Oxidative DNA and mitochondrial DNA change in patients with SLE.
We evaluated plasma IL-10, IFN-alpha, IL-23, IFN-gamma, IP-10, MCP-1, 8-OHdG, leukocyte mtDNA, serum anti-dsDNA antibodies and disease activity index (SLEDAI) in SLE patients. 93 patients (35 nephritis, 4 under dialysis, 5 under rituximab) and 50 healthy controls were recruited. Compared with healthy controls, SLE patients had higher IL-10, IFN-alpha, IL-23, IFN-gamma, IP-10 and MCP-1 (p<0.05). High IFN-alpha (p=0.031) and IP-10 (p=0.026) correlated with high SLEDAI; high IFN-alpha (p<0.001), IL-23 (p=0.023) and IP-10 (p<0.001) correlated with high anti-dsDNA. High IL-10 (p=0.014), IL-23 (p<0.001), IFN-gamma (p<0.001) and MCP-1 (p=0.002) correlated with high 8-OHdG and high IL-23 (p<0.001), INF-gamma (p<0.001), IP-10 (p=0.023) and MCP-1 (p=0.002) correlated with low leukocyte mtDNA. mtDNA 4977 deletion correlated with high mtDNA (p=0.011) and low IL-10 (p=0.009). MCP-1 (p=0.043) decreased after rituximab therapy. 54 SLE patients without nephritis, 35 with nephritis but without dialysis, and 4 with nephritis under dialysis exhibited stepwise increases in IL-23 (p=0.009) and MCP-1 (p=0.015). These data suggest that oxidative DNA and mtDNA alterations and coordinate changes in cytokines/chemokines are implicated in progression of SLE and rituximab in amelioration of SLE.
Division of Allergy, Immunology & Rheumatology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan and Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
Hui-Ting
HT
Lee
Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan and Division of Nephrology, Taipei Veterans General Hospital, Taipei, Taiwan.
Tsai-Hung
TH
Wu
Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan and Division of Thoracic Surgery, Feng-Yuan Hospital, Ministry of Health and Welfare, Taichung City, Taiwan.
Chen-Sung
CS
Lin
Division of Allergy, Immunology & Rheumatology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan and Mackay Junior College of Medicine, Nursing, and Management, New Taipei City, Taiwan.
Chyou-Shen
CS
Lee
Division of Allergy, mmunology & RheumatologyI, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan and Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
Siao-Cian
SC
Pan
Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan and Division of Allergy, Immunology and Rheumatology, Taipei Veterans General Hospital, Taipei, Taiwan.
Deh-Ming
DM
Chang
Department of Medicine, Mackay Medical College, New Taipei City, Taiwan and Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.
Yau-Huei
YH
Wei
Division of Allergy, Immunology & Rheumatology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan,, cytsai@vghtpe.gov.tw.
Chang-Youh
CY
Tsai
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000974:Antibodies, Antinuclear / Q000097:blood; D016022:Case-Control Studies; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D004272:DNA, Mitochondrial / Q000097:blood* / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D018450:Disease Progression; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000235:genetics / Q000276:immunology; D008297:Male; D017384:Sequence Deletion
D000974:Antibodies, Antinuclear; D018925:Chemokines; D016207:Cytokines; D004272:DNA, Mitochondrial; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine