Purpose: Alpha-1-antitrypsin deficiency (AATD) is a rare hereditary condition resulting from the mutations in the SERPINA1 (serine protease inhibitor) gene and is characterized by low circulating levels of the alpha-1 antitrypsin (AAT) protein. The traditional algorithm for laboratory testing of AATD involves the analysis of AAT concentrations (nephelometry), phenotyping (isoelectric focusing, IEF), and genotyping (polymerase chain reaction, PCR); in selected cases, full sequencing of the SERPINA1 gene can be undertaken. New technologies arise that may make diagnosis easier and faster. Methods: We developed and evaluated a new diagnostic algorithm based on Luminex xMAP (multi-analyte profiling) technology using Progenika A1AT Genotyping Test. In an initial learning phase, 1979 samples from individuals suspected of having AATD were examined by both, a traditional and a "new" algorithm. In a second phase, 1133 samples were analyzed with the Luminex xMAP only. Results: By introducing a Luminex xMAP based algorithm, we were able to simultaneously identify 14 mutations in SERPINA1 gene (instead of two- S and Z-by using our old algorithm). Although the quantity of IEF assays remained unchanged, the nephelometric measurements and sequencing were reduced by 79% and 63.4%, respectively. Conclusion: The new method is convenient, fast and user-friendly. The application of the Luminex xMAP technology can simplify and shorten the diagnostic workup of patients with suspected AATD.
- Veith, M.
- Klemmer, A.
- Anton, I.
- El Hamss, R.
- Rapun, N.
- Janciauskiene, S.
- Kotke, V.
- Herr, C.
- Bals, R.
- Vogelmeier, C. F.
- Greulich, T.
Keywords
- *Luminex xMAP technology
- *serpina1
- *diagnosis
- *mutations
- grants from Grifols, outside the submitted work. Iker Anton, Rachid El Hamss, and
- Noelia Rapun are employees of Progenika Biopharma-Grifols. Viktor Kotke reports
- grants from Grifols, outside the submitted work. Dr. Robert Bals reports grants,
- personal fees from CSL Behring and Grifols, grants from Boehinger Ingelheim and
- Novartis, during the conduct of the study. Claus Franz Vogelmeier reports grants,
- personal fees from AstraZeneca, GlaxoSmithKline, Grifols, Novartis, and
- Boehringer Ingelheim, personal fees from CSL Behring, Menarini, Mundipharma,
- Teva, Cipla, Nuvaira, and Chiesi, grants from Bayer Schering Pharma AG, MSD, and
- Pfizer, outside the submitted work. Timm Greulich reports grants from Grifols,
- during the conduct of the study
- personal fees from AstraZeneca, Berlin-Chemie,
- Boehringer-Ingelheim, Chiesi, CSL-Behring, Grifols, GSK, and Novartis, outside
- the submitted work. The authors report no other conflicts of interest in this
- work.
