GPA Management Should Not Be Based on ANCA Levels Alone, Study Suggests

In granulomatosis with polyangiits (GPA) patients, the levels of anti-neutrophil cytoplasmic autoantibodies (ANCAs) — the autoantibodies associated with the condition — appear to correlate with worse disease activity, a study has found.

However, ANCAs remain high in many patients who enter clinical remission, suggesting that disease management cannot proceed based on ANCA levels alone, researchers said.

The study, “Antineutrophil cytoplasmic antibodies and their relationship with disease activity and presence of staphylococcal superantigens in nasal swabs in patients having granulomatosis with polyangiitis: results of a study involving 115 patients from a single center,” was published in the journal Clinical Rheumatology.

The blood vessel damage that characterizes ANCA-associated vasculitis is mostly caused by self-antibodies called ANCAs. These attack a type of white blood cell called neutrophils, making them attach and produce substances that are toxic to blood vessels.

While most GPA patients (95%) are positive for ANCAs at diagnosis, researchers are still not sure whether the levels of these autoantibodies are useful for monitoring disease activity.

Also, some investigators believe that microbial components, like those of Staphylococcus aureus, may play a part in vasculitis development by inducing the formation of more ANCAs. In fact, 60 to 70% of GPA patients carry S. aureus chronically in their nasal mucosa, compared to only 20 to 30% of healthy people.

Aiming to address these questions, researchers at the National Tuberculosis and Lung Diseases Research Institute in Poland examined 115 GPA patients, admitted to hospitals from 2009 and 2016, and examined whether ANCA levels correlated with disease activity and whether ANCA levels rose in the presence of S. aureus proteins.

During the study period, patients reported a total of 362 hospital visits. On each visit, disease activity was measured using the Birmingham Vasculitis Activity Score (BVAS), and blood samples and nasal swabs were collected.

Only one-third (32.6%) of hospital visits were due to active disease, either in newly diagnosed patients, in those having a relapse, or in patients experiencing disease progression. The remaining patients had no signs attributable to active disease and had normal indicators of inflammation.

ANCAs were detected in 59.4% of hospital visits, but they weren’t exclusive to visits associated with active disease. In fact, while a great proportion of patients (70.3%) with active disease were positive for these antibodies, ANCAs were still detected in more than half of non-active cases (54.1%), which included patients in remission.

Researchers found a significant correlation between the presence of ANCAs and active GPA, and the higher the ANCA levels, the more severe the disease was. They also were able — for the first time — to determine a cut-off value (138 Ru/ml) distinguishing patients with active and non-active GPA.

This value identified patients with active disease with a high specificity (84.4%; the proportion of true negatives that are correctly identified as such), but with a low sensitivity (37.3%; the proportion of patients with active disease that have a positive result in the test). The researchers attribute this low sensitivity to the 54.1% of patients in whom “ANCAs persist despite effective treatment and clinical remission of disease.”

“Our results confirmed the correlation between ANCA presence and GPA activity: higher ANCA levels are associated with more severe GPA,” they wrote.

Bacterial antigens (proteins able to elicit an immune response) were found in 126 samples from 56 patients. The most common antigen, staphylococcal enterotoxin type A (SEA), was found in 60% of the cases, while the least frequent (6.3%) was staphylococcal enterotoxin type B (SEB).

Researchers found no correlation between presence of S. aureus antigens in nasal swabs and ANCA levels in the overall population. However, patients with the SEB antigen had significantly higher levels of ANCAs.

“The suspected clinical correlation between ANCA formation and [S. aureus antigens] presence in nasal swabs is not obvious and requires further investigations,” researchers wrote.

Overall, these findings suggest that while “monitoring ANCA levels as a marker of disease activity may be clinically relevant, GPA management cannot proceed on the basis of ANCA levels alone,” the study concluded.