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

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dc.contributor.authorThompson, Gwen E
dc.contributor.authorFussner, Lynn A
dc.contributor.authorHummel, Amber M
dc.contributor.authorSchroeder, Darrell R
dc.contributor.authorSilva, Francisco
dc.contributor.authorSnyder, Melissa R
dc.contributor.authorLangford, Carol A
dc.contributor.authorMerkel, Peter A
dc.contributor.authorMonach, Paul A
dc.contributor.authorSeo, Philip
dc.contributor.authorSpiera, Robert F
dc.contributor.authorSt Clair, E William
dc.contributor.authorStone, John H
dc.contributor.authorSpecks, Ulrich
dc.date.accessioned2021-10-27T13:27:21Z
dc.date.available2021-10-27T13:27:21Z
dc.date.issued2020
dc.description.abstractBackground: 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.es
dc.identifier.citationFrontiers Immunology 2020 Sep 3;11:2053es
dc.identifier.urihttps://doi.org/10.3389/fimmu.2020.02053es
dc.identifier.urihttp://hdl.handle.net/11447/4944
dc.language.isoen_USes
dc.subjectANCA-associated vasculitises
dc.subjectPR3-ANCAes
dc.subjectbiomarkeres
dc.subjectrelapse activityes
dc.subjectremissiones
dc.titleClinical Utility of Serial Measurements of Antineutrophil Cytoplasmic Antibodies Targeting Proteinase 3 in ANCA-Associated Vasculitises
dc.typeArticlees

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