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Abstract：
BACKGROUND: Two or more autoantibodies against either insulin (IAA), glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A) or zinc transporter 8 (ZnT8A) denote stage 1 (normoglycemia) or stage 2 (dysglycemia) type 1 diabetes prior to stage 3 type 1 diabetes. Automated multiplex Antibody Detection by Agglutination-PCR (ADAP) assays in two laboratories were compared to single plex radiobinding assays (RBA) to define threshold levels for diagnostic specificity and sensitivity.
METHODS: IAA, GADA, IA-2A and ZnT8A were analysed in 1504 (54% females) population based controls (PBC), 456 (55% females) doctor\'s office controls (DOC) and 535 (41% females) blood donor controls (BDC) as well as in 2300 (48% females) patients newly diagnosed (1-10 years of age) with stage 3 type 1 diabetes. The thresholds for autoantibody positivity were computed in 100 10-fold cross-validations to separate patients from controls either by maximizing the χ2-statistics (chisq) or using the 98th percentile of specificity (Spec98). Mean and 95% CI for threshold, sensitivity and specificity are presented.
RESULTS: The ADAP ROC curves of the four autoantibodies showed comparable AUC in the two ADAP laboratories and were higher than RBA. Detection of two or more autoantibodies using chisq showed 0.97 (0.95, 0.99) sensitivity and 0.94 (0.91, 0.97) specificity in ADAP compared to 0.90 (0.88, 0.95) sensitivity and 0.97 (0.94, 0.98) specificity in RBA. Using Spec98, ADAP showed 0.92 (0.89, 0.95) sensitivity and 0.99 (0.98, 1.00) specificity compared to 0.89 (0.77, 0.86) sensitivity and 1.00 (0.99, 1.00) specificity in the RBA. The diagnostic sensitivity and specificity were higher in PBC compared to DOC and BDC.
CONCLUSIONS: ADAP was comparable in two laboratories, both comparable to or better than RBA, to define threshold levels for two or more autoantibodies to stage type 1 diabetes.
BACKGROUND: Supported by The Leona M. and Harry B. Helmsley Charitable Trust (grant number 2009-04078), the Swedish Foundation for Strategic Research (Dnr IRC15-0067) and the Swedish Research Council, Strategic Research Area (Dnr 2009-1039). AL was supported by the DiaUnion collaborative study, co-financed by EU Interreg ÖKS, Capital Region of Denmark, Region Skåne and the Novo Nordisk Foundation.
METHODS: IAA, GADA, IA-2A and ZnT8A were analysed in 1504 (54% females) population based controls (PBC), 456 (55% females) doctor\'s office controls (DOC) and 535 (41% females) blood donor controls (BDC) as well as in 2300 (48% females) patients newly diagnosed (1-10 years of age) with stage 3 type 1 diabetes. The thresholds for autoantibody positivity were computed in 100 10-fold cross-validations to separate patients from controls either by maximizing the χ2-statistics (chisq) or using the 98th percentile of specificity (Spec98). Mean and 95% CI for threshold, sensitivity and specificity are presented.
RESULTS: The ADAP ROC curves of the four autoantibodies showed comparable AUC in the two ADAP laboratories and were higher than RBA. Detection of two or more autoantibodies using chisq showed 0.97 (0.95, 0.99) sensitivity and 0.94 (0.91, 0.97) specificity in ADAP compared to 0.90 (0.88, 0.95) sensitivity and 0.97 (0.94, 0.98) specificity in RBA. Using Spec98, ADAP showed 0.92 (0.89, 0.95) sensitivity and 0.99 (0.98, 1.00) specificity compared to 0.89 (0.77, 0.86) sensitivity and 1.00 (0.99, 1.00) specificity in the RBA. The diagnostic sensitivity and specificity were higher in PBC compared to DOC and BDC.
CONCLUSIONS: ADAP was comparable in two laboratories, both comparable to or better than RBA, to define threshold levels for two or more autoantibodies to stage type 1 diabetes.
BACKGROUND: Supported by The Leona M. and Harry B. Helmsley Charitable Trust (grant number 2009-04078), the Swedish Foundation for Strategic Research (Dnr IRC15-0067) and the Swedish Research Council, Strategic Research Area (Dnr 2009-1039). AL was supported by the DiaUnion collaborative study, co-financed by EU Interreg ÖKS, Capital Region of Denmark, Region Skåne and the Novo Nordisk Foundation.
