Understanding ANA Test "False Positive" Readings

Researchers from Brazil recently uncovered distinguishing characteristics of the antinuclear antibodies (ANA) test in healthy individuals and patients with autoimmune disease, reducing the likelihood of an erroneous autoimmune disorder diagnosis.

Their findings are published in the January 2011 issue of Arthritis & Rheumatism, a journal of the American College of Rheumatology (ACR)

The presence of ANA typically indicates the possibility of autoimmunity. To detect ANA, medical professionals usually use the indirect immunofluorescence (IIF) assay on HEp-2 cells as the standard blood test (ANA-HEp-2). However, studies have revealed that a "false-positive" ANA test occurs in up to 13% of healthy individuals.

The Brazilian research team, led by Luis Andrade, MD, PhD, from the Federal University of São Paulo, recruited 918 healthy individuals (634 females and 284 males) between the ages of 18 and 66 for this study. In the control group, 153 patients with autoimmune rheumatic diseases that included lupus (87), systemic sclerosis (45), Sjögren's syndrome (11) and idiopathic inflammatory myopathy (10) were included. To determine the concentration of ANA in the blood, ANA-HEp-2 tests were run on all participants and considered positive if a well defined IIF pattern was identified.

"The ANA-HEp-2 test is positive in a sizable portion of the general population and our findings established distinguishing characteristics between healthy individuals and patients with autoimmune disease which is essential to accurately interpret the test results," Andrade said, in a press release. Researchers determined that positive ANA-HEp-2 tests in healthy participants occurred predominantly as a nuclear fine speckled (NFS) pattern (at low to moderate titer) or as a nuclear dense fine speckled (NDFS) pattern (frequently at high titer) in 46% and 33% of ANA-positive healthy individuals, respectively. Healthy participants did not present a nuclear coarse speckled (NCS) or a nuclear homogeneous (Ho) pattern.

In those with autoimmune disease the ANA-HEp-2 showed positive results at a predominantly moderate to high titer. A distinct ANA-HEp-2 pattern profile was observed, characterized by the absence of the NDFS pattern and the exclusive occurrence of the NCS (26%), centromeric (8%), nuclear homogeneous (7%), and cytoplasmic dense fine speckled (3%) patterns. ANA-positive patients with confirmed autoimmune diseases also showed the presence of the NFS (42%), but at a higher titer than in healthy individuals.

At the end of a 4-year follow-up period 73% of the ANA-positive healthy individuals retained a positive test result, but did not develop any symptoms of autoimmune rheumatic disease. "Our study confirms that the ANA-HEp-2 pattern is critical in properly diagnosing autoimmune disorders and future research should attempt to reproduce the interpretation of test results among different ANA experts and ANA-HEp-2 slides brands," Andrade said.

Sources: Wiley - Blackwell, AlphaGalileo Foundation--Will the findings impact future ANA test readings? Leave a comment.