Urine, blood biomarkers may help track AAV activity: Study

Researchers suggest more studies on nonivasive ways to monitor disease

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Biomarkers measured in blood or urine may help track disease activity and organ damage in people with ANCA-associated vasculitis (AAV), according to a systematic review study.

AAV is an autoimmune disorder in which self-reactive antibodies called anti-neutrophil cytoplasmic antibodies (ANCAs) attack the body’s own neutrophils — a type of immune cell — triggering blood vessel inflammation and potentially leading to organ damage.

A key part of managing AAV is detecting when the disease is active, especially after initial treatments have driven the disorder into remission. To aid in tracking disease activity and organ damage, clinicians often rely on repeated biopsies of the kidneys or other affected organs.

These invasive procedures may come with complications, so scientists are working to identify noninvasive biomarkers — such as those found in blood or urine — that can provide information about disease activity.

To that end, a team of scientists in Canada and Belgium conducted what they called “the first contemporary systematic review synthesizing the value of non-invasive biomarkers of AAV-related disease activity and organ damage.” The study, “Non-invasive biomarkers of disease activity and organ damage in ANCA-associated vasculitis: a systematic review,” was published in RMD Open Rheumatic and Musculoskeletal Diseases.

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‘Many unmet needs’ in research on urine, blood biomarkers

The researchers said they identified “many unmet needs,” noting that there were few studies involving the rarest type of AAV or childhood-onset AAV.

“Further validation of the candidate biomarkers is warranted in large prospective studies to bridge the existing knowledge gaps and apply precision [medicine to AAV],” the team wrote.

The analysis involved 22 studies covering a total of 2,362 people with AAV. A total of 66 patients were identified as having eosinophilic granulomatosis with polyangiitis (EGPA), the rarest AAV type, and “few studies included juvenile patients,” the researchers noted.

More than half the patients had ANCAs against the myeloperoxidase (MPO) enzyme, one of the two most common targets of these antibodies, in their blood. The results indicated that reappearance of anti-MPO ANCAs in the blood after becoming undetectable during AAV remission is a strong sign that the disease is once again active.

According to the researchers, more work is needed to fully understand the association between ANCAs and disease activity and to assess if the same holds true for other types of ANCAs.

“Although the diagnostic role of ANCA is well defined, the value of ANCA levels in the assessment of AAV disease activity remains less clear,” the scientists wrote, adding that the findings at least warrant “caution in the follow-up and management of patients with AAV in clinical remission with a reappearing or rising ANCA level.”

Evidence also suggested that higher levels of certain monocytes, a type of immune cell, and of inflammatory molecules, like CXCL13, IL-8, and IL-15, are associated with active AAV.

Other blood markers of disease activity included scores suggesting high activity of genes related to neutrophils and signs of activation in the complement cascade, a part of the immune system whose overactivity contributes to inflammation in AAV.

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Urinary biomarkers match kidney biopsies, predict outcomes

Urine biomarkers found useful in assessing kidney health

Biomarkers in urine can be used to indirectly assess kidney health, the researchers said. High levels of the sCD163 protein in urine appear to be a strong marker of AAV-related glomerulonephritis (GN), or inflammation in the kidneys’ filtering units.

“Urinary sCD163 represented the single most reliable biomarker for active ANCA-associated GN,” the researchers wrote, adding that the protein has been identified as a potential biomarker of other autoimmune kidney diseases.

“Future research should assess how this marker can be incorporated in our clinical decision-making,” they wrote.

The ultimate goal is to enhance precision [medicine] by obtaining a more reliable assessment of disease extent, severity and prognosis at presentation precluding the need for serial biopsies.

Some complement proteins, certain immune cell subsets, and mitochondrial DNA — a type of DNA stored in cells’ energy-making mitochondria — also tended to be elevated in urine of AAV patients with active kidney disease and poor kidney function.

In both blood and urine samples, higher levels of the endotrophin protein were generally associated with poorer kidney function.

The researchers also said blood high levels of the inflammatory protein CCL2 appear to be a marker of interstitial lung disease (ILD) in AAV. ILD is a general term referring to disorders where there’s excess scarring in the lungs, making it hard to breathe.

The study found “several non-invasive biomarkers may be beneficial in the assessment of AAV-related disease activity and/or organ damage,” the researchers wrote, adding that “further validation … is warranted before routine clinical implementation,” such as use in childhood-onset AAV and EGPA patients.

“It seems unlikely that a single biomarker will be able to provide sufficient discriminative power to impact our clinical decision-making; multiplexed biomarker panels should therefore be developed and validated in patients with AAV,” the researchers wrote.

“The ultimate goal is to enhance precision [medicine] by obtaining a more reliable assessment of disease extent, severity and prognosis at presentation precluding the need for serial biopsies,” they concluded.