Email updates

Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.

Open Access Research article

Low production of reactive oxygen species in granulocytes is associated with organ damage in systemic lupus erythematosus

Anders A Bengtsson1, Åsa Pettersson2, Stina Wichert3, Birgitta Gullstrand4, Markus Hansson3, Thomas Hellmark2 and Åsa CM Johansson35*

Author Affiliations

1 Department of Clinical Sciences, Section of Rheumatology, Lund University and Skåne University Hospital, 221 85 Lund, Sweden

2 Department of Nephrology, Clinical Sciences in Lund, Lund University, BMC B13, 221 84 Lund, Sweden

3 Department of Haematology, Lund University, BMC B13, 221 84 Lund, Sweden

4 Department of Laboratory Medicine Lund. Section of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden

5 Clinical Immunology and Transfusion Medicine, University and Regional Laboratories Region Skåne, 221 85 Lund, Sweden

For all author emails, please log on.

Arthritis Research & Therapy 2014, 16:R120  doi:10.1186/ar4575

Published: 5 June 2014

Abstract

Introduction

Polymorphonuclear leukocytes (PMN) are main effector cells in the acute immune response. While the specific role of PMN in systemic lupus erythematosus (SLE) and autoimmunity is still unclear, their importance in chronic inflammation is gaining more attention. Here we investigate aspects of function, bone marrow release and activation of PMN in patients with SLE.

Methods

The following PMN functions and subsets were evaluated using flow cytometry; (a) production of reactive oxygen species (ROS) after ex vivo stimulation with phorbol 12-myristate 13-acetate (PMA) or Escherichia coli (E. coli); (b) capacity to phagocytose antibody-coated necrotic cell material; (c) PMN recently released from bone marrow, defined as percentage of CD10D16low in peripheral blood, and (d) PMN activation markers; CD11b, CD62L and C5aR.

Results

SLE patients (n = 92) showed lower ROS production compared with healthy controls (n = 38) after activation ex vivo. The ROS production was not associated with corticosteroid dose or other immunotherapies. PMA induced ROS production was significantly reduced in patients with severe disease. In contrast, neither ROS levels after E. coli activation, nor the capacity to phagocytose were associated with disease severity. This suggests that decreased ROS production after PMA activation is a sign of changed PMN behaviour rather than generally impaired functions. The CD10CD16low phenotype constitute 2% of PMN in peripheral blood of SLE patients compared with 6.4% in controls, indicating a decreased release of PMN from the bone marrow in SLE. A decreased expression of C5aR on PMN was observed in SLE patients, pointing towards in vivo activation.

Conclusions

Our results indicate that PMN from SLE patients have altered function, are partly activated and are released abnormally from bone marrow. The association between low ROS formation in PMN and disease severity is consistent with findings in other autoimmune diseases and might be considered as a risk factor.