Table_1_Advances in risk predictive performance of pre-symptomatic type 1 diabetes via the multiplex Antibody-Detection-by-Agglutination-PCR assay.xlsx

IntroductionAchieving early diagnosis of pre-symptomatic type 1 diabetes is critical to reduce potentially life-threatening diabetic ketoacidosis (DKA) at symptom onset, link patients to FDA approved therapeutics that can delay disease progression and support novel interventional drugs development. The presence of two or more islet autoantibodies in pre-symptomatic type 1 diabetes patients indicates high-risk of progression to clinical manifestation.
MethodHerein, we characterized the capability of multiplex ADAP assay to predict type 1 diabetes progression. We obtained retrospective coded sera from a cohort of 48 progressors and 44 non-progressors from the NIDDK DPT-1 study.
ResultThe multiplex ADAP assay and radiobinding assays had positive predictive value (PPV)/negative predictive value (NPV) of 68%/92% and 67%/66% respectively. The improved NPV stemmed from 12 progressors tested positive for multiple islet autoantibodies by multiplex ADAP assay but not by RBA. Furthermore, 6 out of these 12 patients tested positive for multiple islet autoantibodies by RBA in subsequent sampling events with a median delay of 2.8 years compared to multiplex ADAP assay.
DiscussionIn summary, multiplex ADAP assay could be an ideal tool for type 1 diabetes risk testing due to its sample-sparing nature (4µL), non-radioactiveness, compatibility with widely available real-time qPCR instruments and favorable risk prediction capability.

引言：实现症状前1型糖尿病的早期诊断，对于降低患者症状发作时可能危及生命的糖尿病酮症酸中毒（diabetic ketoacidosis，DKA）风险、将患者纳入美国食品药品监督管理局（Food and Drug Administration，FDA）批准的可延缓疾病进展的治疗方案，以及助力新型干预药物的研发均具有重要意义。症状前1型糖尿病患者若检出2种及以上胰岛自身抗体，则提示其进展为临床显性疾病的风险较高。
方法：本研究中，我们评估了多重ADAP检测（multiplex ADAP assay）预测1型糖尿病进展的性能。我们从美国国立糖尿病、消化和肾脏疾病研究所（National Institute of Diabetes and Digestive and Kidney Diseases，NIDDK）的DPT-1研究队列中，获取了48名进展者与44名非进展者的回顾性编码血清样本。
结果：多重ADAP检测与放射结合检测（radiobinding assays，RBA）的阳性预测值（positive predictive value，PPV）/阴性预测值（negative predictive value，NPV）分别为68%/92%与67%/66%。该检测的阴性预测值得以提升，源于12名进展者经多重ADAP检测呈多种胰岛自身抗体阳性，但放射结合检测结果为阴性。此外，上述12名患者中有6名在后续采样中经放射结合检测呈多种胰岛自身抗体阳性，相较于多重ADAP检测的采样时间，中位延迟时长为2.8年。
讨论：综上，多重ADAP检测凭借其样本需求量低（仅需4微升）、无放射性、可兼容市面广泛使用的实时定量聚合酶链式反应（real-time quantitative polymerase chain reaction，qPCR）仪器，以及优异的风险预测性能，有望成为1型糖尿病风险检测的理想工具。