Serum Progranulin as a Potential Marker for Disease Activity and Thrombotic Events in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Abstract

Objective: Progranulin (PGRN) is a secreted glycoprotein that can have pro-inflammatory or anti-inflammatory effects, depending on the disease. The serum and urinary levels and mechanism of action of PGRN in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are unclear.

Methods: Thirty patients with active AAV were enrolled from May 2022 to May 2024; 28 were myeloperoxidase-positive, and two were proteinase 3-positive. A healthy control cohort consisted of five male and five female volunteers. Age, gender, AAV subtype, and laboratory data were collected. Using an enzyme-linked immunosorbent assay, Whole blood and urine samples were collected for measurements of PGRN.

Results: The median patient age was 69.0 years (range: 58.8-75.5); 56.7% of them were female, and 94.3% of them were MPO-ANCA-positive. Compared with healthy controls, the AAV patients had higher serum PGRN levels (52.0±30.9 vs. 3.3±1.7 ng/mL, P<0.05) and lower urinary PGRN levels. The serum PGRN level also had a positive correlation with the Birmingham vasculitis activity score (r=0.776, P<0.001), and moderate positive correlations with coagulation-related parameters (activated partial thromboplastin time, fibrin degradation products, and D-dimer). Patients who subsequently developed thrombotic events had higher serum PGRN levels than those without thrombotic events.

Conclusion: The serum PGRN level was associated with disease activity and coagulation abnormalities in patients with active AAV, particularly in those with MPO-ANCA positivity. Although serum PGRN had a positive association with thrombotic events, its elevation may be influenced by renal dysfunction and systemic inflammation. Therefore, serum PGRN may serve as an activity-related biomarker rather than a disease-specific marker in AAV.