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- W3097945493 abstract "Background: The Z mutation in alpha-antitrypsin (AAT) results in formation of polymeric chains within hepatocytes, with consequent reduction of AAT plasma levels and predisposition to emphysema. A small fraction of Z AAT polymers is also present in the circulation and in tissues, where it further decreases AAT anti-protease activity and may exert pro-inflammatory functions, thus contributing to the pathogenesis of lung disease in AAT deficiency (AATD). As circulating polymers are mainly secreted by the liver, their concentration in the plasma may reflect the extent of polymer accumulation in hepatocytes and the severity of associated liver diseases. Objectives: Quantification of plasma AAT polymers is a relevant diagnostic and prognostic biomarker in AATD. As most diagnostic flowcharts are performed on dried blood spots (DBS), we have standardized a method for accurate quantification of AAT polymers on DBS. Methods: We collected DBS from 20 AATD patients (10 PI*MZ and 10 PI*ZZ) and quantified AAT polymers on DBS eluates by a sandwich ELISA based on the polymer-specific 2C1 mAb for capture and an HRP-conjugated anti-AAT polyclonal for detection. Heat-induced polymers of plasma purified AAT were used as standards. Results: Polymer concentrations determined on DBS from PI*MZ (0,2±0,1 mg/dL) and PI*ZZ (1.1±0,7 mg/dL) subjects were comparable to the levels measured on matched plasma samples. Conclusions: We developed an assay that determines AAT polymer concentrations in DBS specimens. This assay will give the opportunity to test a high number of cases for plasma polymer content and thereby to evaluate the correlation of this parameter with individual lung and liver clinical manifestations of AATD." @default.
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- W3097945493 date "2020-09-07" @default.
- W3097945493 modified "2023-10-14" @default.
- W3097945493 title "Quantification of circulating alpha-1-antitrypsin polymers in dried blood spots" @default.
- W3097945493 doi "https://doi.org/10.1183/13993003.congress-2020.326" @default.
- W3097945493 hasPublicationYear "2020" @default.
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