C-reactive protein measurement may not be necessary to diagnose alpha-1 antitrypsin deficiency (AATD) if patients are evaluated for alpha-1 antitrypsin (AAT) levels and undergo genotyping at the same time, according to a prospective observational analytic study published in the Clinical Respiratory Journal.

For many years, it has been suggested to measure C-reactive protein levels in patients being tested for AATD for a correct interpretation of AAT levels, as it is of paramount importance to determine if there are any underlying inflammatory conditions altering AAT levels.

AAT is an acute phase reactant primarily synthesized by the liver due to several triggers, ranging from infectious to inflammatory in nature. Likewise, AAT levels also vary with the different genotypes causing AATD.

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The main reason behind C-reactive protein characterization before measuring AAT levels is the possible alterations of these levels by an underlying pathology stimulating acute phase reactants in general, including AAT. These AAT values can widely vary, even within the same AATD genotype.

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The authors carried out the study on 1510 patients attending the outpatient pulmonology clinic for any cause. Most of these patients (80%) were stable, while the rest had an acute exacerbation of the disease. Then, they performed both genotyping and measurement of AAT levels at the same time without measuring C-reactive protein levels. 34

The median AAT value was 123.5 mg/dL with a standard deviation of 31.8. The diagnosis success of deficient variants was 31.4%, detecting both common and rare variants. 

“The results showed that the measurement of the AAT levels together with the performance of the genotyping in the same act avoided errors and made it unnecessary to obtain the [C-reactive protein],” the authors said. “Since it did not matter if the AAT values were increased due to inflammation, infection, or for another reason, since when carrying out the joint genotype, the diagnosis was reached safely, quickly, and efficiently.”

Moreover, when analyzing the data, the authors noted that existing variations in AAT levels were minimal, especially in the lower limit for each genotype. Regarding the benefits, not performing C-reactive protein measurements could avoid unnecessary visits and inconveniences for patients, like repeat extractions.

“The AAT levels obtained for each genotype were divided according to whether or not the patient had an exacerbation, confirming that in a stable situation, prior measurement of [C-reactive protein] levels is not necessary,” the authors concluded.


Hernández‐Pérez JM, López‐Charry CV. Is the determination of C‐reactive protein really necessary in the diagnosis of alpha‐1 antitrypsin deficiency? Clin Respir J. Published online May 17, 2022. doi:10.1111/crj.13494