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

Abstract

Background: 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. Methods: 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. Results: A decrease in ANCA by ALBIA at 2 months was associated with shorter time to sustained remission (HR 4.52, p = 0.035). A decrease in ANCA by direct ELISA at 4 months was associated with decreased time to sustained remission (HR 1.77, p = 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. Conclusions: 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.

• Authors: Gwen E Thompson, Lynn A Fussner, Amber M Hummel, Darrell R Schroeder, Francisco Silva, Melissa R Snyder, Carol A Langford, Peter A Merkel, Paul A Monach, Philip Seo, Robert F Spiera, E William St Clair, John H Stone, Ulrich Specks
• Journal: Frontiers in immunology (Front Immunol) Vol. 11 Pg. 2053 ( 2020) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 33013868 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Thompson, Fussner, Hummel, Schroeder, Silva, Snyder, Langford, Merkel, Monach, Seo, Spiera, St. Clair, Stone and Specks.

Chemical References

• Antibodies, Antineutrophil Cytoplasmic
• Biomarkers
• Immunosuppressive Agents
• Rituximab
• Cyclophosphamide
• Myeloblastin

Topics

• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis (diagnosis, drug therapy)
• Antibodies, Antineutrophil Cytoplasmic (blood)
• Biomarkers (blood)
• Cyclophosphamide (therapeutic use)
• Humans
• Immunoassay
• Immunosuppressive Agents (therapeutic use)
• Myeloblastin (immunology)
• Rituximab (therapeutic use)
• Serologic Tests (methods)