Motoki Yukari, Kaneshige Risa, Fujieda Yuichiro, Oku Kenji, Morishita Eriko, Ieko Masahiro, Atsumi Tatsuya, Ichihara Kiyoshi, Nojima Junzo
Department of Laboratory Science, Faculty of Health Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
PLoS One. 2025 Jul 24;20(7):e0328229. doi: 10.1371/journal.pone.0328229. eCollection 2025.
In 2023, international rheumatology societies issued new classification criteria for antiphospholipid syndrome (APS). The criteria require scoring antiphospholipid antibody (aPL) titers as moderate or high using the traditional thresholds of 40U or 80U determined by "standardized" ELISA. With current popularity of non-standardized aPL assays (non-ELISA), we aimed to broaden the application of the criteria by estimating equivalent thresholds for them.
Four types of aPLs (aCL/aβ2GPI-IgG/IgM) were measured using six reagents in 50 APS and 50 non-APS patients. By regression analysis of measurements between standardized ELISA and non-ELISA assays, thresholds equivalent to 10, 20, 40 and 80U were estimated for each assay. Data points below the detection limit of each assay were excluded from the regression. The diagnostic thresholds were also evaluated using "specificity-based" method described by the International Society on Thrombosis and Haemostasis (ISTH). This approach allegedly estimates diagnostic thresholds that attain predefined specificities of 0.975 and 0.995 in distinguishing APS from non-APS cases, respectively corresponding to moderate and high titers. The between-assay concordance of diagnostic classification using the estimated thresholds was calculated as kappa coefficient (κ).
Using major-axis regression, thresholds equivalent to the traditional units (10 - 80U) were estimated for non-ELISA assays, which led to harmonized semi-quantitative classification with high κ values. Conversely, the specificity-based method yielded thresholds that dissociated from the traditional ones, particularly for IgG-isotype assays, resulting in lower κ values than regression-based method (P = 0.0039 - 0.0098).
The regression-based conversion of diagnostic thresholds is practical in harmonizing diagnostic classification across major aPL assays. The specificity-based method may need adjusted predefined-specificities to estimate thresholds that are equivalent to the traditional thresholds.
2023年，国际风湿病学会发布了抗磷脂综合征（APS）的新分类标准。该标准要求使用“标准化”酶联免疫吸附测定（ELISA）确定的40U或80U传统阈值将抗磷脂抗体（aPL）滴度评为中度或高度。鉴于目前非标准化aPL检测方法（非ELISA）的广泛使用，我们旨在通过估计其等效阈值来扩大该标准的应用范围。
使用六种试剂对50例APS患者和50例非APS患者检测四种类型的aPL（aCL/aβ2GPI-IgG/IgM）。通过对标准化ELISA和非ELISA检测结果进行回归分析，估计每种检测方法相当于10、20、40和80U的阈值。将每种检测方法检测限以下的数据点排除在回归分析之外。还使用国际血栓与止血学会（ISTH）描述的“基于特异性”的方法评估诊断阈值。据称，这种方法估计的诊断阈值在区分APS与非APS病例时分别达到预定义的0.975和0.995的特异性，分别对应于中度和高度滴度。使用估计阈值进行诊断分类的检测方法间一致性计算为kappa系数（κ）。
使用主轴回归法估计了非ELISA检测方法相当于传统单位（10 - 80U）的阈值，从而实现了具有高κ值的统一半定量分类。相反，基于特异性的方法得出的阈值与传统阈值不同，特别是对于IgG同种型检测，导致κ值低于基于回归的方法（P = 0.0039 - 0.0098）。
基于回归的诊断阈值转换对于统一主要aPL检测方法的诊断分类是可行的。基于特异性的方法可能需要调整预定义特异性以估计与传统阈值等效的阈值。
