Immune protein CX3CL1 may be biomarker of active MPA, GPA

High blood levels found to discriminate those with, without active disease

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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High blood levels of the protein CX3CL1, a pro-inflammatory immune signal that appears to be associated with blood vessel inflammation, can accurately discriminate microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) patients with active disease from those without, a study found.

Importantly, high CX3CL1 levels were found to increase the likelihood of having active disease by more than 27 times among patients with either MPA or GPA — the two most common types of ANCA-associated vasculitis (AAV).

While it remains unknown how exactly CX3CL1 is linked to these AAV types, and whether its levels change upon treatment, the findings suggest that the immune protein could be used as a blood biomarker of active MPA and GPA, according to researchers.

The study, “Chemokine expression in sera of patients with microscopic polyangiitis and granulomatosis with polyangiitis,” was published in Scientific Reports.

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Scientists look for link between immune protein levels and disease activity

AAV occurs when self-reactive antibodies glom onto neutrophils, a type of immune cells, and prime them to launch an inflammatory attack that damages vulnerable small blood vessels in the body, causing symptoms affecting the kidneys and other organs.

Chemokines are small molecules that call neutrophils and other immune cells to sites of infection to help clear harmful microbes and restore order. There now is growing evidence that chemokines may contribute to lasting inflammation in autoimmune diseases like AAV.

Now, researchers in South Korea drew on data from the Severance Hospital ANCA-associated Vasculitides (SHAVE) study to watch for a link between certain chemokines in the blood and disease activity in MPA and GPA patients.

The study included 47 adults with MPA and 33 adults with GPA. The MPA patients were significantly older (median of 69 vs. 65 years), and were more likely to have had the disease for less than three months (87.2% vs. 51.5%).

Those in the MPA group were significantly more likely to have kidney involvement (85.1% vs. 33.3%), but ear, nose, and throat involvement was more frequent among GPA patients (51.5% vs. 21.3%).

People with MPA also had significantly more active disease, as indicated by higher scores in the Birmingham Vasculitis Activity Score, or BVAS (median of 16 vs. 6 points). The maximum possible score is 63 points, and the researchers considered that a score of at least 12 points represents active disease.

This group of patients also had significantly more severe disease, reflected by a higher median five-factor score, or FFS (2 vs. 1). FFS is a measure of the likely course of the disease, with scores ranging from 0 to 2 and higher scores indicating worse disease and an increased risk of death.

In addition, when compared with the 32 patients with inactive disease, the 48 patients with active disease were on average older (69 vs. 61 years) and more likely to have a short disease duration (91.7% vs. 43.8%) and kidney involvement (91.7% vs. 21.9%).

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Higher CX3CL1 levels seen to increase risk of active MPA/GPA by 27.4 times

The results showed that, among a total of six chemokines measured in the blood, the levels of CX3CL1 were on average significantly higher in patients with active disease (2,970.4 vs. 1,722.7 picograms/mL).

CX3CL1 is present at the surface of cells lining blood vessels, where it mediates neutrophil binding, and it has been linked to the infiltration of immune cells into kidneys damaged due to AAV.

Blood CX3CL1 levels were significantly higher in MPA patients relative to GPA patients (2780.3 vs. 1770.7 picograms/mL), patients with disease duration less than three months versus three months or longer (2726.5 vs. 1863.5 picograms/mL), and patients with kidney involvement.

CX3CL1 correlated with disease activity and was independently associated with active disease in patients with MPA/GPA. … [These findings] suggest that evaluating CX3CL1 levels could have clinical implications for predicting disease severity.

Further statistical analyses showed that higher blood CX3CL1 levels were significantly associated with higher BVAS and higher FFS, indicating more active and severe disease.

A cut-off CX3CL1 level of 2408.92 picograms/mL was able to discriminate patients with active MPA/GPA from those without active disease with an accuracy of about 80%. CX3CL1 levels greater than the cut-off increased the risk for active MPA/GPA by 27.4 times.

“CX3CL1 correlated with disease activity and was independently associated with active disease in patients with MPA/GPA,” the researchers wrote, adding that their findings “suggest that evaluating CX3CL1 levels could have clinical implications for predicting disease severity.”

This held true “even when laboratory tests that are generally performed during routine patient care were taken into account,” the team wrote, “indicating that CX3CL1 could serve as a potential biological marker for the evaluation of disease activity in MPA/GPA.”

Still, the analyses conducted in this study were “unable to address whether assessing CX3CL1 could be useful in monitoring treatment response and predicting disease-related outcomes,” the researchers wrote. Further research is needed to “explore these aspects.”