A new study has found a significant overlap in gene and pathway levels between hereditary angioedema (HAE) prodromes and attacks. The study, published in the Journal of Allergy and Clinical Immunology, suggests that the use of a treatment such as recombinant C1 esterase inhibitor (Ruconest®) may be justified to prevent the progression of the prodrome to an acute HAE attack.
The results will be presented at the 2023 American Academy of Allergy, Asthma and Immunology (AAAAI) Annual Meeting taking place February 24 to 27, 2023, in San Antonio, Texas.
“Hereditary angioedema (HAE) attacks are associated with a prodrome in ∼85% of patients’ pre-attack,” the authors wrote. “The purpose of this study was to determine whether blood transcriptomic changes, pre- and post-treatment of a prodrome with Ruconest (recombinant human [C1 inhibitor]), overlapped with changes pre- and post-treatment of an acute attack.”
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HAE is a rare disease characterized by repeated episodes of acute and debilitating swelling in the face, limbs, gastrointestinal tract, and airway. Attacks can be triggered by minor trauma or stress, or they can appear without apparent cause. HAE is caused by a deficiency or dysfunction of C1 inhibitor due to mutations in the SERPING1 gene, and it is inherited in an autosomal dominant manner.
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The research team conducted a multicenter, unblinded, case-crossover study on 5 patients with HAE attacks who were assigned to 2 groups: prodrome or attack treatment. After 2 prodromes or 2 attacks, the patients switched groups and the results were compared.
All patients were treated with recombinant C1 esterase inhibitor during either the prodrome or the attack, and blood samples were obtained at baseline and before and after the prodrome or attack. RNA sequencing was employed to assess differentially regulated genes and pathways.
The results revealed that multiple inflammatory genes were upregulated during HAE prodromes, and treatment with recombinant C1 esterase inhibitor led to the reversal of the dysregulated HAE-associated pathways.
Some 42% of the differentially associated genes in the prodrome were also associated with acute attacks, suggesting common hub genes and shared gene networks between attacks and the HAE prodrome.
Reference
Ghosh D, Singh U, Anderson J, Bernstein J. Biologic pathways involved in hereditary angioedema and response to Ruconest® treatment during prodrome and attack. J Allergy Clin Immunol. 2023;151(2):AB340. doi:10.1016/j.jaci.2022.12.796
