03) with a significant inverse correlation being observed between disease activity and resting monocyte HLA-DR expression(r= -0.596, p=.014).

A significant relationship was observed between percentage CD80 cell surface expression and serum IFN-γ production(r=0.69, p=0.016) and percentage CD86 and TNF-α production(r=-0.615, p=0.037) in SLE patients. Monocyte HLA-DR levels also showed significant correlation with both serum IL-6(r=0.837, p=0.001) and IL-10(r= -0.623, p=0.03).

Regarding TLR ligands, a significant increase in monocyte CD80 expression from the resting state was observed in controls following stimulation with each of the TLR ligands. No significant increase in CD80 expression was observed in SLE patient monocytes for any of the TLR stimulations compared to their resting state, indicating SLE patients are less responsive to TLR stimulation.

In contrast, whilst SLE patient monocytes failed to upregulate HLA-DR expression following TLR3 stimulation in comparison to healthy control monocytes(Pt 25.7% v control 40.3%, p=0.047) the reverse effect was observed for TLR9 stimulation, with SLE monocytes upregulating HLA-DR expression whereas no increase was observed in healthy control monocytes in response to TLR9(Patient 36% v Control 21%, p=0.03).

Conclusions Our results suggest that SLE patient monocytes are hyperactivated in their resting state with a significant relationship seen between resting monocyte HLA-DR expression and disease activity. SLE patients monocytes appear less responsive to TLR stimulation than controls in part due to this baseline hyperactivated state.

Disclosure of Interest None Declared

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