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AB0195 HEME oxygenase-1 expression is decreased in monocytes from patients with systemic lupus erythematosus
  1. C. Llanos1,2,
  2. J. Mackern1,3,
  3. A. Herrada1,3,
  4. L. Carreño1,3,
  5. R. Gomez1,3,
  6. I. Anegon4,
  7. S. Iacobelli1,2,
  8. A. Kalergis1,3
  1. 1Millenium Institute on Immunology and Immunotherapy
  2. 2Inmunologia Clinica Y Reumatologia
  3. 3Departamento de Genética Molecular y Microbiología, Pontificia Universidad Catolica De Chile, Santiago, Chile
  4. 4INSERM UMR 643, Nantes, France

Abstract

Background Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by alterations affecting both the innate and adaptive immune systems [1]. Monocytes and dendritic cells from SLE patients display a stimulatory phenotype that promotes the activation of self-reactive T cells [2]. Monocytes are pluripotent cells capable of engulfing pathogens, releasing inflammatory molecules and presenting antigens to naïve T cells. One of the key molecules that controls monocyte function is Heme oxigenase-1 (HO-1), which catalyzes the degradation of heme into biliverdin, carbon monoxide (CO) and Fe+2. CO possesses immunosuppressive and anti-inflammatory abilities [3].

Objectives Therefore, the goal of this work was to assess HO-1 expression in monocytes from SLE patients and healthy controls (HC).

Methods 43 non-selected SLE patients that fulfilled the ACR criteria for SLE and 30 HC were recruited. In addition, 5 kidney-transplanted patients undergoing similar immunosuppressive treatment were included. All patients signed an informed consent form before entering the study. PBMCs were separated using the standard Ficoll centrifugation method. CD14+ monocytes and CD4+ T cells were sorted by FACS and HO-1 expression was measured by RT-PCR. HO-1 protein expression was determined by FACS. T cell activation parameters after staphylococcal enterotoxin A (SEA 50nM) stimulation were determined by FACS (IL2; CD69; CD25).

Results HO-1 mRNA levels were significantly decreased in CD14+ monocytes from SLE patients compared to HC (P<0.0075, Unpaired t test). When HO-1 protein expression in monocytes was assessed, similar results were observed (HO-1 relative expression (Geo mean SLE patient/Geo mean HC]; 0.73±0.05, P<0.0001 (Unpaired t test)). No differences in HO-1 mRNA levels or protein expression were observed between CD4+ T cells from SLE patients and HC. No differences between transplanted and lupus patients were found when HO-1 monocyte transcripts were evaluated in monocytes and CD4+ T cells. To assess the immunogenic capacity of monocytes, T cell activation assays in response to SEA stimulation were performed. No significant differences in T cell activation parameters, such as IL-2 production and CD69 expression were observed between lupus patients and HC.

Conclusions We found a significant decrease in HO-1 expression in monocytes from SLE patients, suggesting that an imbalance in HO-1 could play a role in SLE pathogenesis. The results obtained in kidney-transplanted patients suggest that this observation is not due to the immunosuppressive treatment. Since the results observed in SEA activation assays could be explained by defects in T cells from SLE patients, additional experiments to further evaluate the role of HO-1 in monocytes function are warranted.

  1. Llanos, C., et al. Curr Gene Ther 2011; 11(6).

  2. Steinbach, F., et al. Ann Rheum Dis 2000; 59(4): p. 283-8.

  3. Remy, S., et al., J immunol 2009; 182(4): p. 1877-84.

Disclosure of Interest None Declared

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