Table 1.
Strengths and weaknesses of potential biomarkers (in alphabetical order).
| Biomarker | Potential utility | Pitfalls |
|---|---|---|
| ANCA (serum) | Diagnostic value is well established | Discordance with disease activity: -Persistent positivity of ANCA in remission disease -Significance of reappearance of ANCA - Seronegative disease |
| Anti-LAMP2 Ab (serum) | Potential role in pathogenesis and association with disease activity | Limited role of “minor ANCA” |
| Anti-PLG Ab (serum) | Associated with higher degree of acute inflammatory renal lesion (potential biomarker of renal severity) | Associated with ANCA seropositivity; Unknown prognostic utility |
| Anti-PTX-3 Ab (serum) | Proposed role as a diagnostic biomarker in ANCA-negative AAV; Potential in distinguishing disease activity status |
Lack of widespread routine tests (need for reference laboratory) |
| BAFF (serum) | Potential therapeutical role of anti-BAFF agents | Conflicting data between correlation of BAFF levels and disease activity in AAV |
| Bregs and naïve B-cells | Crucial in maintaining self-tolerance; Inverse correlation between CD5+ B-cells and disease activity; Lower relapse risk with repopulation of naïve CD19+CD27- B-cells |
Role limited to patients treated with RTX; Need for reference laboratory and sensitive flow cytometry method |
| CECs | Correlation with disease activity | Lack of widespread routine tests |
| Complement fractions | Correlation with disease activity (Bb, C3a, C5a, and soluble C5b-9); Prognostic value in renal involvement (serum C3 levels); Therapeutic target (C5a receptor) |
Not association between serological and pathohistological phenotypes and serum C3 levels |
| EMPs | Correlation with disease activity | Lack of widespread routine tests |
| EPCs | Inverse correlation between EPCs levels and relapse risk | Lack of widespread routine tests |
| sCD163 (urine) | High sensitivity and specificity for active renal vasculitis | Limited role in renal involvement disease; Does not distinguish infection from relapse; Not disease-specific (has also been studied in SLE) |
| S100A8/S100A9 (serum) | Correlation with disease activity | Reduction but not normalization into disease remission (subclinical inflammation)?; Not disease-specific |
| T-cells | Inverse correlation between CD25+ T-cells and disease activity; Correlation between Th17 cells and disease activity; Correlation between CD8+ T-cells levels and relapse risk |
Further researches are needed |
| uMCP-1 (urine) | Proposed role in renal AAV disease activity; Increasing levels during renal flare of disease |
Limited role in renal involvement disease |
ANCA, anti-neutrophil cytoplasmic antibody; Ab, antibodies; BAFF, B-cell activating factor; Bregs, regulatory B-cells; CECs, circulating detached mature endothelial cells; EGPA, eosinophilic granulomatosis with polyangiitis; EMPs, endothelial microparticles; EPCs, endothelial progenitor cells; LAMP2, lysosome-associated membrane protein-2; uMCP-1, urinary monocytes chemoattractant protein-1; PLG, plasminogen; PTX-3, pentraxin-3; sCD163, soluble CD163; S100A8/S100A9, calprotectin.