1 in 10 ANCA-positive people with lung disease develop AAV
Risk factors include being positive for ANCAs against MPO, rheumatoid factor
About 1 in 10 people with idiopathic interstitial pneumonia (IIP), a condition marked by lung scarring of an unknown cause, who test positive for antineutrophil cytoplasmic antibodies, or ANCAs, eventually develop ANCA-associated vasculitis (AAV), a study shows.
These patients’ risk factors for AAV include testing positive for ANCAs against myeloperoxidase (MPO), one of the two common targets of AAV-driving ANCAs, or for rheumatoid factor, a self-reactive antibody associated with rheumatoid arthritis, another autoimmune disease.
The study “emphasizes the importance of careful monitoring in patients with high-risk antibody profiles, even if the complete features of AAV are not present at IIP diagnosis,” the researchers wrote in “Progression to ANCA-associated vasculitis in patients with idiopathic interstitial pneumonia and positive ANCA,” which was published in Seminars in Arthritis and Rheumatism.
ILD is a group of inflammatory disorders that feature scarring around alveoli, the tiny air sacs responsible for the exchange of gases in the lungs. Symptoms include shortness of breath, coughing up blood, and chest pain.
“When the cause of ILD remains unidentified despite aggressive investigations, it is classified as idiopathic interstitial pneumonia (IIP),” the researchers wrote.
ILD can be a manifestation of organ involvement in AAV, a group of rare autoimmune conditions marked by inflammation and damage to small blood vessels that can affect several organs, including the lungs and kidneys. The presence of ILD in AAV is particularly common among those with ANCAs against MPO.
In most AAV cases, self-reactive antibodies, called ANCAs, drive the damaging inflammation. These abnormal antibodies typically target one of two proteins, MPO or proteinase 3.
However, “not all patients with positive ANCA results at the time of diagnosis of ILD present with the complete features of AAV,” the researchers wrote. “Previous studies have reported a varied timing of AAV occurrence, presenting before, at the same time, or after ILD diagnosis in patients with positive ANCA results, affecting 8-100% of these patients.”
Risk factors for AAV with lung disease
Still, few studies have investigated risk factors for developing AAV in the future among people diagnosed with IIP and positive for ANCAs, leading a research team in South Korea to retrospectively analyze data from 154 adults who had positive ANCA test results in the absence of AAV at the time of their IIP diagnosis. The patients were a median age of 68 and most were men (63%). At IIP diagnosis, none showed kidney involvement, a common AAV manifestation, as assessed using the Birmingham Vasculitis Activity Score. Available data on the type of ANCA showed most were positive for antibodies targeting MPO.
IIP treatment most commonly included corticosteroids (57.8%), a type of anti-inflammatory medication, followed by anti-scarring agents (44.8%).
During a median follow-up of 29.5 months, or nearly 2.5 years, 16 patients (10.4%) developed AAV; nearly all (93.8%) within three years of their IIP diagnosis. All but four showed kidney involvement, as evidenced by kidney inflammation on biopsy.
At IIP diagnosis, the eventual AAV and non-AAV groups didn’t significantly differ by sex, age, smoking status, urine test results, CT chest scan findings, or type of medications to treat IIP. Those who did develop AAV had significantly better lung function, however.
Also, anti-MPO ANCAs were detected in all eventual AAV patients, but only in about half (48.8%) of those who didn’t develop the disease. Significantly more AAV patients tested positive for rheumatoid factor than non-AAV patients (62.5% vs. 29.2%).
Testing positive for anti-MPO antibodies was significantly associated with a 38 times increased likelihood of developing AAV among IIP patients who tested positive for ANCAs, statistical analyses revealed. Testing positive for rheumatoid factor was significantly linked to a four times higher chance of AAV. Testing positive for either antibody was significantly linked to a higher incidence of AAV, further analysis confirmed.
Thirty patients (19.5%) died during follow-up. Identified causes of death included infection, cancer, or sudden ILD worsening. The rates or causes of death didn’t significantly differ between AAV and non-AAV groups.
This study “underscores the importance of close monitoring and observation in patients with high-risk antibody profiles for the potential development of AAV, even in cases where AAV was not diagnosed at the time of the initial diagnosis of IIP,” the researchers said.
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