Japanese Researchers Identify Nine Biomarkers of ANCA-associated Vasculitis

The protein TIMP1 is a promising biomarker of ANCA-associated vasculitis activity, according to a Japanese study that also identified markers of the disease’s damage to the kidneys and lungs.

Altogether, the researchers identified nine proteins that could be suitable biomarkers.

Researchers published their work in the journal Arthritis Research & Therapy. It is titled “Targeted proteomics reveals promising biomarkers of disease activity and organ involvement in antineutrophil cytoplasmic antibody-associated vasculitis.”

While ANCA antibodies play a key role in the development of the disease, levels of ANCA are not sensitive or specific enough to diagnose the disease — whose acronym is AAV — or track its progression. ANCA stands for antineutrophil cytoplasmic antibodies.

Other proteins that may play a role in the disease, such as CRP, or C-reactive protein, are also not specific or sensitive enough to be used as biomarkers, researchers said. So scientists have needed to find markers that could better monitor the disease and help doctors manage it.

In addition to tracking the disease’s progression, biomarkers are needed to determine which organs the disease is damaging — since it can affect a lot of organs. Previous studies have identified possible biomarkers, but scientists say none is capable of diagnosing the disease accurately or identifying which organs it is affecting.

Japanese researchers decided to use an analytical technique called selected reaction monitoring mass spectrometry to try to identify useful biomarkers. It can detect particular molecules in a complex protein sample.

The team used the approach to analyze blood serum samples of both patients with an active disease and patients whose disease was in remission. The analysis covered 135 potential biomarkers.

In the active-disease group, the biomarkers that researchers identified were Tenascin C (TNC), CRP, TIMP1, leucine-rich alpha-2-glycoprotein 1, S100A8/A9, CD93, MMP9, and Transketolase (TKT).

TIMP1 was the optimal marker because it could differentiate between patients with even mildly active cases of the disease and patients in remission, the team said. Interestingly, TIMP1 levels were higher in active cases of ANCA-associated vasculitis than in infectious diseases. This could help doctors differentiate ANCA-associated vasculitis from other diseases, the team said.

When the researchers looked for biomarkers of organ damage, they discovered that blood serum levels of TKT and CD93 were higher in patients who had kidney damage. They concluded that the proteins could be used to predict kidney outcomes in ANCA-associated vasculitis.

Kidneys have a lot of TKT. High levels of the protein in serum indicates that kidney damage has led to TKT being released into the bloodstream. CD93 is found on the surface of immune cells. High levels of CD93 in blood may indicate an increase in immune-cell-triggered kidney inflammation.

Another study finding was high levels of TNC in ANCA-associated vasculitis patients with lung damage. This jibed with previous research that detected elevated levels of TNC in people with inflammatory lung conditions.

“Nine proteins—CRP, TIMP1, LRG1, TNC, S100A8/A9, MMP9, CD93, TKT, and MPO-ANCA—were identified as biomarkers of disease activity,” the team wrote. “Of these, TIMP1 was the best-performing biomarker of disease activity. Moreover, we identified TKT and CD93 as biomarkers for the evaluation of renal involvement and kidney outcome, as well as TNC as a biomarker reflecting lung infiltration in AAV.”

“AAV severity was associated with the levels of TKT, CD93, and TNC (markers reflecting organ involvement) rather than with inflammatory markers,” they wrote. The team said it expected the biomarkers to be “useful for therapeutic decision-making, monitoring of disease activity, and predicting” disease outcomes.