The findings of a new study challenge the importance of anti–double stranded DNA antibodies as a diagnostic hallmark for lupus.
The assessment of different anti–double stranded DNA (dsDNA) antibody specificities using different techniques in patients testing either positive or negative for antinuclear antibodies (ANA) resulted in a “considerable discrepancy of outcomes and correlations to clinical and biochemical manifestations,” said an international team of researchers led by Dr. Michele Compagno of Lund University in Sweden.
Although anti-dsDNA antibodies are regarded as fairly specific for systemic lupus erythematosus (SLE), the pathogenic and diagnostic roles they play are still debated. It’s also unclear whether SLE represents one disease entity or is a continuous overlap of etiologically unrelated organ manifestations, making it particularly challenging to determine biomarkers for the disease, the researchers wrote (Lupus Sci. Med. 2014;1:e000007 [doi:10.1136/lupus-2013-000007]).
Dr. Compagno and her associates therefore aimed to correlate the presence of anti-dsDNA antibodies with individual clinical manifestations and laboratory variables in patients with recent-onset rheumatic symptoms, regardless of their diagnosis.
“By this approach, we aimed to reproduce the usual clinical setting, where the physician, at an early stage, is challenged to formulate a diagnosis and predict the outcome, based on clinical manifestations and suitable diagnostic tools available locally,” they wrote.
For the multicenter observational study, 292 ANA-positive and 292 sex- and age-matched ANA-negative patients were tested for different anti-dsDNA antibody specificities with assays commonly used in laboratories.
The discrepancies between outcomes and correlations to clinical phenotypes and biochemical profiles included, for example, anti-dsDNA antibodies that were associated with the presence of proteinuria, regardless of clinical diagnosis, outcome of ANA screening, and assay and technique used.
Also, in distinct subgroups of patients, the antibodies were variously associated with hematuria, leukopenia, pleuritis, and alopecia. The study results provided clinical support for Crithidia Luciliae Immunofluorescence Test (CLIFT)–determined anti-dsDNA antibodies, but only in a limited number of key SLE manifestations.
The findings also challenged the broad role of enzyme-linked immunosorbent assay–based anti-dsDNA antibody testing in diagnosis and classification of SLE, according to the investigators.
“The data support the notion that various anti-dsDNA antibodies impact differently on the classification of SLE,” they said.
“These observations raise the discussion about the performance of the various anti-dsDNA detection techniques, the general pathogenic role of the various anti-dsDNA antibodies identified, their clinical associations, and how the syndrome of SLE is currently delineated,” they concluded.
The study was supported by a variety of patient-advocacy organizations and research foundations. The study authors declared having no competing interests.