Session Information
Date: Tuesday, November 7, 2017
Session Title: Systemic Lupus Erythematosus – Human Etiology and Pathogenesis Poster II
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: It is well established that up to 70% of systemic lupus erythematosus (SLE) patients will develop Lupus Nephritis (LN). Recent studies have revealed that infiltrating monocytes and macrophages are associated with LN pathogenesis. Studies by our group and others have studied the potential role of HO-1, a haem-degrading enzyme with anti-inflammatory properties, in the modulation of immune cells and SLE development. Therefore, we decided to explore the contribution of HO-1 expression to LN pathogenesis.
Methods: All patients were recruited at Hospital Clínico of Pontificia Universidad Católica de Chile, fulfilled the ACR SLE classification criteria and had proliferative LN confirmed by renal biopsy (Class III, IV or V ISN/RPS). All individuals signed an informed consent form. Monocytes were purified using pan-monocytes MACS kit from peripheral blood mononuclear cells (PBMCs) of LN patients and healthy controls (HC). The CD16+ inflammatory monocytes were quantified. FACS was used to measure phagocytosis, HO-1 expression and ROS levels. The latter were determined using a CellRox Kit.
Results: We found that monocytes purified from LN patients show significant differences as compared to healthy controls (HC) in all parameters analyzed. LN patients have increased the CD16+ inflammatory monocytes (LN: 6.72±0.98%, HC: 4.07±0.48%; p<0.05). HO-1 protein expression is decreased in monocytes from LN patients compared with HC (LN: 1572±481, HC: 4789±911; p=0.005). ROS levels are elevated in LN monocytes showing similar values to monocytes from HC treated with a ROS inducer (HC: 3509±584, HC+TBHP: 8436±1909, LN: 8355±1714). Furthermore, the phagocytic activity is increased in LN monocytes (77.97±3.31%) compared to HC (39.63±2.75%). Moreover, our preliminary data indicate that HO-1 induction leads to down regulation of ROS production in LN (~60%) and HC (~40%) leaving both in similar ROS production. In addition, phagocytic activity is also decreased in LN and HC monocytes in the presence of HO-1 inducer (~30%). Furthermore, in renal biopsies of LN patients we observed that HO-1 expression is increased in renal tubular epithelial cells compared to HC.
Conclusion: Decreased HO-1 expression in circulating monocytes of LN patients leads to higher ROS production and higher phagocytic activity, which contributes to renal injury. We propose that increased HO-1 levels in epithelial renal cells might be an attempt of the kidney to protect itself from damage. Since ROS levels and phagocytosis are reduced when a HO-1 inducer is used, we also speculate that HO-1 induction in monocytes might exert a cytoprotective role in LN by regulating innate immunity. FONDECYT N°1150173.
Acknowledgements: We would like to extend our appreciation to all the volunteers that participated in this study.
To cite this abstract in AMA style:
Cuitino L, Obreque J, Gajardo-Meneses P, Méndez GP, Kalergis AM, Llanos C. HO-1 Expression in Monocytes Might Regulate Kidney Damage in Lupus Nephritis Patients [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/ho-1-expression-in-monocytes-might-regulate-kidney-damage-in-lupus-nephritis-patients/. Accessed November 19, 2018.« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/ho-1-expression-in-monocytes-might-regulate-kidney-damage-in-lupus-nephritis-patients/