Autoantibodies to double-stranded DNA-Intermethod comparison between four commercial immunoassays and a research biosensor-based device

Abstract

Patients with systemic lupus erythematosus (SLE) often develop a wide variety of serological manifestations including the presence of antibodies to double-stranded DNA (anti-dsDNA). Positivity for anti-dsDNA constitutes one of the laboratory criteria for the diagnosis of SLE and is therefore clinically relevant. We analyzed the diagnostic accuracies of four commercial anti-dsDNA immunoassays and compared the results with a recently established surface plasmon resonance (SPR) biosensor chip with covalently chip-immobilized dsDNA. The anti-dsDNA measurements were performed retrospectively in 50 patients with clinically proven SLE, 39 patients with other autoimmunopathies and 20 healthy controls. Data were evaluated by Receiver-Operator Characteristic (ROC) analysis, with special regard to SLE patients suffering from lupus nephritis. The ROC analyses for the four immunoassays and the SPR biosensor resulted in the following area-under-the-curve (AUC) and diagnostic efficiency (DE) values in descending order: Bindazyme AUC, 0.89; DE, 0.88; ELiA AUC, 0.89; DE, 0.86; SPR biosensor AUC, 0.82; DE, 0.80; Farrzyme AUC, 0.77; DE, 0.77; Farr AUC, 0.77; DE, 0.70. When considering the 22 nephritis SLE patients the following AUC were observed: Bindazyme 0.98; EliA 0.95; SPR biosensor 0.93; Farr 0.89; Farrzyme 0.88. Although various methodologies for the determination of anti-dsDNA were compared, the overall diagnostic accuracy was found satisfactory in all immunoassays. Best data were found for the Bindazyme assay. We referenced the measurements to our in-house SPR biosensor device which showed good AUC and DE values. When optimized, this technique, allowing to monitor antigen/ antibody interactions in real-time, may add a new analytical quality to the existing methods, potentially beneficial in diagnosis and clinical monitoring of SLE.

An ENU Mutagenesis-Derived Mouse Model with a Dominant Jak1 Mutation Resembling Phenotypes of Systemic Autoimmune Disease

“…3,48,49 Consistent with the skin phenotype, the Jak1 S645Pþ/À mice showed a global increase of immunoglobulin isotype levels and autoDNA antibodies in circulation. These features are typical findings in patients with SLE, 50 with a more pronounced increase in females, 51 because we also observed them in female Jak1 S645Pþ/À mice mimicking the human situation.…”

Clinical Comparison of QUANTA Flash dsDNA Chemiluminescent Immunoassay with Four Current Assays for the Detection of Anti-dsDNA Autoantibodies

“…Various commercial ELISA tests are available through numerous companies. Although based on the same technology, poor agreement can be observed, as seen in previous studies [ 14 , 15 , 19 , 20 ]. Similar to the sensitivity observed for BioPlex 2200 dsDNA in this study, the sensitivity in SLE found for the two ELISAs was lower than previous studies [ 21 , 22 ], indicating that the SLE sample population for this study could be the reason.…”

“…As ELISAs are only moderately fast with assay times between 1.5 and 3 hours, the focus has lately shifted towards a decrease in assay time and ease of use. Despite significant technological advances, controversies persist on the method of choice for the detection of these antibodies [ 4 , 14 ]. The BioPlex 2200 dsDNA assay has been compared to other assays (Farr and Farrzyme) in a recent study [ 15 ].…”

“…Lastly, the Farr assay has been considered as the “gold standard” for the detection of anti-dsDNA antibodies [ 4 , 6 , 7 ]. However, not in all studies, the Farr assay was superior to other methods for the detection of anti-dsDNA antibodies and the discrimination of SLE and controls [ 14 ]. Additionally, in many countries, laboratories are switching from the Farr assay to fully automated solutions, which is largely due to the radioactive nature of the Farr assay [ 4 , 5 ].…”

Antigen-induced arthritis in rabbits: a comparative study between high-resolution ultrasound and contrast-enhanced ultrasound and pathologic findings

“…ROC curves can also be used to compare the diagnostic performance of two or more laboratory or diagnostic tests. A rough guide of AUC for classifying the accuracy of a diagnostic test is the traditional academic point system: 0.90-1 = excellent, 0.80-.090 = good, 0.70-0.80 = fair, 0.60-0.70 = poor, 0.50-0.60 = fail [17,18]. The AUC was 0.940-0.962, when an ROC curve was plotted depending on diagnosis of synovitis based on the thickness of SB and PC, indicating the measurement of the joint capsule with high-resolution ultrasound has a higher power of test and can be viewed as a good evidence for determining modeling success.…”