How is DAAT serum concentration determined?
Determination of serum alpha-1 antitrypsin (AAT) concentration is usually the first step in investigating alpha-1 antitrypsin (AATD) deficiency.
The authors of this article analyze the reproducibility of their measurement to assess whether the variability between measurements was associated with markers or reactants of the acute phase of inflammation.
To do this, they retrospectively analyzed a sample of 255 individuals with chronic obstructive pulmonary disease (COPD) whose serum AAT levels were determined twice, at separate visits
White blood cell count and fibrinogen as markers of inflammation in the acute phase were also measured in the second determination.
In patients with severe AATD, the observed variation in AAT levels from measurement to measurement is unlikely to alter the conclusions.
The situation is less clear in patients with intermediate DAAT, in whom borderline and even normal AAT levels are often found.
They finally concluded that although the 2 serum AAT levels were significantly correlated, the agreement was weak with wide limits on AAT concentrations.
Considering that serum concentrations of AAT below 1.13 g/L justify the initiation of further investigations to confirm DAAT, discrepancies between test-retest AAT levels led to reevaluation of 22% of patients wrongly classified.
This is not an assumption, considering that many studies have shown that the MZ and SZ genotypes confer a significantly increased risk of COPD in smokers.
Serum concentration variation
AAT is synthesized and secreted primarily by hepatocytes (≥80%), and in additional amounts by monocytes, macrophages, alpha and delta cells of the pancreas, type II alveolar epithelial cells of the lung, enterocytes, and other cells.
Being an acute phase reactant, plasma concentrations of AAT increase rapidly 2-3 times in response to inflammatory or infectious stimuli, accompanying C-reactive protein (CRP) and amyloid A, and this increase is maintained from 7- 15 days.
For this reason, the determination of the serum concentration of AAT will be carried out under basal conditions and it is advisable to measure the CRP.
Therefore, the importance of accurate determination of serum AAT concentration for COPD risk stratification, as well as for counseling purposes, even in intermediate deficiency, is clear.
Concordance in AAT level has relevance to the underlying genotype: the proportion of patients carrying 1 or 2 deficiency alleles was higher in those with 2 concordant AAT levels <1.13 g/l compared with those with discordant results .
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