ANCA antibodies against both PR3, MPO result in hybrid AAV features

Double-positive patients show kidney involvement, lower remission rates

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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A red-colored bloom amidst a field of white colored blooms illustrate rare disease.

People with ANCA-associated vasculitis (AAV) who are positive for antibodies against both myeloperoxidase (MPO) and proteinase 3 (PR3) show a combination of clinical characteristics from patients with each antibody type, according to a recent study in China.

While double-positive patients are generally more similar to those with MPO-ANCAs, particularly regarding kidney involvement, these patients shared the lower remission rates and higher disease relapses observed in those carrying PR3-ANCAs alone.

“Despite no significant differences in the death rate when comparing … double-positive AAV with MPO-AAV or PR3-AAV, there was no denying that the overall patient survival of idiopathic double-positive AAV was poor,” the researchers wrote in “Clinical features and prognosis of ANCA-associated vasculitis patients who were double-seropositive for myeloperoxidase-ANCA and proteinase 3-ANCA,” which was published in  Clinical and Experimental Medicine.

The researchers said these “patients should be very carefully monitored.”

AAV is a group of autoimmune diseases where small blood vessels become inflamed and damaged due to anti-neutrophil cytoplasmic antibodies (ANCAs), that is, self-reactive antibodies that bind to and activate immune cells called neutrophils.

ANCAs typically target either the PR3 or the MPO proteins and each antibody type results in distinct disease manifestations. Patients may have antibodies that target the two proteins in rare cases, but it’s not fully known how the disease manifests in these patients, leading researchers to examine the electronic medical records from 340 patients followed at a medical center in China between 2010 and 2020.

“Whether AAV patients who were double positive for PR3-ANCA and MPO-ANCA were distinguishable from single positivity AAV for PR3-ANCA or MPO-ANCA remains elusive,” the researchers wrote.

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Characteristics of both antibody types

The participants were mainly men (53.2%) and had a mean age of 58.4 when they were diagnosed. Most (84.1%) had MPO-ANCA antibodies, while 10.9% had PR3-ANCA antibodies and 5% had both types.

In general, double-positive AAV patients had several disease characteristics that were similar to those with anti-MPO antibodies, such as an older age at disease onset and a higher proportion with microscopic polyangiitis (MPA), the most common type of AAV. In the PR3-ANCA group, patients were younger and most had the granulomatosis with polyangiitis (GPA) type.

The degree of anemia, or low levels of the oxygen-carrying protein hemoglobin, in double-positive patients was also comparable to that of MPO-AAV patients and more severe in both groups than in the PR3-AAV patients.

Both double-positive and MPO-AAV patients had lower overall disease activity, as measured with the Birmingham Vasculitis Activity Score, and fewer symptoms involving the ear, nose, and throat than the PR3-AAV group. But groups had more severe kidney damage and more often progressed to end-stage kidney disease than the PR3-AAV patients.

Still, double-positive patients had the worst remission rates across the three groups (58.8% vs. 83.2% in MPO-AAV and 78.4% in PR3-AAV), and their relapse rate was high, similar to what was seen in the PR3-AAV group (40% vs. 44.8% for PR3-AAV vs. 23.5% for MPO-AAV).

These patients also had the lowest number of white blood cells and platelets compared with the other two groups. But they had the lowest death rate, comparable to those with PR3-AAV (11.8% vs. 13.5%). Those with MPO-AAV had the highest death rate (31.5%), though no significant differences were seen regarding long-term survival.

The study shows that “double-positive AAV is a rare clinical entity with hybrid features of MPO-AAV and PR3-AAV. MPO-AAV is the ‘dominant’ phenotype,” wrote the researchers, who noted that along with “the high risk of relapse like PR3-AAV … double-positive AAV patients also experience unfavorable long-term renal prognoses like MPO-AAV.”