A growing body of research is shedding light on the hidden immune activity that persists even when patients with ANCA-associated vasculitis (AAV) appear to be in remission, raising hopes for earlier detection of disease relapse and more personalized treatment strategies.
A recent study published in Nefrología (English Edition) reports that two inflammatory biomarkers, urinary soluble CD163 (usCD163) and serum calprotectin, may help identify patients at higher risk of relapse despite clinically stable disease. The findings add to an evolving understanding of AAV as a condition marked not only by episodic flares but also by ongoing, low-grade immune activation.
Calprotectin, a heterodimer of S100A8 (MRP8) and S100A9 (MRP14), is released by activated monocytes and neutrophils and is widely recognized as a marker of innate immune activation. It plays an active role in vascular inflammation by binding to endothelial surfaces through heparan sulfate, triggering the release of proinflammatory cytokines such as TNF-α, IL-1β, IL-6, IL-23, and IL-8. This cascade promotes the expression of adhesion molecules like ICAM-1, enhances leukocyte recruitment, and contributes to endothelial injury and necrosis, which are hallmarks of vasculitic damage. CD163, in contrast, is a macrophage-specific scavenger receptor, and its soluble form reflects macrophage activation and inflammatory signaling through ectodomain shedding.
In the retrospective observational study, researchers analyzed 78 samples from 17 AAV patients in remission who were receiving rituximab as maintenance therapy. Using ELISA-based measurements, they found a significant positive correlation between serum calprotectin and usCD163 levels (p = 0.005), suggesting that both markers reflect overlapping inflammatory pathways. Both biomarkers also showed associations with C-reactive protein (CRP), a conventional marker of systemic inflammation, while usCD163 demonstrated an additional correlation with erythrocyte sedimentation rate (ESR), reinforcing its potential sensitivity to ongoing inflammatory processes.
Concentrations of both biomarkers were higher during the first six months following a disease flare, indicating that immunological activity may persist well beyond clinical remission. During follow-up, patients who later experienced relapse had higher mean levels of both biomarkers; however, statistical significance was reached only for usCD163 (p = 0.05), positioning it as a particularly promising predictor of impending disease activity.
The study also identified a temporal relationship with rituximab therapy. Serum calprotectin levels were significantly elevated in patients who had received rituximab within the previous three months compared with those treated 9 to 12 months earlier (p = 0.031). This finding suggests that biomarker levels may reflect not only disease biology but also treatment timing and immune reconstitution dynamics following B-cell depletion.
These results align with earlier research by Anton-Pampols and colleagues, who evaluated 138 patients with AAV and demonstrated that both serum calprotectin and urinary CD163 levels were significantly higher during active disease compared with remission. Importantly, their study showed that a combined model incorporating serum calprotectin, urinary CD163, and haematuria achieved the highest diagnostic accuracy, with strong sensitivity and specificity across both inception and validation cohorts. This multi-marker approach proved particularly effective in identifying active renal involvement, a critical determinant of long-term outcomes in AAV.
Experts note that these biomarkers could address a longstanding clinical challenge, distinguishing true remission from subclinical disease activity. Current monitoring strategies rely heavily on clinical assessment and traditional inflammatory markers, which may not fully capture ongoing vascular inflammation. Incorporating biomarkers such as calprotectin and usCD163 into routine follow-up could allow clinicians to detect early warning signs of relapse and adjust therapy proactively.
However, researchers caution that the current evidence remains preliminary. Future studies are also expected to explore how these biomarkers can be integrated into treatment algorithms, particularly in guiding rituximab dosing intervals and minimizing unnecessary immunosuppression.
If confirmed, these advances could mark a significant step toward precision medicine in ANCA-associated vasculitis, where treatment decisions are guided not only by symptoms but by real-time insights into the underlying immune landscape.
References
- Martinez Valenzuela L, Anton Pàmpols P, Gómez Preciado F, Fernandez-Juarez G, Fulladosa Oliveras X, Maria Cruzado J, et al. New insights into the evolution of serum calprotectin and urinary CD163 in ANCA-associated vasculitis during remission: An exploratory study. Nefrologia (Engl Ed). 2026 Apr;46(4):501472.
- Anton-Pampols P, Martínez Valenzuela L, Fernández Lorente L, Quero Ramos M, Gómez Preciado F, Martín Capón I, et al. Combining neutrophil and macrophage biomarkers to detect active disease in ANCA vasculitis: a combinatory model of calprotectin and urine CD163. Clin Kidney J. 2022 Dec 7;16(4):693-700.