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Clinical Utility of Serial Measurements of Antineutrophil Cytoplasmic Antibodies Targeting Proteinase 3 in ANCA-Associated Vasculitis
Indexado
WoS WOS:000570546700001
Scopus SCOPUS_ID:85091122508
DOI 10.3389/FIMMU.2020.02053
Año 2020
Tipo artículo de investigación

Citas Totales

Autores Afiliación Chile

Instituciones Chile

% Participación
Internacional

Autores
Afiliación Extranjera

Instituciones
Extranjeras


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.

Revista



Revista ISSN
Frontiers In Immunology 1664-3224

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Disciplinas de Investigación



WOS
Immunology
Scopus
Sin Disciplinas
SciELO
Sin Disciplinas

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Publicaciones WoS (Ediciones: ISSHP, ISTP, AHCI, SSCI, SCI), Scopus, SciELO Chile.

Colaboración Institucional



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Autores - Afiliación



Ord. Autor Género Institución - País
1 Thompson, Gwen E. Mujer Essentia Hlth - Estados Unidos
Mayo Clin & Mayo Fdn Res & Educ - Estados Unidos
Mayo Clinic - Estados Unidos
Essentia Health - Estados Unidos
2 Fussner, Lynn A. Mujer OHIO STATE UNIV - Estados Unidos
The Ohio State University - Estados Unidos
3 Hummel, Amber M. Mujer Mayo Clin & Mayo Fdn Res & Educ - Estados Unidos
Mayo Clinic - Estados Unidos
4 Schroeder, Darrell R. Hombre Mayo Clin & Mayo Fdn Res & Educ - Estados Unidos
Mayo Clinic - Estados Unidos
5 SILVA-LABRA, FRANCISCO ANDRES Hombre Universidad del Desarrollo - Chile
Facultad de Medicina Clínica Alemana Universidad del Desarrollo - Chile
6 Snyder, Melissa R. Mujer Mayo Clin & Mayo Fdn Res & Educ - Estados Unidos
Mayo Clinic - Estados Unidos
7 Langford, C. A. Mujer CLEVELAND CLIN - Estados Unidos
Cleveland Clinic Foundation - Estados Unidos
8 Merkel, Peter A. Hombre UNIV PENN - Estados Unidos
University of Pennsylvania - Estados Unidos
9 Monach, Paul A. Hombre Brigham & Womens Hosp - Estados Unidos
Brigham and Women's Hospital - Estados Unidos
10 Seo, Philip Hombre Johns Hopkins Univ - Estados Unidos
Johns Hopkins University - Estados Unidos
11 Spiera, Robert F. Hombre Hosp Special Surg - Estados Unidos
Hospital for Special Surgery - New York - Estados Unidos
12 St Clair, E. William - Duke Univ - Estados Unidos
Duke University - Estados Unidos
Duke University School of Medicine - Estados Unidos
13 Stone, John H. Hombre MASSACHUSETTS GEN HOSP - Estados Unidos
Massachusetts General Hospital - Estados Unidos
14 Specks, Ulrich Hombre Mayo Clin & Mayo Fdn Res & Educ - Estados Unidos
Mayo Clinic - Estados Unidos

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Financiamiento



Fuente
National Institutes of Health
Johns Hopkins University
National Institute of Allergy and Infectious Diseases
National Center for Advancing Translational Sciences
Immune Tolerance Network
National Center for Research Resources
National Institute of Arthritis and Musculoskeletal and Skin Diseases
Boston University
Mayo Clinic
Arthritis Foundation
Mayo Foundation for Medical Education and Research
NCRR
Genentech, Inc.
Clinical and Translational Science Award from the National Center for Research Resources (NCRR)
CTSA Grant from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH)
Biogen IDEC, Inc.
Arthritis Foundation Investigator Award
Connor Group Foundation
Mayo Foundation for Research and Education
Clinical and Translational Science Award grants from the National Institutes of Health

Muestra la fuente de financiamiento declarada en la publicación.

Agradecimientos



Agradecimiento
The original rituximab versus cyclophosphamide for ANCA-associated vasculitis (RAVE) trial, from which the serum samples and clinical data was obtained, was supported by a grant from the National Institute of Allergy and Infectious Diseases to the Immune Tolerance Network (N01-AI-15416; protocol no. ITN021AI). Genentech, Inc. and Biogen IDEC, Inc. provided the study medications and partial funding. At the Mayo Clinic and Foundation, the trial was supported by a Clinical and Translational Science Award from the National Center for Research Resources (NCRR) (RR024150-01); at Johns Hopkins University, by grants from the NCRR (RR025005) and career development awards (K24 AR049185, to JS, and K23 AR052820, to PS); and at Boston University, by a Clinical and Translational Science Award (RR 025771), grants from the National Institutes of Health (M01 RR00533) and a career development award (K24 AR02224, to PMe), and an Arthritis Foundation Investigator Award (to PMo). Enzyme-linked immunosorbent assay kits for antineutrophil cytoplasmic antibody testing were provided by Euroimmun (Lubeck, Germany). The RAVE trial was made possible by the CTSA Grant UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). The content of this project is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This project was supported by funds from the Mayo Foundation for Research and Education as well as Connor Group Foundation (to US).
Funding. The original rituximab versus cyclophosphamide for ANCA-associated vasculitis (RAVE) trial, from which the serum samples and clinical data was obtained, was supported by a grant from the National Institute of Allergy and Infectious Diseases to the Immune Tolerance Network (N01-AI-15416; protocol no. ITN021AI). Genentech, Inc. and Biogen IDEC, Inc. provided the study medications and partial funding. At the Mayo Clinic and Foundation, the trial was supported by a Clinical and Translational Science Award from the National Center for Research Resources (NCRR) (RR024150-01); at Johns Hopkins University, by grants from the NCRR (RR025005) and career development awards (K24 AR049185, to JS, and K23 AR052820, to PS); and at Boston University, by a Clinical and Translational Science Award (RR 025771), grants from the National Institutes of Health (M01 RR00533) and a career development award (K24 AR02224, to PMe), and an Arthritis Foundation Investigator Award (to PMo). Enzyme-linked immunosorbent assay kits for antineutrophil cytoplasmic antibody testing were provided by Euroimmun (Lubeck, Germany). The RAVE trial was made possible by the CTSA Grant UL1 TR000135 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). The content of this project is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This project was supported by funds from the Mayo Foundation for Research and Education as well as Connor Group Foundation (to US).

Muestra la fuente de financiamiento declarada en la publicación.