Cellular and Molecular mechanisms in Systemic Lupus Erythematosus

There are indeterminate molecular mechanisms underpinning disease activity in SLE. A CD163high, anti-inflammatory subpopulation of monocytes can be induced by in vitro culture with steroids or immuno-regulatory cytokines. Bacterial infection and IFN drive the opposite proimmune (HLA-DRhigh,) phenotype. It is likely that conflict exists in SLE between factors tending to promote HLA-DR (e.g. type I and II IFN) and CD163 (e.g. IL-10, steroids). Increase in CD163 expression has been coupled with increase intracellular HO-1 expression. Monocytes with this phenotype have anti-inflammatory and anti-oxidant properties. Induction of HO-1 by hemin injections has reportedly ameliorated lupus nephritis in animals. The phenotype described by HLA-DR and CD163 may reflect antigen presenting capacity and inflammatory status and may be related to disease severity in patients.

This study aims to investigate the influence of disease activity and oral corticosteroids on HLADR and CD163 expression respectively, in circulating monocytes in persons with SLE.

Methodology:

Consecutive participants with SLE visiting the Rheumatology Clinic of the Queen Elizabeth Hospital were enrolled in the study with informed signed consent. Basis demographics along with the current medication regime were collected and participants were stratified based on corticosteroid use. A thorough systematic examination, utilizing SLEDAI as a guide, was afforded to all participants. Based on the presence or absence of clinical signs associated with a lupus flare, participants are stratified as ‗active‘ or ‗quiescent‘. Blood samples are collected in EDTA and analysed by three-colour flow cytometry to determine the mean fluorescent intensity (MFI) of HLA-DR and CD163 on gated CD14+ve cells. Data was analysed by an unpaired t-test using Graph Pad Prism v 5.

Progress update/results:

This project has been ongoing less than one year and preliminary results demonstrate an increase of CD163 MFI in the corticosteroid (n=27) versus the non-corticosteroid group (n=13) [1.3±0.1 vs. 0.9±0.1 (p=0.01)].]. The effect of disease status on HLA-DR was insignificant.

Future plans:

In the future we intend to increase the panel of investigations to include cytokines and intracellular markers and relate these to clinical status by utilizing a disease activity index. This will allow a better understanding of the molecular physiology involved in SLE and could offer a possible target for future therapeutic regimes.