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Page 6 of 14 Almeida et al. Vessel Plus 2021;5:44 https://dx.doi.org/10.20517/2574-1209.2021.66
Table 2. Anti-neutrophil cytoplasmic antibody-associated vasculitis biomarkers and their usefulness
Approach Biomarker Function Description
Diagnosis PR3-ANCA and MPO-ANCA Distinguish from healthy patients Present in patients with GPA and MPA subtypes,
and between AAV subtypes respectively
cfDNA Distinguish between AAV Increased levels of cfDNA in PR3-ANCA GPA patients
subtypes compared to
sCD163 Distinguish from healthy patients Higher urinary levels of sCD163 in patients with AAV
Eotaxin-3, IgG4 and Distinguish between AAV Increased levels of Eotaxin-3, IgG4 and CCL17/TARC in
CCL17/TARC subtypes EGPA compared to other AAV subtypes
12-HETE Distinguish between AAV Higher exhaled breath concentrations of 12-HETE in EGPA
subtypes patients than healthy patients
Prognosis Recognizable N-terminus of Evaluate disease prognosis Recognizable N-terminus of MPO heavy chain are more
MPO heavy chain prone to develop severe disease
C3 Evaluate disease prognosis Low serum C3 levels is associated with poorer outcomes
Disease activity PTX3+ and HMGB+ Distinguish disease activity status Concentrations of PTX3+ and HMGB+ were higher in
active AAV compared to remission
cfDNA Distinguish disease activity status Concentration levels are higher in disease activity phases
namely in PR3-ANCA positive GPA
MCP-1, AGP, KIM-1, NGAL Detect renal flares Urinary levels of MCP-1, AGP, KIM-1, NGAL are increased
in renal flares of AAV
sCD163 Distinguish disease activity status Higher urinary levels of sCD163 in disease activity phases
ESR, CRP and Calprotectin Distinguish disease activity status Higher levels of ESR, CRP and Calprotectin in disease
activity phases
Eotaxin-3, IgG4 and Distinguish disease activity status Increased levels of Eotaxin-3, IgG4 and CCL17/TARC in
CCL17/TARC disease activity phases
sRAGE Distinguish disease activity status Assessing mild/limited disease activity
EMPs and CECs Distinguish disease activity status EMPs and CECs levels positively correlate with disease
activity
+ +
CD25 T-cells Distinguish disease activity status CD25 T-cells inversely correlate with disease activity
Th17 cells Th17 cells positively correlate with disease activity
T follicular helper (Tfh) cells Distinguish disease activity status Tfh cells positively correlate with disease activity
Tfh2/Tf1 ratio Tfh2/Tfh1 ratio shift
Bb, C3a, C5a and soluble Distinguish disease activity status Bb, C3a, C5a and soluble C5b-9 urinary levels positively
C5b-9 relate with disease activity.
Relapse risk PR3-ANCA Evaluate relapse risk Increased PR3-ANCA levels positively relate with higher
relapse risk
Calprotectin Evaluate relapse risk Elevated calprotectin levels in patients who relapsed
EPCs Evaluate relapse risk Reduced levels of EPCs positively relate with higher relapse
risk
B-cells Evaluate relapse risk Incomplete B-cell depletion and B-cell repopulation after
rituximab treatment relate with higher relapse rate
CD8+ T-cells Evaluate relapse risk CD8+ T-cells levels positively relate with higher relapse
risk
Response to PR3-ANCA Evaluate response to treatment PR3-ANCA positive respond better to treatment with
treatment Rituximab
GPA: Granulomatosis with polyangiitis; MPO: myeloperoxidase; ANCA: anti-neutrophil cytoplasmic antibody; MPA: microscopic polyangiitis;
AAV: associated vasculitides; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; EGPA: eosinophilic GPA; EMPs: endothelial
microparticles; EPCs: endothelial progenitor cells.
ANCA
The value of ANCA as a diagnostic marker is mainly irrefutable. Occasional cases of “ANCA-negative”
AAV are acknowledged, decreasing by the day with ANCA testing methodology improvement [36,37] . False-
negative results can still be found because in some cases ANCA binds to the circulating ceruloplasmin .
[38]