Background/Purpose:

 Historically, Immunofluorescence Assay (IFA) methodology has been the gold standard for ANA screening. Most clinical laboratories in recent years utilize the Enzyme Linked Immunoassay (ELISA) to screen for ANA rather than IFA as ELISA is automated and less expensive. Studies have suggested the sensitivity and specificity of the two methods are comparable but most of these studies were retrospective and not done in populations of patients referred to rheumatologists. There has been concern among rheumatologists that there may be a high “false negative” rate for ELISA when compared to IFA, potentially affecting a rheumatologist’s ability to diagnose patients with connective tissue disorders. We studied the incidence and clinical relevance of a negative ANA by ELISA when the IFA is positive and when ordered by a rheumatologist.

Methods:

 We conducted a prospective study in a 12 person integrated health system rheumatology practice to determine the rate of “false negative” ANA by ELISA. 200 consecutive negative ELISA ANA’s ordered by rheumatologists were subsequently reanalyzed with IFA. We reviewed medical records of these patients and surveyed their rheumatologists regarding the clinical relevance of the positive IFA ANA finding for each patient identified. After their experience with the “false negative” ELISA and after providing the rheumatologists with the lab’s comparative costs of the 2 methodologies, their opinion about the most cost effective ANA screening strategy was solicited.

Results:

Of 200 consecutive ELISA negative ANA’s ordered by rheumatologists reanalyzed using IFA, 15% were positive by IFA. Six% had titers of 1:160 or greater. One was 1:10240. The rheumatologist survey demonstrated that of the 30 patients with false negative ANA by ELISA, the clinical suspicion of an underlying connective tissue disorder remained medium or high in 17 despite the negative ANA. In 8 patients, the clinical suspicion for a connective tissue disorder increased following the finding of a positive ANA by IFA and in 4 patients led to additional testing or start of treatment for a connective tissue disorder. The surveyed rheumatologists by a large majority felt that the abnormal ANA cut off titer should remain 1:160. After experience with each “false negative” ELISA patient and after being provided with cost differences for the IFA and ELISA methodologies, the rheumatologists by a slim majority (14 to 13) recommended continuation of the current lab’s practice of screening all ANAs with ELISA rather than the option of screening rheumatology ordered ANAs with IFA (added lab cost $3,323.50/yr.) No one felt the entire system’s ANAs screening should be done by IFA (added cost to lab $33,465.20/yr.)

Conclusion:

Use of IFA rather than ELISA as initial screening ANA test would rarely change a rheumatologist’s patient management decisions. With knowledge of the “false negative” ELISA rate, the system’s cost differences between the ELISA and IFA, and experience with their own patients who have had a “false negative”, rheumatologists in an integrated health system prefer the ELISA methodology over IFA as initial ANA screen.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-clinical-relevance-of-a-false-negative-enzyme-linked-immunoassay-which-antinuclear-antibody-screening-test-is-preferred-by-rheumatologists-in-an-integrated-health-system/