Thompson Gwen E, Fussner Lynn A, Hummel Amber M, Schroeder Darrell R, Silva Francisco, Snyder Melissa R, Langford Carol A, Merkel Peter A, Monach Paul A, Seo Philip, Spiera Robert F, St Clair E William, Stone John H, Specks Ulrich
Essentia Health, Division of Pulmonary and Critical Care, Fargo, ND, United States.
Mayo Clinic and Mayo Foundation for Research and Education, Rochester, MN, United States.
Front Immunol. 2020 Sep 3;11:2053. doi: 10.3389/fimmu.2020.02053. eCollection 2020.
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. 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. A decrease in ANCA by ALBIA at 2 months was associated with shorter time to sustained remission (HR 4.52, = 0.035). A decrease in ANCA by direct ELISA at 4 months was associated with decreased time to sustained remission (HR 1.77, = 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. 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.
抗中性粒细胞胞浆抗体（ANCA）检测作为ANCA相关性血管炎（AAV）疾病活动指标的效用仍存在争议。本研究旨在确定采用各种方法进行ANCA检测与随后缓解之间的关联，并检验一种广泛使用的自动化可寻址激光珠免疫分析（ALBIA）预测疾病复发的效用。使用了利妥昔单抗与环磷酰胺治疗ANCA相关性血管炎（RAVE）试验的数据。通过直接酶联免疫吸附测定（ELISA）、捕获ELISA和ALBIA进行ANCA检测。采用Cox比例风险回归模型评估蛋白酶3-ANCA（PR3-ANCA）水平与随后缓解或复发之间的关联。当ALBIA结果值高时，通常报告为>8。在本研究中，对样本进行了进一步滴定。PR3-ANCA的降低和升高分别定义为值减半或翻倍。2个月时ALBIA检测的ANCA降低与达到持续缓解的时间缩短相关（风险比4.52，P = 0.035）。4个月时直接ELISA检测的ANCA降低与达到持续缓解的时间减少相关（风险比1.77，P = 0.050）。ANCA降低或转阴与缓解时间之间无其他关联。93名受试者中有78名（84%）通过ALBIA检测到PR3-ANCA升高。11名（14%）受试者的PR3-ANCA值需要滴定才能检测到升高。ALBIA检测到的ANCA升高与各亚组的严重复发相关。2个月时ALBIA检测的ANCA降低以及4个月时直接ELISA检测的ANCA降低可能预测随后的缓解。这些结果应在一个单独的队列中进行确认，该队列应具有类似规范化的样本和临床数据收集。用于PR3-ANCA测量的常规使用的自动化ALBIA在预测PR3-AAV复发方面与直接ELISA相当。如果不进行滴定，ALBIA检测到的升高中有14%会被漏检。当该检测用于疾病监测时，建议进行滴定。PR3-ANCA升高与随后复发风险之间的关联仍然复杂，并且受疾病表型和缓解诱导剂的影响。
