Researchers Call for Combined Tests to Correctly Diagnose GPA, a Form of Vasculitis

More than one detection technique may be necessary to confirm the diagnosis of granulomatosis with polyangiitis (GPA), a type of vasculitis, researchers found.

The study found that samples that had been previously considered negative for GPA when tested for the presence of ANCA proteins were actually positive when researchers used different tests.

Findings from the study, “A novel strategy with combined assays for detection of antineutrophil cytoplasmic antibody (ANCA) in clinically ANCA-negative granulomatosis with polyangiitis patients,” were published in the journal Auris Nasus Larynx.

GPA is a type of autoimmune disease caused by the body’s own ANCA antibodies. ANCAs are autoantibodies that attack the inside of neutrophils, a type of white blood cell. When ANCAs attack the neutrophils, white blood cells damage the walls of small blood vessels (vasculitis) in different tissues and organs of the body.

“Positive detection of ANCA is important for diagnosis and management of the disease,” researchers wrote.

To investigate whether the diagnosis of GPA could be improved with additional tests, researchers used 29 blood samples obtained from patients with GPA in the upper airway and tested them for the presence of ANCA proteins involved in vasculitis, such as PR3-ANCAs and MPO-ANCAs, the most common subsets of ANCA.

They also looked for the presence of less common ANCAs, such as those targeting elastase, lactoferrin, and lysozyme. These also target components of the neutrophils, but due to their lower abundance, were called minor ANCAs.

Of the 29 patients, 12 were positive for PR3- or MPO-ANCAs, whereas 17 patients were negative for both proteins. However, additional tests showed that four of the 17 samples first deemed negative for PR3- or MPO-ANCAs were actually positive. Three other samples were positive for minor ANCAs.

Indeed, samples from eight patients that had been considered negative were actually ANCA-positive in other tests. The use of different detection techniques significantly improved the ANCA diagnostic rate from 41.4 percent (12 of 29 patients) to 69 percent (20 of 29 patients).

“In conclusion, clinically ANCA-negative samples should be confirmed using other … detection techniques for antibodies against particular target antigens, mainly PR3 and MPO, particularly when vasculitis is clinically suspected,” researchers wrote. “Minor ANCAs should also be tested when PR3- and MPO-ANCA are negative. Moreover, development of novel detection technologies is essential for improvements in the methods for ANCA detection.”