Clinical phenotype associations with various types of anti-dsDNA antibodies in patients with recent onset of rheumatic symptoms. Results from a multicentre observational study

Abstract

Despite anti-dsDNA antibodies constitute a wide range of specificities, they are considered as the hallmark for systemic lupus erythematosus (SLE).ObjectiveTo identify clinical phenotypes associated with anti-dsDNA antibodies, independently of any clinical diagnoses.MethodsPatients with recent onset of any rheumatic symptoms were screened for antinuclear antibodies (ANA). All ANA-positive and matching ANA-negative patients were examined, and their clinical phenotypes were registered, using a systematic chart formulated after consensus between the participating centres. All patients were tested for different anti-dsDNA antibody specificities with assays habitually used in each participating laboratory. Crithidia Luciliae Immuno Fluorescence Test (CLIFT) was performed three times (with two different commercial kits); solid and solution phase ELISA were performed four times. Associations between clinical phenotypes and results of anti-dsDNA assays were evaluated by linear regression analysis (LRA) and principal component analysis (PCA).ResultsTotally, 292 ANA-positive and 292 matching ANA-negative patients were included in the study. A full dataset for statistical analysis was obtained in 547 patients. Anti-dsDNA antibodies were most frequently detected by ELISA. LRA showed that overall positivity of anti-dsDNA antibodies was associated with proteinuria and pleuritis. Alopecia was significantly associated only with CLIFT-positivity. Besides confirming the same findings, PCA showed that combined positivity of CLIFT and ELISA was also associated with lymphopenia.ConclusionsOur results show that different anti-dsDNA antibody specificities are associated with nephropathy, pleuritis, alopecia and lymphopenia, regardless of the diagnosis. It may challenge the importance of anti-dsDNA antibodies as a diagnostic hallmark for SLE.

Natural killer cell expression of Ki67 is associated with elevated serum IL-15, disease activity and nephritis in systemic lupus erythematosus

“…While the etiology of SLE is unclear, B cells are a critical component of disease pathogenesis [37]. In turn, high titers of dsDNA autoantibodies have been shown to correlate with renal involvement [38,39]. Here we show that activated NK cells correlate significantly with the presence of CD11c hi B cells, plasma cells and serum anti-dsDNA autoantibodies.…”

Antinuclear Antibody–Negative Systemic Lupus Erythematosus in an International Inception Cohort

“…Thus, the detection of anti‐dsDNA antibodies even in ANA‐negative cases is still important and may aid in risk assessment for clinical complications. Furthermore, the anti‐dsDNA repertoire is diverse, such that there is no current anti‐dsDNA assay that is able to detect all of the subpopulations of anti‐dsDNA autoantibodies . Overall, the reports of anti‐dsDNA–positive/ANA‐negative sera found in the literature provide evidence that not all anti‐dsDNA antibodies are detected on conventional HEp‐2 substrates and that unique dsDNA epitopes may be missed by HEp‐2 IIF screening tests.…”

The anti-DNA antibody: origin and impact, dogmas and controversies

“…Furthermore, no widely accepted assay exists for the detection of anti-dsDNA antibodies in a classification context. Several comparative studies on anti-dsDNA antibody assays have been published (reviewed elsewhere 72,73,[92][93][94] ). Some of these assays claim to detect high-avidity or low-avidity antibodies, but not only is the term avidity in this context vague, how the avidity or intrinsic affinity (which is a concise measure) is d etermined also remains unclear.…”

“…59 In the clinical context, these differences in structure are apparent from the fact that many antibodies described in patients with SLE bind elongated B-DNA in different versions of ELISA, whereas other anti bodies bind covalently closed circular plasmid dsDNA in ELISAs, or the highly bent Crithidia luciliae kinetoplast DNA. 72,73 As the frequency of antibodies that bind elongated B-DNA is higher than those that bind highly bent dsDNA, 72-74 the ability to control immune tolerance for B-DNA might depend on the DNA structures present in the nucleosome. 75 A wider autoimmune response To explain the genesis of anti-B-DNA antibodies in vivo, the context in which the immunogen is presented to the immune system is an important consideration.…”