A significant proportion of patients who test positive for antibodies associated with ANCA-associated vasculitis (AAV) do not have the disease, according to a study. Its findings also suggested that a higher threshold of these antibodies could be used to improve diagnosis of the condition, since people with higher levels have a greater likelihood of having AAV.
The study, “Clinical significance of positive anti‐neutrophil cytoplasmic antibodies without evidence of anti‐neutrophil cytoplasmic antibodies‐associated vasculitis,” was published in the International Journal of Rheumatic Diseases.
Testing for the presence of anti-neutrophil cytoplasmic antibodies (ANCA) is widely used in the diagnosis of AAV. Two common methods are used: one detects if ANCAs are located around the nucleus (P-ANCA) or scattered in the cytoplasm (C-ANCA), and the another determines with a higher specificity if these antibodies are against the proteinase 3 (PR3-ANCA) or the myeloperoxidase (MPO-ANCA) proteins — the two most common targets of ANCA antibodies. Anti-PR3 are usually associated with C-ANCA, and anti-MPO antibodies are linked with P-ANCA.
While more recent methods have improved the detection of ANCA antibodies, some patients testing positive for the C-ANCA/PR3 antibody have been diagnosed with disorders other than AAV. As well, studies are scarce on the clinical meaning of testing positive for P-ANCA/MPO in patients with vasculitis.
The team from Israel investigated the clinical spectrum of having the anti-PR3 or MPO antibodies in patients without AAV. They also evaluated the proportion of patients without evidence of AAV among all those with PR3 or MPO antibodies.
The study included 113 patients who tested positive for ANCA antibodies between 2007 and 2016. All patients were followed up for at least one year to ensure that the correct diagnosis had been made.
In total, 60.2% of these patients had no evidence of AAV, with 68 patients positive for C-ANCA/PR3 (59% of them did not receive an AAV diagnosis), and 45 positive for P‐ANCA/MPO antibodies (62% did not receive an AAV diagnosis).
Antibody detection using both testing methods had a positive predictive value — the probability that a positive result corresponds to having the disease — of 40%. Researchers found that higher levels of ANCA antibodies were more common in people with AAV than in those without the condition.
The main indications for testing for the presence of these antibodies among patients with AAV were lung disease (40%), renal failure (40%), and sinusitis (9%). Among those without the condition, the main indications were lung disease (22%), renal failure (16%), and constitutional syndrome (9%), which may include fatigue, anorexia, and involuntary weight loss.
Patients without AAV, but positive for C‐ANCA/PR3 antibodies, were most frequently diagnosed with infectious diseases (20%) and inflammatory bowel disease (12.5%). Those with P‐ANCA/MPO antibodies were more commonly diagnosed with connective tissue disease (10.7%), an indication not found in patients with C‐ANCA/PR3. Other diagnosed conditions included autoimmune diseases, sudden hearing loss, and lymphoma.
“These findings underscore the fact that ANCA test results should be interpreted with caution, since positive results are found in heterogeneous non‐vasculitic conditions,” the researchers said.
The data further revealed that approximately half of the patients not diagnosed with AAV had had an indication for ordering ANCA antibody tests. “Clinical consideration should be employed when ordering ANCA tests,” the scientists said, “in order to decrease unnecessary costly tests and false positive results.”
“We have demonstrated that a significant proportion of patients with a positive C-ANCA/PR3 or P‐ANCA/MP do not have evidence of ANCA‐associated vasculitis,” they concluded. As a result, higher threshold of ANCA titers may be required to improve specificity.”