Study points to 2 biomarkers for AAV disease activity, relapse
Calprotectin, usCD163 levels together may predict relapse from remission
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Blood levels of calprotectin and urine levels of soluble CD163, two biomarkers of inflammation and disease activity in people with ANCA-associated vasculitis (AAV), are elevated within the first six months following an AAV relapse, stabilizing thereafter.
That’s according to a recent study in Spain that also showed levels of urinary soluble CD163 (usCD163) were significantly higher in AAV patients who later relapsed than in those who did not. In addition, both blood calprotectin and usCD163 were influenced by the time that elapsed since the last administration of rituximab, an approved therapy for the most common AAV types.
The results “reinforce the potential utility of calprotectin and usCD163 as complementary biomarkers for understanding [AAV] disease dynamics,” the researchers wrote. “While neither marker alone clearly predicts relapse, elevated values during remission may indicate patients at higher risk.”
The study, “New Insights into the Evolution of Serum Calprotectin and Urinary CD163 in ANCA-Associated Vasculitis During Remission: an exploratory study,” was published in Nefrología.
AAV is a group of autoimmune diseases marked by inflammation and damage to small blood vessels, often leading to organ damage, particularly in the kidneys. AAV is caused in most cases when ANCAs, self-reactive antibodies that bind to immune cells called neutrophils, trigger an immune reaction against the cells that line blood vessels.
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Calprotectin is a protein released by activated immune cells, including neutrophils, that contributes to inflammatory processes in AAV. CD163 is a protein found at the surface of certain immune cells that is released, in its soluble form, during inflammation.
Previous studies in people with AAV have reported that blood calprotectin levels are associated with inflammation, disease activity, and worse kidney disease, and that usCD163 levels are linked to disease activity and kidney inflammation.
However, the dynamics of calprotectin and usCD163 levels during periods of AAV remission, when symptoms are well controlled, remain largely unclear.
To fill this knowledge gap, a team of researchers from a hospital in Barcelona retrospectively analyzed data from 17 AAV patients whose disease was in remission at the time of inclusion. Remission was defined as having a Birmingham Vasculitis Activity Score (BVAS) of zero, indicating no disease activity.
Participants had a mean age of 66.7 and were mainly women (70.6%). All were positive for ANCAs, most commonly targeting the myeloperoxidase protein (64.7%), had a kidney biopsy indicative of AAV, and were receiving rituximab as a maintenance therapy.
The patients were followed for an average of 306.8 days (about 10 months), during which a total of 73 samples were collected to measure the urine levels of soluble CD163 and blood levels of calprotectin.
Results showed that higher levels of calprotectin were significantly associated with higher levels of usCD163. Higher levels of either biomarker were significantly linked to higher blood levels of C-reactive protein, a marker of body-wide inflammation, and lower counts of lymphocytes, a type of immune cell.
There were also significant associations between higher usCD163 levels and a higher erythrocyte sedimentation rate, another marker of inflammation, and between higher calprotectin levels and several markers of worse kidney function.
Levels of usCD163 and calprotectin dropped during the first year of remission. Levels were significantly higher in samples collected in the first six months after a relapse than in samples collected more than six months later.
Four participants experienced relapses during follow-up. Those who relapsed had significantly higher usCD163 levels in remission than those who did not relapse, suggesting that the protein may predict patients at a higher risk of relapse.
From the initiation of remission maintenance therapy with rituximab until the end of the follow-up period, participants received a mean of 2.7 rituximab doses. Calprotectin levels were significantly higher in samples from patients who had received their last rituximab dose within the past three months compared with those whose last dose was given six to nine months or nine to 12 months prior.
A similar pattern was observed for usCD163 levels comparing samples obtained within three months after the last treatment dose with those obtained three to six months and six to nine months before.
In samples obtained only after six months in remission, calprotectin levels were significantly higher in patients who received rituximab less than three months before, compared with those who were last dosed nine to 12 months earlier. No significant differences were observed for usCD163.
According to the researchers, “the continued decline in these biomarkers over time, even after remission, the correlation between calprotectin levels and [kidney] function, and the higher levels of biomarkers in patients who later experienced a relapse … provide new insights into the … persistent immune activity associated with this disease.”
