New study finds infections common, tied to worse outcomes in AAV
Anti-PR3 positivity was linked to higher odds of infection
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In people with ANCA-associated vasculitis (AAV), infections were associated with higher odds of relapse and cardiovascular events, as well as a higher risk of death over time, according to a study in France.
Data also showed that testing positive for self-reactive antibodies against the proteinase 3 (PR3) protein was significantly associated with higher odds of infections, while methotrexate maintenance therapy appeared protective.
The results suggest that “anti-PR3 [antibody] positivity increases infection risk, whereas methotrexate appears protective,” the researchers wrote. “These findings highlight the need for close monitoring … and a continuous reassessment of therapeutic strategies in potentially vulnerable patients.”
The study, “Infectious complications of ANCA-associated vasculitis: Description and associated outcome,” was published in the European Journal of Internal Medicine.
Infections are a major concern in AAV
AAV is commonly associated with self-reactive antibodies that mistakenly target proteins, including PR3, found in neutrophils, a type of immune cell. This can overactivate the cells and lead to inflammation and damage in nearby small blood vessels, which can harm organs such as the kidneys and the lungs.
The immunosuppressive treatments commonly used for AAV can weaken the body’s response against infections. These treatments are, therefore, associated with an increased risk of infections, which “represent the leading cause of death” in people with AAV, the researchers wrote.
Here, a team of researchers in France looked at how often infections occur in AAV, how they affect long-term health, and what factors may increase infection risk. To do so, they retrospectively reviewed the medical records of 264 adults with AAV (48.5% women; median age 65), who were followed at a single French hospital.
All had either their first episode of AAV or an AAV relapse, meaning the disease became active again after a period of recovery, between January 2004 and December 2024. The median follow-up duration was 39 months, or a little over three years.
Nine patients were excluded from comparative analyses because they were followed for less than one month, resulting in a final group of 255 patients. An infection was counted if the patient needed to be hospitalized, closely monitored in a day hospital setting, or treated with anti-infective medications such as antibiotics, antivirals, or antifungals.
A total of 175 infectious events were reported in 112 patients (43.9%) during up to 20 years of follow-up. Infectious events were reported from days after AAV diagnosis to years later, with an average delay of about eight years after diagnosis.
Most infectious events (92%) required hospitalization, with a median hospital stay of eight days, and 15.4% required admission to the intensive care unit.
Most infections affected lungs and airways
Infectious events occurred most often in the lungs and airways (49.1%), followed by the urinary tract (21.3%), the skin (8.6%), and the digestive tract (7.4%). Most infectious events (75.3%) were caused by bacteria, especially Gram-negative bacilli, a group of bacteria that can cause serious disease in people with weakened immune systems. Other infections were caused by viruses (21.3%), most commonly the virus that causes COVID-19, or fungi (5.2%).
Initial statistical analyses showed that age older than 65, high blood pressure, diabetes, more active disease, and acute kidney injury were each significantly associated with infections. Use of intravenous (into-the-vein), high-dose corticosteroids, which are strong anti-inflammatory and immunosuppressive medications, was also significantly linked to infectious events.
Statistical analyses adjusted for potential influencing factors demonstrated that testing positive for anti-PR3 antibodies, one of the most common AAV-associated antibodies, was significantly associated with about two times higher odds of infection. In contrast, methotrexate maintenance therapy was significantly associated with lower odds of infection, although the researchers cautioned that few patients received methotrexate.
Adjusted statistical analyses also showed that infectious events were significantly linked to worse outcomes during follow-up. Patients with infections had nearly three times higher odds of AAV relapse and cardiovascular events, such as stroke, heart attack, cardiac arrest, or pulmonary edema. In survival analyses, infections were associated with more than double the risk of death over time.
“The risk of infection is not limited to the early phase of the disease but remains elevated over time and associated with detrimental outcome, emphasizing the need for [long-term] vigilance,” the researchers wrote.
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