Background/Purpose:

Anti-dsDNA antibodies support the diagnosis of
systemic lupus erythematosus (SLE), and their quantification is useful for the
assessment of lupus nephritis (LN) and the disease activity in LN patients. However,
the standardization of anti-dsDNA antibodies in terms of diagnostic accuracy
and utility to measure disease activity is still poor and different test
systems yield different results. Using a large cohort of well characterized SLE
patients, we analyzed the usefulness of a novel anti-dsDNA microparticle
chemiluminescent immunoassay (CIA) for the
association with LN, and compared the assay to two traditional ELISA methods.

Methods:

Samples from 457 SLE patients from three cohorts
(Canada, Spain, USA) were tested with the QUANTA Flash
dsDNA CIA (Inova Diagnostics, San Diego, USA). Of
these 457 SLE patients, 132 (28.9%) had LN at the time of the blood draw, or
had the history of LN. Data obtained with the QUANTA Lite dsDNA SC ELISA and
with the QUANTA Lite HA dsDNA ELISA (Inova
Diagnostics) were available for samples from the Canadian and USA cohort
(n=305), and results obtained with the HA dsDNA ELISA were available for
samples from the Canada cohort only (n=234). The data were statistically
evaluated using Analyse-it software (Version 3.90.1;
Leeds, UK). Wilcoxon-Mann-Whitney was used to analyze the titer difference
between different groups. Fisher Exact test was used to analyze antibody
prevalence in different categories and p
values < 0.05 were considered significant for all statistical methods.

Results:

In the total
SLE group (n=457), the dsDNA CIA was positive in 59.3% of all SLE patients and
in 70.5% with LN (n=132) (Fisher Exact p=0.002
compared to non-LN SLE). Anti-dsDNA antibody levels, as measured by CIA were
significantly higher in LN patients compared to the rest of the SLE patients
(median 67.5 vs. 32.4 IU/mL; p<0.0001, See Table). SLE patients
who tested positive on CIA had an odds ratio (OR) of 2.0 (95% Confidence
Interval, CI 1.3-3.0) for LN. Within the Canadian cohort, there was a
significant difference between active vs.
inactive LN for both the prevalence (p=0.0170)
and the level (median 50.0 vs. 28.7
IU/mL; p=0.0160) of anti-dsDNA
antibodies. When compared to the ELISA methods, the dsDNA CIA results showed
the strongest correlation with LN (See Table).

*NOTE: NS = not significant. A p-value greater than 0.05 was considered not significant.

Conclusion:

Our results
show that the measurement of anti-dsDNA antibodies obtained with the dsDNA CIA
is superior to other more conventional assays for the occurrence of LN and
assessment of active disease in LN patients.