Decreases in anti-double-stranded DNA levels are associated with concurrent flares in patients with systemic lupus erythematosus

Objective. To determine the degree to which changes in anti-double-stranded DNA (anti-dsDNA), as determined by Crithidia and enzyme-linked immunosorbe nt assays (ELISAs), precede or coincide with changes in systemic lupus eryt hematosus (SLE) activity, as measured by 5 clinical indices, the physician' s global assessment (PGA), modified SLE Disease Activity Index (M-SLEDAI), modified Lupus Activity Index (M-LAI), Systemic Lupus Activity Measure (SLA M), and the modified British Isles Lupus Assessment Group (M-BILAG). Methods. Disease activity and anti-dsDNA were measured monthly in 53 SLE pa tients who were followed up for I year. Lupus flare was defined as an incre ase in PGA of greater than or equal to1.0, M-SLEDAI greater than or equal t o3, M-LAI greater than or equal to0.1, SLAM greater than or equal to3, and M-BILAG A within a I-month period. Flare rates were calculated for groups, which were defined by "previous" (1 month prior to the flare) or "concurren t" (at the time of the flare) changes in anti-dsDNA. Logistic regression mo dels were used to determine the significance of the association between rec ent changes in anti-dsDNA and flare, controlling for the prednisone dosage. Results. Flares occurred at 12% of visits, based on the PGA measure of dise ase activity. Using the other indices, flare rates were 19% (M-SLEDAI), 25% (M-LAI), 13% (SLAM), and 12% (M-BILAG). A concurrent decrease in anti-dsDN A (ELISA) was associated with significantly higher flare rates based on PGA (18 of 84, 21%; P = 0.0014), M-SLEDAI (27 of 89, 30%; P = 0.0019), M-LAI ( 37 of 89, 42%; P = 0.0001), and M-BILAG (19 of 89, 21%; P = 0.0264) scores. Flare rates were also significantly higher after a previous increase in an ti-dsDNA (ELISA) based on M-SLEDAI (26 of 93, 30%; P = 0.0022) and M-LAI (3 4 of 93, 37%; P = 0.0117) scores. Flare rates tended to be lowest when ther e was a concurrent increase in anti-dsDNA (ELISA). Analysis of specific org an systems showed that a concurrent decrease in anti-dsDNA (ELISA) was sign ificantly associated with increases in renal disease activity. Similar resu lts were obtained using the Crithidia assay. Conclusion. A previous increase in anti-dsDNA levels occurred before SLE fl ares, as measured by the M-SLEDAI and M-LAI only. However, during lupus fla res, including the subset of renal flares, anti-dsDNA levels frequently dec reased. We hypothesize that this decrease in anti-dsDNA represents depositi on in tissue at the time of flare.