Abstract
Objectives: 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. 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 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. Conclusions: The proteotype algorithm is a sensitive and cost-effective approach for the diagnosis of clinical AAT deficiency.
Original language | English (US) |
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Pages (from-to) | 547-552 |
Number of pages | 6 |
Journal | American journal of clinical pathology |
Volume | 155 |
Issue number | 4 |
DOIs | |
State | Published - Apr 1 2021 |
Keywords
- Deficiency
- Isoelectric focusing
- Mass spectrometry
- Phenotyping
- α1-Antitrypsin
ASJC Scopus subject areas
- Pathology and Forensic Medicine