Clinical Utility of Serial Measurements of Antineutrophil Cytoplasmic Antibodies Targeting Proteinase 3 in ANCA-Associated Vasculitis

• Published in: Frontiers in immunology Vol. 11; p. 2053
• Main Authors: Thompson, Gwen E, Fussner, Lynn A, Hummel, Amber M, Schroeder, Darrell R, Silva, Francisco, Snyder, Melissa R, Langford, Carol A, Merkel, Peter A, Monach, Paul A, Seo, Philip, Spiera, Robert F, St Clair, E William, Stone, John H, Specks, Ulrich
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 03-09-2020
• Subjects: ANCA-associated vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - diagnosis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - drug therapy; Antibodies, Antineutrophil Cytoplasmic - blood; biomarker; Biomarkers - blood; Cyclophosphamide - therapeutic use; Humans; Immunoassay; Immunology; Immunosuppressive Agents - therapeutic use; Myeloblastin - immunology; PR3-ANCA; relapse activity; remission; Rituximab - therapeutic use; Serologic Tests - methods; relapse activity; PR3-ANCA; biomarker; ANCA-associated vasculitis; remission
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2020.02053

The utility of ANCA testing as an indicator of disease activity in ANCA-associated vasculitis (AAV) remains controversial. This study aimed to determine the association of ANCA testing by various methods and subsequent remission and examine the utility of a widely used automated addressable laser-bead immunoassay (ALBIA) to predict disease relapses.
Data from the Rituximab vs. Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial were used. ANCA testing was performed by direct ELISA, capture ELISA, and ALBIA. Cox proportional hazards regression models were used to evaluate the association of PR3-ANCA level and subsequent remission or relapse. The ALBIA results are routinely reported as >8 when the value is high. For this study, samples were further titrated. A decrease and increase in PR3-ANCA were defined as a halving or doubling in value, respectively.
A decrease in ANCA by ALBIA at 2 months was associated with shorter time to sustained remission (HR 4.52,
= 0.035). A decrease in ANCA by direct ELISA at 4 months was associated with decreased time to sustained remission (HR 1.77,
= 0.050). There were no other associations between ANCA decreases or negativity and time to remission. An increase in PR3-ANCA by ALBIA was found in 78 of 93 subjects (84%). Eleven (14%) had a PR3-ANCA value which required titration for detection of an increase. An increase of ANCA by ALBIA was associated with severe relapse across various subgroups.
A decrease in ANCA by ALBIA at 2 months and by direct ELISA at 4 months may be predictive of subsequent remission. These results should be confirmed in a separate cohort with similarly protocolized sample and clinical data collection. A routinely used automated ALBIA for PR3-ANCA measurement is comparable to direct ELISA in predicting relapse in PR3-AAV. Without titration, 14% of the increases detected by ALBIA would have been missed. Titration is recommended when this assay is used for disease monitoring. The association of an increase in PR3-ANCA with the risk of subsequent relapse remains complex and is affected by disease phenotype and remission induction agent.