Liquid Chromatography-Tandem Mass Spectrometry-Based [alpha]1-Antitrypsin Testing: A Retrospective Evaluation of a Clinical Algorithm to Detect AAT Deficiency

Objectives: Failure to produce sufficient quantities of functional [alpha]1-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 re...

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Bibliographic Details
Published in:American journal of clinical pathology Vol. 155; no. 4; p. 547
Main Authors: Murray, Josiah D, Willrich, Maria A, Krowka, Michael J, Bobr, Aleh, Murray, David L, Halling, Kevin C, Graham, Rondell P, Snyder, Melissa R
Format: Journal Article
Language:English
Published: Oxford University Press 01.04.2021
Subjects:
Algorithms
Alpha 1-antitrypsin
Comorbidity
Gene mutations
Information management
Liquid chromatography
Mass spectrometry
ISSN:0002-9173
Online Access:Get full text
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Summary:Objectives: Failure to produce sufficient quantities of functional [alpha]1-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. Methods: 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. Results: 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 Ppaired 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. Conclusions: Theproteotype algorithm is a sensitive and cost-effective approach for the diagnosis of clinical AAT deficiency. Key Words: [alpha]1-Antitrypsin; Deficiency; Mass spectrometry; Isoelectric focusing; Phenotyping
ISSN:0002-9173
DOI:10.1093/AJCP/AQAA149