Antibody testing results don’t offer simple black-or-white answers. A positive antinuclear antibody (ANA) test does not lead to an automatic diagnosis of autoimmune rheumatic disease, and multiple anti-neutrophil cytoplasmic antibody (ANCA) testing is not always clinically helpful or even appropriate.
“The diagnostic utility of ANCA testing is well established,” said Ulrich Specks, MD, Chair of Pulmonary and Critical Care Medicine at the Mayo Clinic. “The controversy is whether serial ANCA testing has clinical utility in managing patients. Recent publications and clinical trials point toward different roles for a variety of factors that can influence the clinical utility of serial ANCA testing. What this means is that the clinical utility of serial ANCA testing may not be the same in all patients.”
Dr. Specks will discuss the clinical significance of ANCA testing during the clinical symposium Update in Antibody Testing: Clinical Significance of Antinuclear and Anti-Neutrophil Cytoplasmic Antibodies from 11:00 am – 12:00 pm today. The most recent data suggest that patients with different clinical presentations may have different ANCA behaviors with different clinical implications.
“ANCA behavior and ANCA level changes may be different after different induction regimens and in different patients,” Dr. Specks said. “When different drugs are used to induce remission, what the ANCA levels do afterwards and how ANCA levels behave may be very different for different drugs. As a result, the clinical utility of following ANCA levels with serial testing may be different depending on those different factors.”
Serial ANCA testing is more helpful in patients with renal disease than it is in broader populations, he said. Obtaining multiple ANCA tests more likely benefits patients treated with rituximab compared with patients taking cyclophosphamide and subsequently azathioprine.
“As clinicians, our goal is to maintain the right balance between re-treating or prophylactically treating patients in a way that prevents relapse without causing too many side effects at the same time,” he said. “In order to achieve that balance between appropriate re-treatment and overtreatment for each individual patient, clinicians need to be aware of the various factors that affect the behavior of ANCA levels in different patients.”
Recent findings are changing concepts about the clinical utility of ANA testing. It has long been recognized that a substantial proportion of positive ANA results are not associated with systemic autoimmune rheumatic diseases.
“When one does an immunofluorescence ANA test, the results show a quantitative titer and a visual pattern that is based on how antibodies are binding,” said Mark Wener, MD, Director of Clinical Laboratories at the University of Washington Medical Center and Professor of Laboratory Medicine and Rheumatology. “We are beginning to realize that one of these patterns, a dense fine speckled pattern, could be broken out and reported separately. Patients who exhibit this specific pattern are at no greater risk for autoimmune rheumatic disease than the general population even though they have a positive ANA.”
Patients with fibromyalgia and other nonspecific complaints that could indicate rheumatic disease are often referred for ANA testing. Few laboratories that conduct ANA testing report findings of a dense fine speckled pattern, and even fewer clinicians are aware of its clinical significance, Dr. Wener said.
But reporting this specific pattern could make a significant difference in clinical practice. Finding this dense fine speckled pattern could reassure patients that they are likely not developing an autoimmune disease. It would also help stratify these patients as low risk and obviate the need for additional autoimmune testing, saving time, money, and clinical resources.
“This pattern simply does not have the same clinical significance as other positive ANAs,” Dr. Wener said. “We should be looking for this pattern and reporting it because it has very positive implications for patients.”