Anti-nucleosome, anti-chromatin, anti-dsDNA and anti-histone antibody reactivity in systemic lupus erythematosus

Antinucleosome (antichromatin) antibodies play a key role in the pathogenesis of systemic lupus erythematosus (SLE). The objective of the present study was to determine the clinical significance of antinucleosome (antichromatin) antibodies, antidsDNA antibodies and antihistone antibodies in patients with SLE in relation to patients with positive nuclear antibodies and healthy controls. We measured antinucleosome (antichromatin) antibodies, antidsDNA antibodies and antihistone antibodies in 70 patients with SLE, 35 antinuclear antibody (ANA)positive subjects without autoimmune disease and 35 blood donors. All antibodies were determined by enzyme linked immunosorbent assay (ELISA). We obtained the receiver operating caracteristic (ROC) curve and the area under the curve (AUC) for each autoantibody. Likewise, we obtained the sensitivity, specificity and positive and negative likelihood ratios for each autoantibody. The highest AUC was obtained for antinucleosome (0.898) and the lowest AUC for a kit for antidsDNA (0.725). Stratification of the control group (ANApositive subjects without autoimmune disease and blood donors) produced significant changes in the AUCs; all AUCs decreased when ANApositive patients without autoimmune disease were considered as controls and all AUCs increased when blood donors were considered as controls. These effects were less marked in antidsDNA antibodies. We observed discrepancies between kits (antinucleosome and antichromatin and two for antidsDNA). The highest sensitivity for SLE was obtained for antinucleosome antibodies (86%) and the highest specificity was obtained for antidsDNA antibodies (90%). In conclusion, antinucleosome and antichromatin kits show different degrees of clinical accuracy due to the cutoff selected by the manufacturer. Once the kits with the best performance and the optimal cutoffs have been selected, antinucleosome antibodies and antidsDNA antibodies provide similar information in established SLE.