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| 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
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.
| 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 |
| 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 |
| 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). |