Monday, 10 Dec 2018

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Are ANA Tests Unreliable?

Pisetsky and colleagues have reported in the Annals of Rheumatic Disease that ANA tests done on established SLE patients may yield surprisingly disparate results.

While ANA negative lupus was a problem of old assays and the loss of ANA positivity may be seen with chronicity or age, most rheumatologists believe that ANA positivity is an absolute requirement for the diagnosis of systemic lupus erythematosus (SLE).

Researchers studied 103 patients with established SLE using three different immunofluorescence assays (IFA) for ANA determination. ANA determinations were also performed by an ELISA and bead-based multiplex assay.

With the IFA kits, ANA negativity was found in 4.9%–22.3% of serum samples. Moreover, the ELISA and multiplex assays found 11.7 to 13.6% seronegativity as well.

Patients with positive assays were more likely to have historic anti–double-stranded DNA positivity and low complement levels.

These findings raise numerous questions including whether these 5-22% of ANA seronegative lupus patients should be considered for clinical trials or managed differently.

Might these findings parallel that seen in rheumatoid arthritis with seronegative and seropositive populations?  While the overlap in treatment and outcomes is considerable, seropositivity (especially for ACPA) has the advantage of homogenizing the population under study.


The author has no conflicts of interest to disclose related to this subject

Rheumatologists' Comments

This is an important study done by recognized lupus experts. The question that I have is if all the SLE patient's who had sera tested were ANA positive at time of their original diagnosis. If so, then the question is at the time their sera was tested for this study, what treatment were they on and how active was their lupus. This was not included in this study. We have all had SLE patients who are well controlled on therapy and their ANA becomes negative. In my opinion, ANA negative patients either do not have SLE or are extremely well controlled on therapy and should not be included in lupus trials. Dr. Pisetsky does make a good point that all ANA assays are not equal in quality.
I very much appreciate Dr. West's comments on our study. In the study in ARD, we focused on kit variability. Ongoing studies are investigating possible determinants of any change in ANA status during the course of disease, recognizing potential differences among kits in ANA detection. We are very interested in those patients who become consistently ANA negative and, like Dr. West, wonder whether they still have SLE or should be in trials. The phenomenon of ANA negativity has not been well studied but is definitely worth attention as interest in remission in SLE grows.
What percentage of ANA negative patients on IFA may be due to prozone phenomenon (if dilution not done)? Also does significant proteinuria in nephritis patients alter the performance of the test and lead to negative results? Can these may be additional factors other than performance characteristics of the test kits per se.

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