IMR Press / FBL / Volume 27 / Issue 12 / DOI: 10.31083/j.fbl2712333
Open Access Original Research
The Role of Plasma Cell-Free Mitochondrial DNA and Nuclear DNA in Systemic Lupus Erythematosus
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1 Division of Allergy, Immunology & Rheumatology, Department of Internal Medicine, Mackay Memorial Hospital, 104 Taipei, Taiwan
2 Department of Medicine, Mackay Medical College, 252 New Taipei City, Taiwan
3 Division of Thoracic Surgery, Department of Surgery, Taipei Hospital, Ministry of Health and Welfare, 242 New Taipei City, Taiwan
4 School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, 112 Taipei, Taiwan
5 Center for General Education, Kainan University, 338 Taoyuan City, Taiwan
6 Department of Medical Research, National Taiwan University Hospital, 100 Taipei, Taiwan
7 Center for Mitochondrial Medicine and Free Radical Research, Changhua Christian Hospital, 500 Changhua City, Taiwan
8 Division of Allergy, Immunology & Rheumatology, Department of Medicine, Taipei Veterans General Hospital, 112 Taipei, Taiwan
9 Division of Immunology and Rheumatology, Fu-Jen Catholic University Hospital and School of Medicine, Fu-Jen Catholic University, 242 New Taipei City, Taiwan
*Correspondence: (Chang-Youh Tsai); (Yau-Huei Wei)
These authors contributed equally.
Academic Editor: Pietro Gentile
Front. Biosci. (Landmark Ed) 2022, 27(12), 333;
Submitted: 26 September 2022 | Revised: 7 December 2022 | Accepted: 8 December 2022 | Published: 27 December 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: The roles of plasma cell-free (pcf) mitochondrial DNA (mtDNApcf) and nuclear DNA (nDNApcf) in the pathogenesis of systemic lupus erythematosus (SLE) remain unclear. We analyzed the relative copies of mtDNApcf and nDNApcf and investigated their association with the levels of plasma 8-hydroxy-2’-deoxyguanosine (8-OHdG), plasma malondialdehyde (MDA) and mRNA of leukocyte C-type lectin domain family 5 member A (CLEC5A) in SLE patients. Methods: A total of 80 SLE patients and 43 healthy controls (HCs) were enrolled. Their plasma samples were subjected to the measurements of mtDNApcf copies, nDNApcf copies, 8-OHdG and MDA, respectively. Their leukocytes were analyzed for CLEC5A mRNA expression. Results: SLE patients had higher nDNApcf copies (2.84 ± 1.99 vs. 2.00 ± 0.88, p = 0.002), lower mtDNApcf copies (4.81 ± 6.33 vs. 9.83 ± 14.20, p = 0.032), higher plasma 8-OHdG (0.227 ± 0.085 vs. 0.199 ± 0.041 ng/mL, p = 0.016), lower plasma MDA (3.02 ± 2.20 vs. 4.37 ± 2.16 μM, p = 0.001) and similar leukocyte CLEC5A mRNA expression levels (1.21 ± 1.17 vs. 1.26 ± 1.05, p = 0.870), as compared with those of HCs. Among the HCs, SLE patients with SLE Disease Activity Index (SLEDAI) 8, and SLE patients with SLEDAI >8, their respective mtDNApcf copies decreased stepwisely (9.83 ± 14.20 vs. 6.28 ± 7.91 vs. 3.19 ± 3.35, p = 0.054). The nDNApcf copies of HCs, SLE patients without nephritis, and SLE patients with nephritis were increased stepwisely (2.00 ± 0.88 vs. 2.63 ± 1.74 vs. 3.16 ± 2.34, p = 0.043). Among SLE patients, higher nDNApcf copies were associated with higher levels of plasma 8-OHdG (p < 0.001) but lower plasma MDA (p = 0.019). Among HCs but not SLE patients, higher nDNApcf copies (p = 0.013) or lower mtDNApcf copies (p < 0.001) were related to higher levels of leukocyte CLEC5A mRNA expression. Conclusions: Higher nDNApcf, lower mtDNApcf, increased ROS-elicited oxidative DNA damage and dysregulated leukocyte CLEC5A expression might be implicated in the pathogenesis of SLE.

plasma cell-free mitochondrial DNA (mtDNApcf)
plasma cell-free nuclear DNA (nDNApcf)
malondialdehyde (MDA)
8-hydroxy-2'-deoxyguanosine (8-OHdG)
C-type lectin domain family 5 member A (CLEC5A)
systemic lupus erythematosus (SLE)
MOST 111- 2320-B-371-001/Ministry of Science and Technology
110-CCH-MST- 127/Changhua Christian Hospital
NSC102-2314-B-195-020/National Science Council
Fig. 1.
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