Background/Purpose:

Anti-dsDNA antibodies are highly specific for systemic lupus erythematosus (SLE) and often associate with lupus nephritis. Extracellular nucleosome DNA released from apoptotic or necrotic cells are thought to be the source of DNA autoantigens in SLE. Recent studies show that mitochondria DNA (mtDNA) may play an important role in driving the production of anti-DNA autoantibodies and type I interferons in SLE. Since mtDNA are rich in unmethylated CpG islands, mtDNA may represent a distinct class of autoantigens in SLE. The purpose of this study was to compare autoantibodies to mtDNA and nucleosome-associated DNA in SLE and their association with lupus nephritis and other disease parameters.

Methods:

144 patients who fulfilled the 1997 American College of Rheumatology criteria for SLE were recruited at the University of Nebraska Medical Center (UNMC). 123 healthy controls (matched with SLE patients in demographics, about 80% female with an average age of 37, about 50% Caucasians, 30% African Americans, and 15% Hispanic) were recruited at the community of UNMC. Blood serum samples were tested for anti-mtDNA antibodies using Enzyme-linked immunosorbent assay (ELISA) with PCR-amplified human mtDNA as the capturing antigen. The anti-dsDNA NcX antibodies were determined using ELISA-based kit from Euroimmun. The data were summarized from three independent experiments.

Results:

The anti-mtDNA antibodies are significantly higher in patients with SLE (n = 144, mean optical density units OD = 0.80; SD = 0.90) than healthy controls (n = 123, mean OD = 0.19; SD = 0.11) with a p value less than 0.0001 (by two-tailed Mann-Whitney test). Using the mean + 2 x SD of healthy controls as the cut off for positivity, 51.4% of SLE patients are tested positive for anti-mtDNA antibodies while 41% of the same SLE cohort are tested positive for anti-dsDNA-Ncx. Anti-mtDNA antibody levels are also more significantly correlated with SLEDAI (Pearson r = 0.53, p = 0.0001), and reversely correlated with C3 and C4 levels (Pearson r = -0.4, p = 0.0001; Pearson r = 0.21 , p = 0.01, respectively) than anti-dsDNA-NcX antibody levels. Furthermore, increased percentage of SLE patients with active lupus nephritis were tested positive for anti-mtDNA (65%) than anti-dsDNA NcX (52%).

Conclusion:

We have developed a simple anti-mtDNA ELISA assay that has 10% higher sensitivity for SLE and 13% higher sensitivity for active lupus nephritis, compared to the widely used anti-dsDNA NcX ELISA assay (Euroimmun). The anti-mtDNA antibodies also have better correlations with SLEDAI, C3, and C4 levels. Therefore, anti-mtDNA antibody may serve as an improved biomarker for SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-mitochondria-dna-antibody-as-an-improved-biomarker-for-systemic-lupus-erythematosus/