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Quantitation of circulating wild-type alpha-1-antitrypsin in heterozygous carriers of the S and Z deficiency alleles

Overview of attention for article published in Respiratory Research, January 2015
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (75th percentile)
  • Good Attention Score compared to outputs of the same age and source (79th percentile)

Mentioned by

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5 tweeters
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1 Facebook page
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1 Google+ user
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1 research highlight platform

Citations

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7 Dimensions

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14 Mendeley
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Title
Quantitation of circulating wild-type alpha-1-antitrypsin in heterozygous carriers of the S and Z deficiency alleles
Published in
Respiratory Research, January 2015
DOI 10.1186/s12931-015-0256-9
Pubmed ID
Authors

L. J Donato, R. M Karras, J. A Katzmann, D. L Murray, M. R Snyder, L. J. Donato, R. M. Karras, J. A. Katzmann, D. L. Murray, M. R. Snyder

Abstract

Alpha-1-antitrypsin (A1AT) deficiency disease results from mutations in the A1AT gene. Controversy exists in regards to treatment of heterozygous carriers of the S and Z deficiency alleles. Quantitation of allelic expression has not been possible with standard laboratory methods. Here we show that the recently described method for liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of A1AT tryptic peptides can differentiate between mutated (S and Z) and wild-type (non-S and non-Z) proteins allowing for quantitation of circulating allelic expression in heterozygous patients. Serum (244 M/M, 61 M/Z, and 63 M/S) was combined with isotopically labeled peptide standards, digested with trypsin, and quantitated by LC-MS/MS. Total and allele-specific A1AT quantitation was performed by comparison of peptide peak height ratios to a standard curve for each peptide. Linear regression was used to compare results and central 95(th) percentile intervals were calculated using parametric analysis. Quantitation of circulating wild-type A1AT based on the proteotypic and allelic (non-S and non-Z) peptides was validated in M/M patients. Proteotypic peptide concentrations correlated linearly with quantitation by non-Z and non-S peptides [slopes (Spearman correlation coefficient) of 1.09 (0.89) and 0.98 (0.80), respectively]. Allele-specific quantitation showed significant differences in wild-type protein expression in M/Z and M/S patients. Although average total A1AT concentration was lower for M/Z patients, the percentage of wild-type protein in M/Z patients was significantly higher at 82 % (55- > 95 %) compared to 63 % (43-83 %) for M/S heterozygotes. In a cohort of M/Z patients with sufficient total A1AT (≥80 mg/dL), half had insufficient wild-type protein that could have clinical implications for pulmonary dysfunction. For the first time, a method to quantitate A1AT allele protein expression is described. Given the wide range of circulating wild-type protein observed in heterozygous patients, this method has the potential to reveal correlations between allele concentration and development and/or severity of clinical symptoms.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 14 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 7%
Canada 1 7%
Unknown 12 86%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 4 29%
Researcher 3 21%
Student > Master 2 14%
Other 1 7%
Student > Doctoral Student 1 7%
Other 2 14%
Unknown 1 7%
Readers by discipline Count As %
Agricultural and Biological Sciences 4 29%
Medicine and Dentistry 3 21%
Biochemistry, Genetics and Molecular Biology 2 14%
Nursing and Health Professions 1 7%
Psychology 1 7%
Other 2 14%
Unknown 1 7%

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 September 2015.
All research outputs
#2,355,017
of 10,677,937 outputs
Outputs from Respiratory Research
#279
of 1,236 outputs
Outputs of similar age
#56,763
of 234,940 outputs
Outputs of similar age from Respiratory Research
#9
of 43 outputs
Altmetric has tracked 10,677,937 research outputs across all sources so far. Compared to these this one has done well and is in the 77th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,236 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.0. This one has done well, scoring higher than 77% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 234,940 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 75% of its contemporaries.
We're also able to compare this research output to 43 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 79% of its contemporaries.