A subset of patients with systemic lupus erythematosus fails to degrade DNA from multiple clinically relevant sources

Arthritis Research & Therapy - Tập 17 - Trang 1-10 - 2015
Jonatan Leffler1,2, Katarzyna Ciacma1, Birgitta Gullstrand3, Anders A. Bengtsson3, Myriam Martin1, Anna M. Blom1
1Lund University, Department of Translational Medicine, Section of Medical Protein Chemistry, Malmö, Sweden
2Telethon Kids Institute, University of Western Australia, Subiaco, Australia
3Lund University, Department of Clinical Sciences, Section of Rheumatology, Skåne University Hospital Lund, Lund, Sweden

Tóm tắt

Patients with systemic lupus erythematosus (SLE) have a decreased ability to clear cell remnants and multiple deficiencies in the ability to degrade cellular chromatin have been linked to the disease. Since the discovery of neutrophil extracellular traps (NETs), a renewed interest has been sparked in this field of research with multiple studies reporting a decreased ability of patients with SLE to degrade NETs. In this study we extend these findings by investigating the ability of patients with SLE to degrade chromatin from multiple clinically relevant sources. We use flow cytometry in combination with NET degradation and DNA zymogram assays to investigate the ability of sera from SLE patients to degrade chromatin from three different sources of DNA such as NETs, apoptotic and necrotic cells. This ability was further associated with clinical manifestations. We found that 61 % of the patients had an affected degradation of at least one chromatin source. Further, degradation of NETs correlated with degradation of chromatin from secondary necrotic cells but not with degradation of chromatin from primary necrotic cells. Patients who fail to degrade several forms of DNA more often display anti-nuclear and nephritic involvement whereas this is not observed in patients with decreased ability to degrade chromatin from primary necrotic cells. The majority of patients with SLE has a decreased ability to degrade chromatin from clinically relevant sources. This decreased ability is further reflected in their clinical presentation.

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