New flow cytometry-based immunoassays are an easy, specific, and sensitive method of diagnosing hereditary angioedema (HAE), according to an abstract published in a special issue of the Journal of Allergy and Clinical Immunology.

The research is being presented at the 2023 American Academy of Allergy, Asthma, and Immunology (AAAAI) annual meeting that will take place in San Antonio, Texas, from February 24 to 27.

The study authors developed novel flow cytometry-based immunoassays using biotinylated factor XIIa, kallikrein, or C1-esterase (C1s) bound to streptavidin-coated microbeads.

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For the experiment, they collected plasma samples from 37 patients with HAE type 1 or 2 patients and healthy controls.

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The researchers developed standard curves for the quantification of C1-INH and used serial dilutions of normal plasma to validate the experimental assays’ ability to detect a known concentration of C1-INH. After that, they measured the functional C1-INH (fC1-INH) levels in all plasma samples and compared the obtained values with the results from a commercial lab and ELISA-based assays.

According to the results, the level of fC1-INH in all plasma samples of people with HAE was less than 40% of the normal values. Similar results could be obtained by measuring factor XIIa–C1-INH, kallikrein–C1-INH, or C1s-C1-INH complexes by all 3 assays.

By contrast, results obtained from a commercial lab revealed equivocal (41%-67%) or normal (>67%) levels of fC1-INH in 6 out of 37 tested samples.

“Specific and sensitive methods to quantitate fC1-INH are required for accurate and timely diagnosis of HAE,” Joseph and colleagues wrote. “Two commercially available assays either measure residual C1s activity or a complex ELISA measuring activated C1s. More physiologically relevant alternative methods measuring functional binding of Factor XIIa or kallikrein have been reported but they are not commercially available.”

HAE types 1 and 2 are caused by a deficiency of fC1-INH, resulting in an overproduction of bradykinin.


Joseph K, Tholanikunnel B, Yu J, et al. Flow cytometry-based immunoassays for determining functional levels of plasma protease C1 inhibitor for the diagnosis of hereditary angioedema (HAE). J Allergy Clin Immunol. Published online February 3. 2023. doi:10.1016/j.jaci.2022.12.415