Comparison of different algorithms in laboratory diagnosis of alpha1-antitrypsin deficiency

Balderacchi, Alice Maria; Barzon, Valentina; Ottaviani, Stefania; Corino, Alessandra; Zorzetto, Michele; Wencker, Marion; Corsico, Angelo Guido; Ferrarotti, Ilaria

doi:10.1515/cclm-2020-1881

Cited by 17 publications

(13 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We carried out a retrospective review of our diagnostic phenotyping results from March 2014 to January 2019 in all samples carrying the M wurzburg allele (76 out of 5916) as revealed by exon 5 sequencing of the SERPINA1 gene, which was performed according to the recently described diagnostic algorithm [ 6 ]. Direct comparison identified a particular electrophoretic pattern amenable to the M wurzburg protein.…”

Section: Resultsmentioning

confidence: 99%

“…Subsequently, we selected 18 patients displaying the M wurzburg, IEF pattern from all samples in our archives that had not been sequenced using the current diagnostic algorithm [ 6 ], mainly because AAT concentrations were above the decisional cut-off values. We then checked them for the presence of the M wurzburg allele by sequencing exon 5 of the SERPINA1 gene ( Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…To date, there is no universally-established algorithm used by laboratories for the detection of AATD patients. The algorithms applied in different countries depend on diverse criteria based on the availability of diagnostic facilities and expertise, country-specific indications, and the occurrence of variants [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Improving the Laboratory Diagnosis of M-like Variants Related to Alpha1-Antitrypsin Deficiency

Barzon

Ottaviani

Balderacchi

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

Alpha1-antitrypsin (AAT) is a serine protease inhibitor that is encoded by the highly polymorphic SERPINA1 gene. Mutations in this gene can lead to AAT deficiency (AATD), which is associated with an increased risk of lung and/or liver disease. On the basis of electrophoretic migration, AAT variants are named with capital letters; M (medium) signifies the normal protein. Among pathological variants, the M-like ones represent a heterogeneous group of rare allelic variants that exhibit the same electrophoretic pattern as the M wild-type protein, which makes them difficult to detect with routine methods. In order to avoid their misdiagnosis, the present study defines and validates effective methods for the detection of two pathogenic M-like variants, Mwurzburg and Mwhitstable. Comparison of protein phenotypes using isoelectric focusing of samples that presented the Mwurzburg variant, as revealed by exons 5 sequencing, identified a particular electrophoretic pattern amenable to the Mwurzburg protein. The specific phenotyping pattern was retrospectively validated, thus enabling the detection of 16 patients with Mwurzburg variant among the subjects already tested but not sequenced according to our diagnostic algorithm. The Mwhitstable allele was detected by intron 4 sequencing of SERPINA1 gene. Mwurzburg and Mwhitstable are often misdiagnosed and the introduction of diagnostic improvements can help the clinical management, especially in patients with established lung disease without any other reported risk factors.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Improving the Laboratory Diagnosis of M-like Variants Related to Alpha1-Antitrypsin Deficiency

Barzon

Ottaviani

Balderacchi

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Even though AATD is the most frequent genetic lung disease in the Caucasian population, it remains underdiagnosed and only a modest proportion of patients are detected with this condition. 18 The relevance of early diagnosis, pre or neonatally, has been a matter of discussion. Even though it is acknowledged that early identification of AATD enables those individuals to implement preventive therapeutic or lifestyle measures which may protect lung and/or liver damage, thus delaying the onset of disease, some ethical concerns may be raised.…”

Section: Expert Perspectives Pre or Neonatal Diagnosis Of Aatdmentioning

confidence: 99%

Expert Perspectives on the Management of Alpha 1-Antitrypsin Deficiency

et al. 2022

View full text Add to dashboard Cite

Alpha 1-antitrypsin deficiency is an inherited autosomal codominant disorder, which predisposes patients to lung and/or liver disease. Even though it is considered rare, it is one of the most frequent genetic disorders worldwide, albeit remaining underdiagnosed. Several organizations and societies, including the Portuguese Society of Pulmonology have been elaborating guidelines and recommendations for the diagnosis and management of alpha 1-antitrypsin deficiency. Nevertheless, some important matters are yet to be included in those, mainly due to lack of robust scientific evidence, and continue to represent a point of discussion. This article reviews some important scientific publications and expresses the perspectives of a group of Portuguese experts regarding the management of alpha 1-antitrypsin deficiency, namely in terms of the pre and neonatal diagnosis, the impact of the COVID-19 pandemic, the validity of replacement therapy in lung transplant-receiving, and finally, alternative strategies of alpha 1-antitrypsin deficiency treatment to improve the patients’ quality of life.

show abstract

“…At present, there are numerous algorithms for the identification of AATD. Although these algorithms have some variability, most of them perform a determination of AAT in peripheral blood at some point during the diagnostic process [ 6 , 7 ]. Interestingly, the determination of AAT in peripheral blood has some technical conditions that are relevant when interpreting the results well.…”

Section: Introductionmentioning

confidence: 99%

Methodologies for the Determination of Blood Alpha1 Antitrypsin Levels: A Systematic Review

Ruiz-Duque

Bañuls

Reinoso-Arija

et al. 2021

JCM

View full text Add to dashboard Cite

Background: The study of hematic concentrations of alpha1 antitrypsin (AAT) is currently one step in the diagnosis of AAT deficiency. To try to clarify the relevance of the laboratory techniques, we carried out a systematic review of the literature. Methods: Studies evaluating the quantification of AAT in peripheral blood were searched in PubMed in July 2021. The selection criteria included (1) any type of study design that included a quantification of AAT in peripheral blood; (2) studies written in English or Spanish; (3) studies evaluating human beings; and (4) studies involving adults. Results: Out of 207 studies, the most frequently used techniques were nephelometry (43.9%), followed by ELISA (19.8%) and turbidimetry (13.5%). Altogether, 182 (87.9%) cases expressed their results in units of gram, while 16 (7.7%) articles expressed them in units of mole. Only 2.9% articles referred to the standard used, 43.5% articles indicated the commercial kit used, and 36.2% indicated the analyzer used. Conclusions: The technical aspects of these determinations are not always reported in the literature. Journals should be attentive to these technical requirements and ensure that they are included in the works in which AAT is determined in order to ensure a correct interpretation of the study findings.

show abstract

Comparison of different algorithms in laboratory diagnosis of alpha1-antitrypsin deficiency

Cited by 17 publications

References 33 publications

Improving the Laboratory Diagnosis of M-like Variants Related to Alpha1-Antitrypsin Deficiency

Improving the Laboratory Diagnosis of M-like Variants Related to Alpha1-Antitrypsin Deficiency

Expert Perspectives on the Management of Alpha 1-Antitrypsin Deficiency

Methodologies for the Determination of Blood Alpha1 Antitrypsin Levels: A Systematic Review

Contact Info

Product

Resources

About