No 11, 2012

Publication of the Month

 

 

November 11/12: 

anti-DFS70 antibodies

 

Key message:

  • Clinically false positive results in indirect immunofluorescence (IIF) on HEp-2 cells are often caused by anti DFS70 antibodies. The respective dense fine speckled (DFS) pattern is frequently found in apparently healthy individuals.
  • It is important to recognize this pattern and confirm the reactivity to DFS70 by a specific assay.
  • Anti-DFS70 antibodies should be considered in diagnostic algorithms of ANA testing.

Mahler M, Hanly JG, Fritzler MJ
Importance of the dense fine speckled pattern on HEp-2 cells and anti-DFS70 antibodies for the diagnosis of systemic autoimmune diseases
Autoim Rev 2012; 11: 642–645

Summary:
IIF on HEp-2 cells was recommended as the screening test as of choice for the detection of antinuclear antibodies by a task force of the ACR in 2010. However, up to 20% of serum samples from healthy individuals have been reported to have a positive ANA test. A specific IIF pattern, the dense fine speckles (DFS) pattern has been reported in 33% of ANA positive healthy individuals, but not in ANA positive sera from patients with systemic autoimmune diseases. In most cases, this pattern is due to antibodies reacting with the DFS70 antigen.
Since the intended use of the ANA HEp-2 test is to aid in the diagnosis of CTD, the reporting of the DFS pattern as a positive result, significantly reduces the specificity and the positive likelihood of the ANA test.

Conclusions:
Considering that anti-DFS70 antibody positivity is rare in patients with systemic autoimmune diseases, introducing the anti-DFS70 antibody examination as a screening test for ANA-positive persons could be used to rule out systemic autoimmune diseases, resulting in considerable cost-saving potential. However, not all sera demonstrating the DFS pattern are from healthy individuals. This underlines the importance of a better understanding of anti-DFS70 antibodies and the consideration and inclusion of anti-DFS70 in diagnostic algorithms or reflex testing approaches. Therefore, it is suggested that samples with a DFS staining pattern identified by IIF should then be tested for anti-DFS70 antibodies with a specific immunoassay and the test result should be reported and clearly explained to clinicians.

Comment:
The identification of anti-DFS70 in a sample could be a good hint for the clinician that there is a low risk of a systemic autoimmune disease, despite ANA positivity. However, the correct identification of the dense fine speckled pattern is not easy and depends on experienced technicians. No automated or digital system is currently available that is capable of differentiating the DFS IIF pattern from homogeneous or “quasi-homogeneous” patterns.

 

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As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.