Blood levels of ANCAs can help identify AAV and its severity: Study
Higher ANCA levels found to be tied to greater lung, kidney involvement
Blood levels of ANCAs — the disease-causing antibodies that give ANCA-associated vasculitis (AAV) its name — can be used to help distinguish AAV from other conditions in which ANCAs might also be present, a study showed.
Higher levels of the antibodies at diagnosis also were significantly tied to greater AAV disease severity — including lung or kidney involvement. They were not, however, linked to a particular prognosis.
The study, “ANCA detection with solid phase chemiluminescence assay: diagnostic and severity association in vasculitis,” was published in Immunologic Research.
But levels of ANCAs not linked to prognosis
AAV encompasses a group of autoimmune disorders characterized by inflammation and damage (vasculitis) to small- and medium-sized blood vessels. This is caused by ANCAs, a family of self-reactive antibodies that bind to enzymes in immune cells called neutrophils, ultimately leading to the cells’ overactivation.
The main types of ANCAs are those targeting the myeloperoxidase (MPO) and proteinase 3 (PR3) enzymes.
While looking for these antibodies can help diagnose AAV, their presence alone is not enough to reach a diagnosis. That’s because ANCAs may sometimes, albeit less frequently, be found in people with other diseases. Moreover, some people may have AAV, but test negative for the known antibody types.
Measuring these antibodies also is thought to be a way of helping to monitor AAV, as their levels “may correlate to severity, prognosis, and recurrence of the disease,” the researchers wrote. However, how exactly meeting cut-off levels of ANCAs can predict disease features was still not completely worked out.
To learn more about the ability for blood ANCA levels to identify AAV patients and predict its course, a team of researchers now retrospectively analyzed patient data. The data were culled from individuals who were positive for MPO- or PR3-ANCAs in a blood test at the time of their diagnosis, at a clinic in northern Spain.
A total of 101 patients, with a mean age of 64.3, were positive for anti-MPO antibodies. In all, 77 patients were considered to have some form of vasculitis, or blood vessel inflammation, with most (85.7%) having a form of AAV.
The most common form of AAV was microscopic polyangiitis, or MPA, found in 34 patients. This type of AAV usually is linked to anti-MPO ANCAs. The type of vasculitis was not completely classified in 11 patients.
The 24 people without vasculitis had a range of other conditions, including infections, tumors, and autoimmune diseases.
Results suggest cut-off values for enzyme levels
Higher MPO-ANCA levels were significantly associated with a vasculitis diagnosis and with greater disease severity. The scientists recommended that the best MPO-ANCA cut-off level for predicting a person had vasculitis was 41.5 international units per milliliter (IU/mL) or higher.
This value was chosen based on a balance between its sensitivity — the percentage of vasculitis cases being correctly identified — and specificity, or the percentage of unaffected cases being correctly ruled out. Based on this, the overall performance of the cut-off value was about 80.8%.
To specifically predict an MPA diagnosis, the identified cut-off value was 36.5 IU/mL, with a 64.4% accuracy.
Another 54 people, with a mean age of 55.7 years, were positive for anti-PR3 antibodies. This included 44 patients with a form of vasculitis, most commonly AAV (84.1%), followed by drug-induced vasculitis (11.4%). Of the two remaining patients, one had large vessel vasculitis and the other had unclassified vasculitis.
The most common type of AAV was granulomatosis with polyangiitis, known as GPA, seen in 33 patients. This is a form that’s typically associated with PR3-ANCAs.
Among the 10 patients with MPO-ANCAs and no vasculitis, an inflammatory condition of the large intestine called ulcerative colitis was the most common (60%).
Again, higher levels of anti-PR3 antibodies were significantly associated with a vasculitis diagnosis and worse severity.
Analyses indicated that at a cut-off value of 20.5 IU/mL could discriminate between patients with and without vasculitis with an accuracy of 73.2%.
Altogether, while “ANCA can be positive in a number of conditions that mimic AAV,” the researchers wrote, the levels of the antibodies can be used to help distinguish the right diagnosis.
Some individuals experience continuous disease relapses, so it is crucial to continue looking for indicators that can signal a progression of the condition so that the dose of the treatment can be adjusted properly.
ANCA levels at diagnosis also were shown to be able to differentiate AAV patients with kidney or lung involvement — who are generally considered to have greater disease severity — from those who did not.
Levels of anti-MPO antibodies were significantly higher in patients with these complications, with a recommended cut-off value to distinguish them of 60 IU/mL. Likewise, PR3-ANCA levels were significantly higher in patients with this organ involvement, with a recommended cut-off value of 41.5 IU/mL.
In turn, levels of either type of ANCA were not associated with disease prognosis, including need for dialysis, kidney or lung transplant, or death.
“The ANCA [level] at diagnosis can therefore be used to estimate the disease severity but not the course of the disease,” the researchers wrote.
“Some individuals experience continuous disease relapses, so it is crucial to continue looking for indicators that can signal a progression of the condition so that the dose of the treatment can be adjusted properly,” they added.
Study limitations included a lack of definitive AAV diagnosis for some patients as well as recent diagnoses and short-term follow-up for some patients.
“It would be interesting to increase the number of patients studied and analyze a more detailed follow-up,” the researchers wrote.