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Electrophoretic α1-globulin for screening of α1-antitrypsin deficient variants

  • Simone Scarlata EMAIL logo , Simona Santangelo , Ilaria Ferrarotti , Angelo Guido Corsico , Stefania Ottaviani , Panaiotis Finamore , Davide Fontana , Marc Miravitlles and Raffaele Antonelli Incalzi
Published/Copyright: April 22, 2020
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 58 Issue 11

Abstract

Background

Available screening procedures for the detection of α1-antitrypsin-deficient (AATD) mutations have suboptimal cost-effectiveness ratios. The aim in this study was to evaluate and compare the viability of a composite approach, primarily based on the α1-globulin fraction, in identifying AAT genetic analysis eligible patients against standard screening procedures, based on clinically compatible profiling and circulating AAT < 1 g/L.

Methods

A total of 21,094 subjects were screened for AATD and deemed eligible when meeting one of these criteria: α1-globulin ≤2.6%; α1-globulin 2.6%–2.9% and AST: >37 U/L and ALT: > 78 U/L; α1-globulin %: 2.9–4.6% and AST: >37 U/L and ALT: >78 U/L and erythrocyte sedimentation rate (ESR) >34 mm/h and C-reactive protein (CRP) >3 mg/L. Subjects were genotyped for the AAT gene mutation. Detection rates, including those of the rarest variants, were compared with results from standard clinical screenings. Siblings of mutated subjects were included in the study, and their results compared.

Results

Eighty-two subjects were identified. Among these, 51.2% were found to carry some Pi*M variant versus 15.9% who were clinically screened. The detection rates of the screening, including relatives, were: 50.5% for the proposed algorithm and 18.9% for the clinically-based screening. Pi*M variant prevalence in the screened population was in line with previous studies. Interestingly, 46% of subjects with Pi*M variants had an AAT plasma level above the 1 g/L threshold.

Conclusions

A composite algorithm primarily based on the α1-globulin fraction could effectively identify carriers of Pi*M gene mutation. This approach, not requiring clinical evaluation or AAT serum determination, seems suitable for clinical and epidemiological purposes.

Keywords: α1-antitrypsin; α1-globulin fraction; screening; serum electrophoresis
Corresponding author: Simone Scarlata, MD, Unit of Respiratory Pathophysiology and Thoracic Endoscopy – Geriatrics, Department of Medicine, Campus Bio-Medico University and Teaching Hospital, Via Alvaro del Portillo 200, 00128 Rome, Italy, Phone: +3906225411167, Fax: +390622541456

Acknowledgments

Authors wish to acknowledge the technical and data management support received by Katia Monnati, Eng., and Alessandra Bollettieri, Eng., at Help Desk Medarchiver board; Marco Venditti, Eng., head of the IT Operations Unit at Campus Bio Medico University and Teaching Hospital.

  1. Author contributions: SSc, SSan and RAI participated in the study concept and design; SSc, SSan, PF and DF collected the data; IF, SO and AGC were in charge of the blood sample genotyping; SSc and PF performed data analyses; SSc, SSan, PF, IF, AGC, MM and RAI reviewed the manuscript for important intellectual content. The authors fulfill authorship criteria, they revised the final version of the manuscript and consented to publication.

  2. Research funding: None declared.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: Local ethical board approval released on September 21st 2016, protocol number: 43/16 OSS ComEt CBM.

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Received: 2020-01-19
Accepted: 2020-03-23
Published Online: 2020-04-22
Published in Print: 2020-10-25

©2020 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2020-0071
Keywords for this article
α1-antitrypsin; α1-globulin fraction; screening; serum electrophoresis

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Biotin interference in cardiac troponin immunoassay – where the wild things are?
  4. Review
  5. Laboratory-related issues in the measurement of cardiac troponins with highly sensitive assays
  6. Mini Review
  7. Chromatographic methods development for clinical practice: requirements and limitations
  8. Opinion Paper
  9. Harmonising EQA schemes the next frontier: challenging the status quo
  10. Genetics and Molecular Diagnostics
  11. Direct comparison study between droplet digital PCR and a combination of allele-specific PCR, asymmetric rapid PCR and melting curve analysis for the detection of BRAF V600E mutation in plasma from melanoma patients
  12. A novel mitochondrial m.14430A>G (MT-ND6, p.W82R) variant causes complex I deficiency and mitochondrial Leigh syndrome
  13. Obesity status modifies the association between rs7556897T>C in the intergenic region SLC19A3-CCL20 and blood pressure in French children
  14. General Clinical Chemistry and Laboratory Medicine
  15. Influence of reagent lots and multiple measuring systems on estimating the coefficient of variation from quality control data; implications for uncertainty estimation and interpretation of QC results
  16. Electrophoretic α1-globulin for screening of α1-antitrypsin deficient variants
  17. A continued method performance monitoring approach for the determination of pediatric renin samples – application within a European clinical trial
  18. Pilot study for cystic fibrosis neonatal screening: the Cuban experience
  19. Validation of the analytical performance of the NOVEOS™ System, a system which improves upon the third-generation in vitro allergy testing technology
  20. IgE cross-reactivity measurement of cashew nut, hazelnut and peanut using a novel IMMULITE inhibition method
  21. Sexual dimorphism in the cerebrospinal fluid total protein content
  22. Current state of the morphological assessment of urinary erythrocytes in The Netherlands: a nation-wide questionnaire
  23. Reference Values and Biological Variations
  24. Within-subject and between-subject biological variation of first morning void urine amino acids in 12 healthy subjects
  25. Proenkephalin as a new biomarker for pediatric acute kidney injury – reference values and performance in children under one year of age
  26. Hematology and Coagulation
  27. Quality performance for indirect Xa inhibitor monitoring in patients using international external quality data
  28. Cardiovascular Diseases
  29. Clinical risk assessment of biotin interference with a high-sensitivity cardiac troponin T assay
  30. Short- and long-term biological variation of cardiac troponin I in healthy individuals, and patients with end-stage renal failure requiring haemodialysis or cardiomyopathy
  31. Infectious Diseases
  32. Monocyte distribution width (MDW) as a screening tool for sepsis in the Emergency Department
  33. Performance of a Toxo IgM prototype assay for the diagnosis of maternal and congenital Toxoplasma infections
  34. Letters to the Editors
  35. Evaluation of an ELISA for SARS-CoV-2 antibody testing: clinical performances and correlation with plaque reduction neutralization titer
  36. Preliminary evaluation of Roche Cobas Elecsys Anti-SARS-CoV-2 chemiluminescence immunoassay
  37. Hypoalbuminemia and elevated D-dimer in COVID-19 patients: a call for result harmonization
  38. Total pathway to method validation
  39. Derivation of performance specifications for uncertainty of serum C-reactive protein measurement according to the Milan model 3 (state of the art)
  40. FGF23 measurement in burosumab-treated patients: an emerging treatment may induce a new analytical interference
  41. Use of a modified IDS-ISYS intact PTH assay for intraoperative PTH measurements
  42. Agreement of dried blood spot lyso-Gb3 concentrations obtained from different laboratories in patients with Fabry disease
  43. Influence of delayed separation of plasma from whole blood and centrifugation protocol on Zn plasma concentration
  44. A survey of order of draw on inpatient wards and adherence to EFLM-COLABIOCLI recommendations
  45. Successful implementations of automated minimum re-test intervals to overcome ferritin over-requesting in a Spanish hospital laboratory
  46. Remarkable pseudoleucocytosis induced by mild cryoglobulinemia
  47. Massive hemolysis due to Clostridium perfringens: a laboratory’s perspective
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