Immune protein is prognosis sign in ANCA-associated vasculitis
CCL23 levels are increased in people with disease relative to healthy people
Blood levels of CCL23, an immune molecule that may be involved in blood vessel formation and repair, are significantly increased in people with ANCA-associated vasculitis (AAV) relative to healthy people, a study finds.
High blood CCL23 levels accurately differentiate people with active AAV from those in remission and increase the risk of AAV relapse and kidney involvement, showing they can predict disease prognosis. While it’s unclear how CCL23 is linked to developing AAV, the findings suggest the immune protein could serve as a blood biomarker for the disease’s diagnosis and prognosis, according to the study’s researchers.
“Increase in CCL23 level indicate increases in disease activity, risk of disease relapse, and severity of organ or system involvement, all of which may be important factors in poor disease prognosis,” they wrote. The study, “CCL23 is a potential biomarker for antineutrophil cytoplasmic antibody–associated vasculitis,” was published in Arthritis Research & Therapy.
AAV is a group of autoimmune diseases marked by inflammation and damage to small blood vessels that may affect several organs. The inflammation is typically caused by ANCAs, self-reactive antibodies that target either the myeloperoxidase (MPO) or proteinase 3 (PR3) enzymes.
It’s been suggested that chemokines, small molecules released by immune cells that direct the movement of other immune cells to sites of infection and injury, may contribute to lasting inflammation in AAV. A specific chemokine, called CCL23, is increased in people with AAV.
Investigating CCL23 levels
Here, researchers in China investigated if blood CCL23 levels could be used as markers of AAV disease activity and prognosis. They analyzed data from 317 AAV patients who visited the First Affiliated Hospital of Zhengzhou University between August 2021 and June 2024, and from 83 healthy people, who served as controls. Both the patient and control groups had a slightly higher proportion of females, and the patients were significantly older than the healthy participants (median age, 67 vs. 46).
In terms of AAV types, most patients (79.8%) had microscopic polyangiitis (MPA), while the remaining 20.2% had granulomatosis with polyangiitis (GPA). Most had ANCAs that target MPO (60.3%), while 14.2% had anti-PR3 ANCAs.
Among the patients, the main disease manifestation was lung involvement (77.9%), followed by kidney (43.5%), nervous system (20.5%), and ear, nose, and throat involvement (20.5%).
Blood levels of CCL23 were significantly higher among people with AAV. After adjusting for age and sex, the researchers found that the probability of having AAV increased by 51.1% for every 1 ng/mL increase in CCL23. High CCL23 levels could differentiate people with AAV from healthy people with an accuracy of 89%. Also, blood CCL23 levels were significantly higher in people with MPA than with GPA, and in patients with anti-MPO ANCAs than those without such antibodies.
Active disease vs. disease remission, prognosis
Chemokine levels were also higher in patients with active disease than in those in remission, and in patients with high disease activity relative to those with low disease activity, as assessed with the Birmingham Vasculitis Activity Score (BVAS).
Also, the BVAS of patients with anti-MPO ANCAs was significantly higher than that in the patients without such antibodies, confirming that “elevated CCL23 in [MPO-positive] patients may be associated with higher disease activity,” the researchers wrote.
Higher CCL23 levels were significantly associated with higher BVAS, along with higher erythrocyte sedimentation rate and higher C-reactive protein levels — two general markers of inflammation.
To further determine the link between CCL23 levels and disease status, the researchers randomly assessed CCL23 levels in 18 patients with active disease, before and after they achieved disease remission. CL23 levels significantly decreased after induced remission, they found.
Both BVAS and CCL23 levels were able to effectively differentiate patients in remission from those having a relapse, but CCL23 did so with greater accuracy (94.2% vs. 84%).
Also, a cutoff CCL23 value of 24.63 nanograms per milliliter (ng/mL) could differentiate patients with poor prognosis within a one-year follow-up from those with good prognosis with an accuracy of 77.5%. Poor outcomes included progression to kidney failure, acute respiratory failure, and death due to AAV complications. CCL23 levels higher than the cutoff were also significantly associated with a higher risk of poor prognosis.
Moreover, the risk of kidney involvement increased by 72.2% per each 10 ng/mL increase in CCL23 levels. There was no significant link between CCL23 levels and lung involvement.
“The detection of CCL23 as a biomarker for AAV patients may be an important method to help early diagnosis of AAV, and is of great value for evaluating disease activity and [kidney] involvement after the onset of AAV and predicting disease prognosis,” the researchers wrote. “Our findings supported further investigation of CCL23 as a biomarker of AAV and potential therapeutic target.”
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