Inflammatory Protein, PTX3, May Be Potential AAV Diagnostic Biomarker
Significantly high levels of the inflammatory protein pentraxin-3 (PTX3) were found in the bloodstream and urine of people with ANCA-associated vasculitis (AAV), particularly those with kidney involvement, a study revealed.
Unlike C-reactive protein (CRP), a widely used inflammatory biomarker, PTX3 correlated with standard measures of AAV disease activity before treatment and was able to distinguish AAV patients with and without kidney involvement.
Based on these findings, researchers suggested that PTX3 may be a more suitable biomarker to support an AAV diagnosis.
The study, “Pentraxin-3 – a potential biomarker in ANCA-associated vasculitis,” was published in the Scandinavian Journal of Rheumatology.
In AAV, self-reactive antibodies target and activate immune cells called neutrophils, which trigger an immune response against the cells lining blood vessels, causing inflammation and damage. This type of vascular damage most commonly affects the kidneys, skin, and lungs.
Diagnosis can be challenging due to a wide range of symptoms, especially when multiple organs are involved. If AAV is suspected, blood can be tested to see if these self-reactive antibodies are present, as well as other markers for kidney function and inflammation.
Despite these tools, finding new inflammatory markers that closely reflect disease activity and specific organ involvement in AAV patients is still an unmet need.
CRP, which is mainly produced and released by the liver, is frequently used as an inflammatory biomarker in AAV because its concentration in the bloodstream rises in response to inflammatory stimulation.
PTX3 is a protein similar to CRP and also rises in response to inflammatory stimuli. But, unlike CRP, PTX3 is produced in immune cells, including neutrophils, and in cells that line blood vessels and kidney tubules. As such, PTX3 may be a more suitable biomarker to reflect AAV-related disease activity and severity.
In previous cross-sectional studies, PTX3 levels were found to be higher in AAV patients with active disease than in those with inactive disease and healthy people serving as controls.
Researchers at the Karolinska University Hospital, Sweden, measured PTX3 levels in 79 patients with newly diagnosed or relapsing AAV over six months to examine its relationship with disease activity and treatments initiated at diagnosis.
“To the best of our knowledge, this is the first longitudinal study to investigate PTX3 levels in patients with AAV in relation to the disease activity and immunosuppressive treatment,” the research team wrote.
They analyzed 43 men and 36 women with active AAV, ranging in age from 19 to 86. From these, 70 were newly diagnosed and nine had relapsed. All tested positive for self-reactive antibodies and all received immunosuppressant glucocorticoid therapy, with some receiving various initial anti-inflammatory medications.
Disease activity, as assessed with the Birmingham Vasculitis Activity Score (BVAS), decreased from a median of 15 points at the beginning of the study (baseline) to a median of 0 six months later, defined as complete remission, or no disease activity. Five patients failed to reach complete remission at follow-up.
At baseline, median PTX3 levels in blood samples collected from patients were significantly higher than at follow-up (median of 2.85 vs. 1.23 nanograms per milliliter (ng/mL)). PTX3 levels at baseline were also more elevated in newly diagnosed patients than in those with relapsing disease.
PTX3 concentrations were also significantly higher in patients compared to blood samples collected from a group of 23 healthy individuals at both time points.
Elevated PTX3 in the urine at baseline significantly correlated to higher (worse) BVAS scores. No significant differences in urinary PTX3 levels were seen at follow-up between patients who were in remission and those with active disease.
No statistical relationship was found between PTX3 in blood and urine samples at baseline.
Among 47 participants with kidney involvement at baseline, blood and urinary PTX3 levels were significantly higher than those without kidney problems.
A correlation was also found between blood PTX3 and various markers of kidney function, such as creatinine, eGFR, and albumin at baseline, but not at follow-up. Similar relationships between urinary PTX3 and eGFR and albumin were also seen.
As a comparison, the team measured CRP levels and found they decreased from baseline to six months. However, PTX3 did not significantly correlate with CRP, and there was no correlation between CRP levels and BVAS at baseline. Moreover, there was no difference in CRP levels between patients with and without kidney involvement or those who were newly diagnosed or had relapsed.
“[Blood] and urinary PTX3 levels were significantly increased in active AAV disease, and in particular in patients with kidney involvement,” the authors wrote. “Furthermore, both [blood] and urinary PTX3 levels seem to reflect disease activity in active AAV better than the commonly used CRP.”
“Future studies should include long-term follow-up to assess whether PTX3 may also have a role in detecting AAV relapses at an early stage,” they wrote.