N-glycosylation in the SERPIN domain of C1-Esterase Inhibitor in hereditary angioedema.

Hereditary angioedema is an autosomal dominant disorder caused by defects in C1-esterase inhibitor (C1-INH), resulting in poorly controlled activation of the kallikrein-kinin system and bradykinin overproduction. C1-INH is a heavily glycosylated protein in the serine protease inhibitor (SERPIN) family, yet the role of these glycosylation sites remains unclear. To elucidate the functional impact of N-glycosylation in the SERPIN domain of C1-INH, we engineered four sets consisting of 26 variants at or near the N-linked sequon (NXS/T).

On-demand treatment of hereditary angioedema attacks: Patient-reported utilization, barriers, and outcomes.

Background: Hereditary angioedema (HAE) is clinically characterized by recurrent attacks of subcutaneous and submucosal swelling.

Objective: To investigate real-world timing, potential barriers, and impact of delaying on-demand treatment (OD) of HAE attacks.

Methods: Patients with HAE (type I or II) aged 12 years or older with more than or equal to 1 treated (Treated Cohort) or untreated (Untreated Cohort) attack in the past 3 months were recruited by the US HAE Association.

Benralizumab in children with severe eosinophilic asthma: Pharmacokinetics and long-term safety (TATE study).

Background: Benralizumab is an anti-interleukin-5 receptor α monoclonal antibody approved as an add-on maintenance treatment for patients with uncontrolled severe asthma. Prior Phase 3 studies have evaluated benralizumab in patients aged ≥12 years with severe uncontrolled asthma. The TATE study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), and safety of benralizumab treatment in children.

Immunoglobulin replacement products protect against SARS-CoV-2 infection in vivo despite poor neutralizing activity.

Immunoglobulin (IG) replacement products are used routinely in patients with immune deficiency and other immune dysregulation disorders who have poor responses to vaccination and require passive immunity conferred by commercial antibody products. The binding, neutralizing, and protective activity of intravenously administered IG against SARS-CoV-2 emerging variants remains unknown. Here, we tested 198 different IG products manufactured from December 2019 to August 2022.