Neutrophil extracellular trap mitochondrial DNA and its antibody are correlated with clinical features of patients with systemic lupus erythematosus / 中华风湿病学杂志

ABSTRACT

Objective To correlate the neutrophil extracellular trap (NET) mitochondrial DNA (mtDNA) and anti-mtDNA antibodies (Abs) with disease activity and clinical features in systemic lupus erythematosus (SLE) patients.Methods We enrolled 102 SLE patients,rheumatoid arthritis (RA) patients (n=30) and healthy donors as controls (n=40).NET were generated from phorbol 12-myristate 13-acetate (PMA)-stimulated peripheral neutrophils.mtDNA levels and the transcriptional levels of five interferon inducible genes(IFIGs)(OAS-1,Mx-1,Ly6e,IFIT1 and IFIT4) were measured by quantitative PCR.Interferon scores (IFN scores) were calculated.Anti-mtDNA Abs were detected by enzyme-linked immunosorbent assay.Spearman's correlation analysis,t test andx2 test were used for statistical analysis.Results mtDNA release by netting neutrophils was greatly enhanced in SLE patients (1 088 000 ±1 133 000) compared with healthy controls (465 900±447 200)(t=2.617,P＜0.01) and significantly correlated with IFN scores (r=0.460 6,P＜0.01).NETs mtDNA in moderate active group (728 300±1 003 000) and severe active group (1 093 000±946 500) were significantly higher than the mild active group (159 500±155 100) (t=2.240,P＜0.05,t=3.894,P＜0.01).Forty-one percent of SLE patients were positive for anti-mtDNA Abs(1.28±0.68),while none of the healthy donors (0.70±0.31) (P＜0.01) and RA controls (0.59±0.18)(P＜0.01) displayed a positive serology response to mtDNA.Addition-ally,the titers of anti-mtDNA Abs were also associated with IFN scores (r=0.292 8,P＜0.05).Anti-mtDNA Abs in moderate active group (1.3±-0.6) and severe active group(1.4±0.7)were significantly higher than the mild active group (0.7±0.4) (t=3.154,3.538,all P＜0.01).The levels of anti-mtDNA Abs significantly correlated with classic an-ti-dsDNA Abs titers measured by Farr assay (r=0.542 9,P＜0.001) and were associated with LN (x2=8.644,P＜0.01).Conclusion mtDNA in NET and anti-mtDNA Abs serve as new biomarkers for disease activity and renal involvement in SLE patients.