How useful is anti-DFS70 in identifying ANA-positive patients without SARD?

A Singapore study has found an association between the presence of anti-DFS70 and a false-positive antinuclear antibody (ANA) test in 8.6 percent of its patients. Moreover, anti-DFS70 shows no association with the absence of systemic autoimmune rheumatic disease (SARD).

“The association of anti-DFS70 with disease remains debatable,” the researchers said. “Reports of associated diseases include systemic lupus erythematosus (SLE), Sjögren’s syndrome (SS), undifferentiated connective disease, Hashimoto’s thyroiditis, Grave’s disease, alopecia areata, multiple sclerosis, and Vogt-Koyanagi-Harada syndrome.” [J Rheumatol 2012;39:2104-2110]

In the present study, the researchers retrospectively analysed patient samples obtained for ANA testing from 1 January 2016 to 30 June 2016. These samples underwent ANA testing via indirect immunofluorescence method and anti-DSF70 testing using enzyme-linked immunosorbent assay.

A total of 645 ANA-positive samples were analysed, of which 41.7 percent were positive at a titre of 1:80. The most common nuclear straining pattern was speckled (65.5 percent). Of the ANA-positive patients, only 9.5 percent were diagnosed with SARD, and 10.0 percent were found to have anti-DFS70. Most patients (86.4 percent) had no SARD. [Singapore Med J 2022;63:147-151]

There were seven patients with positive ANA titre >1:640, the presence of antidouble stranded DNA, and/or anti-Ro60. Of note, the presence of anti-DFS70 in ANA-positive patients did not correlate with the absence of SARD (Fisher’s exact test, p=0.245).

“Our study demonstrated a lower prevalence (nearly one-tenth) of anti-DFS70 among our ANA-positive patients than what has been reported in the literature,” the researchers said. “One possible explanation for this could be the unselected use of the test in a general population.” [Arthritis Rheum 2004;50:892-900]

Polarizing views

Over the last 20 years, the body of evidence contributed to opposing views regarding the use of anti-DFS70 testing. Those who disagree think that the test has little discriminatory value in identifying health from disease, given its prevalence in a variety of chronic inflammatory diseases, cancer types, SARDs, and in healthy individuals.

Proponents of anti-DFS70 testing, on the other hand, push for the adoption of the autoantibody in routine disease-specific autoantibody testing after a positive ANA test, because healthy individuals who are ANA-positive tend to be “monospecific” for anti-DFS70.

“This means that ANA-positive healthy individuals only demonstrate positivity to anti-DFS70, without any coexisting disease-specific autoantibodies, such as anti-dsDNA, anti-Ro, and other extractable nuclei antibodies,” the researchers said. [J Rheumatol 2012;39:2104-2110]

“The addition of anti-DFS70 to a test panel would, thus, have discriminatory value between disease and nondisease states,” they added.

An earlier study also suggested that the inclusion of anti-DFS70 into ANA testing algorithms is cost-effective, reducing unnecessary specialist clinical referrals and follow-up. [Auto Immun Highlights 2016;7:10]

“Manufacturers of commercial autoantibody test assays appear to subscribe to the proposing view and have adopted the anti-DFS70 test,” the researchers said. “Numerous commercial anti-DFS70 assays can now be found utilizing a variety of immunoassay techniques, including ELISA, CLIA, and line immunoassay.”