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

Author

Front Immunol. 2020 Sep 3;11:2053. doi: 10.3389/fimmu.2020.02053. eCollection 2020.

Gwen E Thompson 1 2, Lynn A Fussner 3, Amber M Hummel 2, Darrell R Schroeder 2, Francisco Silva 4, Melissa R Snyder 2, Carol A Langford 5, Peter A Merkel 6 7, Paul A Monach 8, Philip Seo 9, Robert F Spiera 10, E William St Clair 11, John H Stone 12, Ulrich Specks 2

Author Information

1 Essentia Health, Division of Pulmonary and Critical Care, Fargo, ND, United States.

2 Mayo Clinic and Mayo Foundation for Research and Education, Rochester, MN, United States.

3 Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, OH, United States.

4 Department of Rheumatology, Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago, Chile.

5 Cleveland Clinic, Division of Rheumatology, Cleveland, OH, United States.

6 Division of Rheumatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, United States.

7 Division of Clinical Epidemiology, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, United States.

8 Division of Rheumatology, Brigham and Women's Hospital, Boston, MA, United States.

9 Division of Rheumatology, Johns Hopkins University, Baltimore, MD, United States.

10 Division of Rheumatology, Hospital for Special Surgery, New York, NY, United States.

11 Division of Rheumatology, Duke University, Durham, NC, United States.

12 Division of Rheumatology, Massachusetts General Hospital, Boston, MA, United States.

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.