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The following is a summary of “Clinical response and corresponding blood transcriptome pathways before and after treatment of hereditary angioedema prodromes compared to active swelling attacks,” published in the December 2024 issue of Allergy and Immunology by Ghosh et al.
Hereditary angioedema (HAE) attacks are often preceded by prodromal symptoms in about 85% of cases.
Researchers conducted a retrospective study to investigate the clinical effect of treating HAE C1-esterase inhibitor (HAE-C1-INH) type 1 patients with recombinant human C1-INH (rhC1-INH) during their prodrome vs an active swelling episode.
They conducted a 2-center, unblinded, case-crossover study with 5 patients with HAE-C1INH Type 1. Each patient was randomly assigned to prodrome or attack-treatment groups, receiving Conestat Alfa® (50 IU/kg body weight, max. 4200 IU for weight ≥85kg) during either 2 prodromes or 2 HAE attacks, then crossed over to the opposite treatment. Blood samples for RNAseq analysis were collected at baseline, during the prodrome before and after treatment, and during an attack before and after treatment. Differentially regulated genes and pathways were analyzed using Ingenuity Pathway Analysis (IPA, Qiagen).
The results showed that treatment with Conestat Alfa® during the HAE prodrome was as effective as treating an acute attack. Prodromes were linked to the upregulation of inflammatory extracellular matrix genes, neuropeptide, and inflammasome member genes (e.g., SPARCL1, AGRP, NLRP9; log FC = 4.1, 3.9, and 3.0, respectively). TNF-a and IL-10 were major hub genes in prodrome-associated gene networks. Conestat Alfa® reversed the disease signature in dysregulated pathways. Approximately 42% of prodrome-associated Differentially Expressed Genes (DEGs) were also linked to HAE attacks. Enriched gene networks for prodrome (ERK and VEGF) and acute attack (Insulin and SERPINA1) were identified, with shared pathways in neutrophil function and prostaglandin metabolism.
Investigators concluded that treating HAE-C1INH Type 1 patients clinically and mechanistically justified during a well-defined prodrome. This approach represented a paradigm shift in the management of HAE on-demand treatment.
Source: jacionline.org/article/S0091-6749(24)02353-4/abstract
