Posted by Phillipa on January 13, 2011, at 22:15:57
Seems like a positive ANA doesn't always mean an autoimmune disorder. Phillipa
From Medscape Medical News
New ANA Test Helps Sort Out False Positives for Autoimmune Disorders
Janis C. KellyAuthors and Disclosures
January 12, 2011 â Up to 13% of healthy people test positive for antinuclear antibodies (ANA), which are associated with autoimmune disorders such as rheumatoid arthritis, Sjögren's syndrome, or systemic lupus erythematosus. Most of those healthy patients with positive results will not go on to develop autoimmune diseases, but sorting out the patients with false positives from those patients truly at risk has been difficult.
Now Henrique A. Mariz, MD, and colleagues, working with Luis E.C. Andrade, MD, PhD, from the Universidade Federal de São Paulo, Brazil, report that specific patterns on the immunofluorescent ANA-HEp-2 assay are strongly associated with autoimmune rheumatic diseases (ARD). The researchers hope that clinicians might be able to use these pattern differences to reduce the risk for an erroneous autoimmune disorder diagnosis.
The study, reported in the January issue of Arthritis & Rheumatism, enrolled 918 healthy individuals (634 women, 284 men) between the ages of 18 and 66 years and compared their blood tests with those from a control group of 153 patients with autoimmune rheumatic diseases. This group included patients with lupus (n = 87), patients with systemic sclerosis (n = 45), patients with Sjögren's syndrome (n = 11), and patients with idiopathic inflammatory myopathy (n = 10). ANA-HEp-2 tests were run on all participants and considered positive if a well-defined indirect immunofluorescence (IIF) pattern was identified.
Positive ANA-HEp-2 tests occurred in 12.9% of healthy participants. These involved low-to-moderate titers, and the most common ANA patterns were the nuclear fine speckled pattern (at low to moderate titer) in 45.8% of ANA-positive healthy participants and the nuclear dense fine speckled (DFS) pattern (frequently at high titer) in 33.1% of ANA-positive healthy individuals. None of the healthy patients had nuclear coarse speckled or nuclear homogeneous patterns.
In contrast, patients in the autoimmune disease comparison group had moderate-to-high titers of antibody and a distinct ANA profile characterized by the absence of the nuclear DFS pattern and the exclusive occurrence of nuclear coarse speckled, nuclear centromeric, nuclear homogeneous, and cytoplasmic DFS patterns. These patients also showed the nuclear fine speckled pattern, but at a higher titer than in healthy individuals.
At the end of a 4-year follow-up period, 72.5% of the ANA-positive individuals with the "healthy" pattern were still ANA-positive, but without any symptoms of autoimmune rheumatic disease.
Dr. Andrade told Medscape Medical News: "Our daily practice suggested that the ANA pattern might play a role in the interpretation of a positive ANA test. However, we were surprised by the extent with which this parameter may guide the clinical significance of a positive ANA test. Our results imply that certain ANA patterns, such as the nuclear homogeneous and the nuclear coarse speckled pattern, should direct a thorough clinical and laboratory investigation to unravel a systemic autoimmune disease, especially within the spectrum of systemic lupus erythematosus. Even if no abnormality is found in an initial screening, it may be wise to follow such patients for a while because they may be undergoing an incipient stage of the disease.
"In contrast, the finding of a nuclear [DFS] pattern, usually at high titer, most probably is not associated with systemic autoimmune diseases. Most of these individuals have no apparent disease and stay [that way] for years.
"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," Dr. Andrade said in a press statement.
Dr. Andrade said that that with careful training and updating, "the analyst in an ordinary clinical laboratory should be able to recognize the ANA patterns that are clinically relevant and those that are most probably observed in individuals with no apparent autoimmune disease."
Vai Chowdhary, MD, assistant professor of medicine at the Mayo Clinic's Division of Rheumatology, Rochester, Minnesota, was a bit more cautious. Dr. Chowdhary, who reviewed the paper for Medscape Medical News, said, "The interesting part in the paper is that high-titer ANA positivity was seen in some healthy individuals (up to 1:5120), and that the ANA titers cannot be used reliably to distinguish healthy individuals from patients with ARD. Their other conclusion that DFS may help distinguish healthy people from patients with ARD requires more data to be substantiated."
Specifically, Dr. Chowdhary said that previous research with large numbers of patients had found the DFS pattern in 37% of the participants, including those with a variety of nonrheumatic conditions.
"Based on this I would urge...caution while interpreting the DFS pattern as associated with healthy persons; more data, larger studies in heterogeneous populations, and different disease conditions (autoimmune as well as nonautoimmune) need to be studied before any firm conclusions can be drawn," Dr. Chowdhary said. "It would have also been useful to know how the DFS pattern sera reacts in the BioPlex [Bio-Rad] assay [vs the Bio-Rad and Bion assays used in the study], as more and more labs are shifting to detecting ANA by BioPlex."
Dr. Chowdhary added that although ANA by Hep-2 immunofluorescence can be performed in a typical clinical laboratory and is considered a gold standard for ANA testing, the method is plagued by interobserver variance, is labor intensive, and is suboptimal for laboratories requiring high-throughput technologies.
"Although this is a novel and thought-provoking article, several points need to be studied further," Dr. Chowdhary said. "The healthy control population consisted of blood donors, and none of them developed any autoimmune disease...after 3.9 years of follow-up. In the clinical setting, ANA is all too commonly tested for nonspecific symptoms of fatigue, joint pains, etc. Whether these patterns are seen in such a population and carry the same connotations as in study population needs to be studied further. My own bias is (based on previous published reports) that this pattern of staining may be seen in other autoimmune diseases as well, like multiple sclerosis or Hashimoto's thyroiditis. Therefore, larger populations and a variety of diseases need to be studied before this test finds application in clinical practice."
The study was supported by the São Paulo Research Foundation and the Brazilian Society of Rheumatology. Dr. Andrade and Dr. Chowdhary have disclosed no relevant financial relationships.
Arthritis Rheum. 2011;63:191-200. Abstract
poster:Phillipa
thread:976743
URL: http://www.dr-bob.org/babble/20101231/msgs/976743.html