In AAV, testing positive for C-ANCA raises risk of lung bleeding 5 times
Study also found 4 times greater risk of lung disease for those with P-ANCA
People with ANCA-associated vasculitis (AAV) who test positive for a staining pattern of self-reactive antibodies called cytoplasmic ANCA (C-ANCAs) are nearly five times more likely to have bleeding into the lungs’ air sacs, known as alveolar hemorrhage, a study found.
C-ANCA is marked by the presence of ANCAs — the self-reactive antibodies that drive most AAV cases — in the cell’s cytoplasm. That’s the jelly-like substance that fills the inside of a cell, except its nucleus, which is where all genetic information is stored.
A different risk was found, meanwhile, for patients with ANCAs detected around the cell’s nucleus. This condition, known as perinuclear ANCA, or P-ANCA, was linked to a four times higher risk of interstitial lung disease, or ILD, a group of conditions marked by inflammation and scarring (fibrosis) between the lung’s air sacs.
According to the researchers, “[alveolar hemorrhage] was found to be higher in … patients with C-ANCA positivity.” Meanwhile, “it was shown that P-ANCA positivity predicted ILD,” the team wrote.
The study, “A closer look to the lung involvement in ANCA-associated vasculitis: alveolar haemorrhage and interstitial lung disease,” was published in the journal Clinical and Experimental Medicine by a research team in Turkey.
AAV is a group of autoimmune diseases characterized by inflammation and damage to small blood vessels. Most cases of AAV are caused by self-reactive antibodies called ANCAs that bind to neutrophils, a type of immune cell, and trigger an immune reaction against cells lining blood vessels.
P-ANCA more common in those with MPA, C-ANCA in people with GPA
In clinical practice, ANCAs can be detected either by their target — usually the proteinase 3 (PR3) or myeloperoxidase (MPO) enzymes — or by their staining pattern on lab tests, which can be perinuclear or cytoplasmic. Most P-ANCAs patterns are due to ANCAs targeting MPO, while C-ANCAs results are typically associated with anti-PR3 ANCAs.
P-ANCA is more frequently detected in people with microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis, two types of AAV, while C-ANCA is typically detected in individuals with another AAV type called GPA, for granulomatosis with polyangiitis.
AAV symptoms vary widely depending on the affected tissues, but many patients experience problems with their lungs and kidneys. Lung issues may include ILD and alveolar hemorrhage.
To know more about the factors that may predict these two issues in people with AAV, a trio of researchers retrospectively analyzed clinical and laboratory data from 83 patients followed at the University of Health Sciences in Ankara between 2016 and 2024.
The participants had a mean age of 47.6, and slightly more than half were men. The majority — about two-thirds of patients — had C-ANCA, while about one-quarter had P-ANCA. A total of 6% had no detectable ANCAs. All were followed for a mean of 4.8 years.
Lung involvement was present in most participants (65%) at the time of diagnosis. This was followed by kidney involvement, seen in 35%. During follow-up, these proportions increased to 76% and 64%, respectively.
“All patients received glucocorticoid treatment, and other immunosuppressive treatments were given alone or in combination,” the researchers noted.
Researchers call for more study into lung bleeding, lung disease in AAV
A significantly greater proportion of participants with C-ANCA had lung involvement (78.6% vs. 54.5%) and kidney involvement (71.4% vs. 40.9%) than those with P-ANCA. Ear, nose, and throat involvement likewise affected a larger proportion of patients with C-ANCA than P-ANCA (37.5% vs. 13.6%).
Among lung issues, the C-ANCA group had a significantly higher rate of alveolar hemorrhage (37.5% vs. 13.6%) and a lower rate of ILD (10.7% vs. 31.8%) than the P-ANCA group.
Usual interstitial pneumonia (UIP), the most common ILD pattern in AAV, was also significantly more common in participants with P-ANCAs (22.7% vs. 3.6%).
After adjusting for patients’ age and sex, C-ANCA was significantly linked to a 4.8 times higher chance of having alveolar hemorrhage, while P-ANCA was significantly associated with a 4.3 times higher likelihood of having ILD, according to the researchers.
Among the five participants without ANCAs, four had GPA, and one had MPA. Regarding lung involvement, two had ILD and one had alveolar hemorrhage.
Overall, these findings indicate that alveolar hemorrhage was more common among “patients with C-ANCA positivity, while P-ANCA positivity was shown to predict ILD involvement in AAV patients,” the researchers wrote.
Larger studies, following patients over time, “are needed to better define the prevalence and evolution of ILD and [alveolar hemorrhage] in AAV, its clinical [profile] and possibly a better therapeutic approach,” the team concluded.
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