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 whilst more recently B Lymphocyte Stimulator (BLyS) has been demonstrated to play a key role in the pathogenesis of SLE. Despite the fact that monocytes are one of the key producers of BLyS, the effect of BLyS on monocyte activation in SLE patients has not been determined.
Objectives To characterise the activation state of SLE monocytes in their resting state and in response to BLyS.
Methods Activation of CD14+ monocytes was characterised in the resting state and following BLyS stimulation in both healthy controls and SLE patients by flow cytometry. Both antigen presenting capacity and co-stimulatory molecule expression were assessed using the following surface markers: CD80, CD86 and HLA-DR. Differences in activation states between groups were examined using the Mann Whitney whilst within group analysis was performed using the Wilcoxon signed-rank test. Spearman's correlation coefficient was also used to assess the relationship between HLA-DR expression and CD80/CD86.
Results 25 SLE Patients (as per ACR diagnostic criteria) were recruited. Basal expression of CD80 and HLA-DR was increased on patient monocytes compared to controls (CD80 6.35% v 1.5%, p=0.036, HLA-DR 61.65% v 47.30%, p=0.048). No relationship was observed between disease activity as per SLEDAI and resting SLE patient monocyte function.
Interestingly despite their baseline hyper-activated state, following stimulation with BLyS, SLE patients significantly upregulated CD80, CD86 and HLA-DR expression [(CD80 6.35% v 8.4%, p=0.007, CD86 80.8% v 84.6%, p=0.03, HLA-DR 61.65% v 74.95%, p=0.001). In contrast the healthy control volunteers failed to significantly upregulate any of the surface markers following BLyS stimulation indicating that SLE patients monocytes are more responsive to the effects of BLyS. In support of this SLE patients expressed more CD80 and HLA-DR following stimulation than controls (CD 80 8.4% v 2.5%, p=0.0031, HLA-DR 74.95% v 52.90%, p=0.018).
When the relationship between CD80/CD86 and HLA-DR surface expression was examined no significant correlation was observed between them in the resting state. However following BLyS stimulation a strong correlation was seen between both CD80/CD86 and HLA-DR expression in SLE patients (CD80 vs HLA-DR:Spearman r =0.64, p=0.005, CD86 vs HLA-DR: Spearman r =0.60, p=0.012)
Conclusions Our results suggest that SLE patient monocytes have a hyperactivated phenotype which consequentially results in an enhanced response to BLyS exposure compared to healthy control monocytes. As BLyS plays a significant role in monocyte function in SLE this finding warrants further investigation.
Disclosure of Interest None declared
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