Department of Laboratory Medicine and Pathology.
Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN.
Am J Clin Pathol. 2021 Mar 15;155(4):547-552. doi: 10.1093/ajcp/aqaa149.
Failure to produce sufficient quantities of functional α1-antitrypsin (AAT) can result in AAT deficiency (AATD) and significant comorbidities. Laboratory testing plays a vital role in AATD, with diagnosis requiring documentation of both a low AAT level and a mutated allele. This retrospective evaluation examines the efficacy of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) (proteotyping)-based algorithm for AATD detection.
A 16-month retrospective data analysis was performed on two cohorts: 5,474 samples tested with the proteotype-based algorithm and 16,147 samples directly tested by isoelectric focusing (IEF) phenotyping.
LC-MS/MS reduced the rate of IEF testing by 97%. The 3% of cases reflexed to IEF resulted in 12 (0.2%) additional phenotype findings. Retrospectively applying the proteotype-based algorithm to the IEF cohort demonstrated a 99.9% sensitivity for the detection of deficiency-associated phenotypes. Most deficiency phenotypes missed by the proteotyping algorithm would come from heterozygous patients with an F, I, or P paired to an S or Z. In all of these cases, patient AAT levels were greater than 70 mg/dL, above the threshold for AAT augmentation therapy.
The proteotype algorithm is a sensitive and cost-effective approach for the diagnosis of clinical AAT deficiency.
无法产生足够数量的功能性α1-抗胰蛋白酶（AAT）可导致 AAT 缺乏症（AATD）和严重的合并症。实验室检测在 AATD 中起着至关重要的作用，诊断需要记录 AAT 水平低和突变等位基因。本回顾性评估检查了基于液相色谱-串联质谱（LC-MS/MS）（蛋白质组学）的 AATD 检测算法的疗效。
对两个队列进行了为期 16 个月的回顾性数据分析：5474 个样本使用基于蛋白质组学的算法进行测试，16147 个样本直接通过等电聚焦（IEF）表型进行测试。
LC-MS/MS 将 IEF 检测率降低了 97%。反射到 IEF 的 3%的病例导致了 12 个（0.2%）额外的表型发现。将基于蛋白质组学的算法回溯应用于 IEF 队列，显示出检测与缺乏相关的表型的敏感性为 99.9%。大多数被蛋白质组学算法错过的缺陷表型可能来自杂合子患者，他们的 F、I 或 P 与 S 或 Z 配对。在所有这些情况下，患者的 AAT 水平大于 70mg/dL，高于 AAT 增强治疗的阈值。
蛋白质组算法是一种敏感且具有成本效益的临床 AAT 缺乏症诊断方法。