摘要：
背景：两种或更多种针对胰岛素（IAA）的自身抗体，谷氨酸脱羧酶（GADA），胰岛抗原-2(IA-2A)或锌转运蛋白8(ZnT8A)表示1期(血糖正常)或2期(血糖异常)1型糖尿病先于3期1型糖尿病。将两个实验室中通过凝集PCR（ADAP）测定的自动多重抗体检测与单重放射结合测定（RBA）进行比较，以定义诊断特异性和敏感性的阈值水平。
方法：IAA，GADA,IA-2A和ZnT8A在1504（54％女性）基于人群的对照（PBC）中进行了分析，456（55％女性）医生的办公室控制（DOC）和535（41％女性）献血者控制（BDC）以及2300（48％女性）新诊断的患者（1-10岁）患有3期1型糖尿病。在100次10倍交叉验证中计算了自身抗体阳性的阈值，以通过最大化χ2统计量（chisq）或使用第98百分位的特异性（Spec98）将患者与对照分开。阈值的平均值和95%CI，提出了敏感性和特异性。
结果：四种自身抗体的ADAPROC曲线在两个ADAP实验室中显示出相当的AUC，并且高于RBA。使用chisq检测两种或更多种自身抗体在ADAP中显示0.97(0.95,0.99)灵敏度和0.94(0.91,0.97)特异性,而在RBA中显示0.90(0.88,0.95)灵敏度和0.97(0.94,0.98)特异性。使用Spec98，ADAP显示0.92（0.89，0.95）的敏感性和0.99（0.98，1.00）的特异性，而RBA中的0.89（0.77，0.86）的敏感性和1.00（0.99，1.00）的特异性。与DOC和BDC相比，PBC的诊断敏感性和特异性更高。
结论：ADAP在两个实验室中具有可比性，两者都与澳洲联储相当或更好，定义两种或两种以上1型糖尿病自身抗体的阈值水平。
背景：由LeonaM.和HarryB.Helmsley慈善信托基金（授权号2009-04078）支持，瑞典战略研究基金会（DnrIRC15-0067）和瑞典研究委员会，战略研究区(Dnr2009-1039)。AL得到了DiaUnion合作研究的支持，由欧盟国际会计准则共同出资，丹麦首都地区,索恩地区和诺和诺德基金会。
方法：IAA，GADA,IA-2A和ZnT8A在1504（54％女性）基于人群的对照（PBC）中进行了分析，456（55％女性）医生的办公室控制（DOC）和535（41％女性）献血者控制（BDC）以及2300（48％女性）新诊断的患者（1-10岁）患有3期1型糖尿病。在100次10倍交叉验证中计算了自身抗体阳性的阈值，以通过最大化χ2统计量（chisq）或使用第98百分位的特异性（Spec98）将患者与对照分开。阈值的平均值和95%CI，提出了敏感性和特异性。
结果：四种自身抗体的ADAPROC曲线在两个ADAP实验室中显示出相当的AUC，并且高于RBA。使用chisq检测两种或更多种自身抗体在ADAP中显示0.97(0.95,0.99)灵敏度和0.94(0.91,0.97)特异性,而在RBA中显示0.90(0.88,0.95)灵敏度和0.97(0.94,0.98)特异性。使用Spec98，ADAP显示0.92（0.89，0.95）的敏感性和0.99（0.98，1.00）的特异性，而RBA中的0.89（0.77，0.86）的敏感性和1.00（0.99，1.00）的特异性。与DOC和BDC相比，PBC的诊断敏感性和特异性更高。
结论：ADAP在两个实验室中具有可比性，两者都与澳洲联储相当或更好，定义两种或两种以上1型糖尿病自身抗体的阈值水平。
背景：由LeonaM.和HarryB.Helmsley慈善信托基金（授权号2009-04078）支持，瑞典战略研究基金会（DnrIRC15-0067）和瑞典研究委员会，战略研究区(Dnr2009-1039)。AL得到了DiaUnion合作研究的支持，由欧盟国际会计准则共同出资，丹麦首都地区,索恩地区和诺和诺德基金会。
