Increase in ANCA Antibodies Linked to AAV Relapse Within 6–12 Months

Researchers question if at-risk patients should be treated pre-emptively

Somi Igbene, PhD avatar

by Somi Igbene, PhD |

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An increase in ANCA antibodies may predict a relapse within six to 12 months in people with ANCA-associated vasculitis (AAV), according to a new study.

The link between an antibody rise and AAV relapse was found to be significant in patients with myeloperoxidase (MPO)-ANCAs, or antibodies against the MPO protein that is often targeted by ANCAs.

“These results provide further support to monitor patients with an ANCA rise more closely and raise the question if patients should be treated pre-emptively to prevent a potential disease relapse with subsequent organ damage,” the researchers wrote.

The team noted, however, that more than 50% of individuals with an ANCA rise do not have a relapse during that six-month period — “and these patients risk complications of overtreatment such as infections.”

The study, “Do relapses follow ANCA rises? A systematic review and meta-analysis on the value of serial ANCA level evaluation,” was published in the journal Frontiers in Medicine.

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Antibody levels help diagnose, monitor AAV

AAV is a condition characterized by inflammation and damage to blood vessels. AAV occurs when antibodies called anti-neutrophil cytoplasmic autoantibodies, or ANCAs, target and attack a type of immune cells known as neutrophils. ANCAs mainly target proteinase 3 (PR3) and MPO proteins found within neutrophils.

Optimal treatment of AAV is challenging because the disease course is unpredictable. Although some patients achieve stable remission after therapy, others experience relapses that lead to severe organ damage.

A patient’s levels of ANCA antibodies are used to diagnose and monitor AAV. However, differences in the techniques used to measure these levels make it difficult to interpret what ANCA increases mean when they are assessed during remission. Specifically, it is unclear whether ANCA antibody increases predict relapses.

To learn more, a team of scientists at the University of Amsterdam, in the Netherlands, reviewed research studies published from 1993 to 2021. Their goal was to determine whether increases in ANCA levels, measured with a specific technique, predict AAV relapses immediately, or within six and 12 months after they rise.

The scientists searched the MEDLINE, EMBASE, and COCHRANE databases for studies assessing the ability of ANCA levels to predict relapse and monitor AAV disease activity. Of 806 studies, 20 were selected to be included in the final analysis.

ANCA antibodies were present immediately after relapses in patients who previously achieved remission. While increases in ANCA antibodies did not predict immediate relapses, they were linked to a significantly higher risk of relapse within six and 12 months, especially in patients with MPO-ANCAs.

“Although an AAV relapse is associated with positive ANCA, rises in ANCA level are not indicative of a concurrent disease relapse. However, ANCA increases do associate significantly with higher odds of having a disease relapse within the first 6 and 12 months after measurement. This association is strongest in MPO-ANCA positive patients and loses significance in PR3-ANCA positive patients,” the researchers wrote.

Overall, this study demonstrates the clinical value of monitoring ANCA levels in patients who are in remission, according to the team. The researchers also suggested possibly initiating treatment in those whose ANCA levels rise to avoid organ damage.

“Our meta-analysis confirms that in previously ANCA-positive patients, the ANCA test is often positive upon clinical suspicion of a disease relapse and increasing ANCA may be helpful to identify patients that are more at risk of encountering disease relapses in the upcoming six or 12 months, and for whom pre-emptive treatment could be a realistic possibility,” they concluded.