The Prevalence of Anti-DFS70 Antibodies in an International Inception Cohort of Systemic Lupus Erythematosus

Abstract

Background/Purpose: Autoantibodies to the nuclear autoantigen dense fine speckles 70 (DFS70) are associated with a new paradigm whereby when they are found in isolation (monospecific – no other detectable autoantibodies), they are purported to rule out the diagnosis of systemic lupus erythematosus (SLE) and other anti-nuclear antibody (ANA)-related conditions. Anti-DFS70 can be screened by indirect immunofluorescence (IIF) and quantified and confirmed by chemiluminescence immunoassay (CIA). The reported frequency of anti-DFS70 by CIA in SLE is low compared to healthy individuals (0-6% vs. 7-20%). Furthermore, anti-DFS70 monospecificity is reported to be low in SLE patients (<1%). To date, there have been no studies examining the frequency of anti-DFS70 in early inception SLE cohorts. The purpose of this study was to determine the prevalence of anti-DFS70 in newly diagnosed SLE patients and to identify any univariate associations with demographic and clinical features.

Methods: Patients fulfilling the American College of Rheumatology (ACR) Classification Criteria for SLE were enrolled in the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Demographic and clinical data, including disease activity (SLEDAI-2K), were collected at enrollment. ANAs were detected by IIF on HEp-2 cells (ImmunoConcepts, Sacramento, CA), and extractable nuclear antigens (ENAs) and double-stranded DNA (ds-DNA) by an addressable laser bead immunoassay (FIDIS Connective 13, TheraDiag, Paris). Anti-DFS70 antibodies were measured by CIA using cutoffs suggested by the manufacturer (Inova Diagnostics Inc., San Diego, CA).

Results: 1137 patients were included; 89.4% were female and 94.4% were ANA IIF positive (Table 1). The frequency of anti-DFS70 by CIA was 7.1% [95%CI: 5.7-8.8%] (81/1137 patients). 11/1137 (0.97%) [95%CI: 0.5-1.7%] of the entire cohort were positive for anti-DFS70 only with no detectable ENA or anti-dsDNA and were therefore considered ÔmonospecificÕ for anti-DFS70. Patients with a negative anti-DFS70 by CIA were more likely than those with a positive anti-DFS70 to have other SLE-related autoantibodies including anti-U1-RNP (31.5% vs. 21.0%), anti-Ro60 (46.3% vs. 34.6%), and anti-SSB (16.0% vs. 4.9%). Age, gender, ethnicity, disease features included in the ACR classification criteria, SLEDAI-2K score, or concomitant therapies did not differ between the anti-DFS70 negative and positive patients.

Conclusion: The prevalence of anti-DFS70 measured by CIA in newly diagnosed SLE patients was at the high end of the range as compared to that in previously published SLE cohorts (7.1% vs. 0-6%). However, “monospecific” anti-DFS70 was rare (0.97%) in this SLE inception cohort and, therefore, the presence of monospecific anti-DFS70 is a potentially useful test to discriminate between ANA positive healthy individuals and those newly diagnosed with definite SLE.