Liquid Chromatography-Tandem Mass Spectrometry-Based α1-Antitrypsin (AAT) Testing

Josiah D. Murray, Maria A. Willrich, Michael J. Krowka, Aleh Bobr, David L. Murray, Kevin C. Halling, Rondell P. Graham, Melissa R. Snyder

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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 languageEnglish (US)
Pages (from-to)547-552
Number of pages6
JournalAmerican journal of clinical pathology
Issue number4
StatePublished - Apr 1 2021


  • Deficiency
  • Isoelectric focusing
  • Mass spectrometry
  • Phenotyping
  • α1-Antitrypsin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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