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Diagnostic accuracy of ANCA serology in ANCA-associated vasculitis with renal involvement
Adrienne Cohen1, Nethmi Weerasinghe1, Karla Lemmert2
1Department of Nephrology and Renal Transplant, John Hunter Hospital, Newcastle, New South Wales, Australia.
Insights
Serum antineutrophil cytoplasmic antibody (ANCA) titres are highly predictive of pauci-immune glomerulonephritis (GN) in patients with ANCA-associated vasculitis (AAV). Quantifying ANCA titres can aid early treatment decisions for severe kidney disease.
Area of Science:
- Nephrology
- Immunology
- Vasculitis
Background:
- Pauci-immune glomerulonephritis (GN) in ANCA-associated vasculitis (AAV) has high mortality and progression rates.
- Kidney biopsy is standard for diagnosing renal involvement in AAV.
- The predictive value of serum ANCA quantification for renal involvement is unclear.
Purpose of the Study:
- To assess the diagnostic accuracy of serum ANCA titres for AAV with renal involvement.
- To determine the utility of ANCA quantification in AAV diagnosis.
Main Methods:
- Retrospective analysis of native kidney biopsies and ANCA serology from 2016-2021.
- ANCA titres measured by indirect immunofluorescence; specific antibodies by chemiluminescent immunoassay.
- Included adult patients with both kidney biopsy and ANCA serology.
Main Results:
- 8.1% of 507 patients had pauci-immune GN.
- Positive ANCA at any titre showed 97.6% sensitivity and 71.2% specificity for pauci-immune GN.
- An ANCA titre cutoff of 1:160 offered optimal sensitivity (75.6%) and specificity (94.0%).
Conclusions:
- Serum ANCA titres are highly predictive of pauci-immune GN.
- ANCA quantitation aids early treatment decisions in AAV with organ- or life-threatening disease.
- While not replacing biopsy, ANCA titres are valuable diagnostic adjuncts.
Background:
Pauci-immune glomerulonephritis (GN) due to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a common cause of crescentic GN. Despite advances in treatment, rates of mortality and progression to end-stage kidney disease remain high. Renal involvement is diagnosed by histological examination of kidney tissue. Serum ANCAs play a significant role in AAV; however, the value of serum ANCA quantification to predict renal involvement is not well-established.
Aim:
We aimed to evaluate the diagnostic accuracy of serum ANCA titres in diagnosing AAV with renal involvement.
Methods:
We conducted a retrospective study of consecutive native kidney biopsies reported at our centre from 2016 to 2021. We included all adults who had both a kidney biopsy and ANCA serology. ANCA serology was tested using indirect immunofluorescence with reporting of titres. Antibodies to proteinase 3 and myeloperoxidase were measured using a chemiluminescent immunoassay.
Results:
Eight hundred and forty-eight native kidney biopsies were reported during the study period. Five hundred and seven cases were included. The biopsy prevalence of pauci-immune GN in paired samples was 41/507 (8.1%). Most of the cohort had haematuria (66.6%), proteinuria (93.4%) and/or acute kidney injury (65.0%). A positive ANCA at any titre demonstrated a sensitivity of 97.6% and a specificity of 71.2% for a diagnosis of pauci-immune GN. The area under the curve for the receiver operator characteristic was 0.93 (95% confidence interval [CI]: 0.89-0.97). A cutoff ANCA titre of 1:160 provided the optimum balance between a sensitivity of 75.6% (95% CI: 59.7%-87.6%) and a specificity of 94.0% (95% CI: 91.6%-96.0%).
Conclusions:
ANCA titres are highly predictive of pauci-immune GN in the appropriate context. While serum ANCA quantitation may not replace renal biopsy, reporting will assist in the decision to start treatment early for patients with organ or life-threatening disease.
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