Unveiling signaling pathways inducing MHC class II expression in neutrophils.

Introduction: Gram-negative bacillary bacteremia poses a significant threat, ranking among the most severe infectious diseases capable of triggering life-threatening sepsis. Despite the unambiguous involvement of neutrophils in this potentially fatal disease, there are limited data about the molecular signaling mechanisms, phenotype, and function of human neutrophils during the early phase of gram-negative bacillary bacteremia.

Methods: By using an unbiased proteomics and flow cytometry approach, we identified an antigen-presenting cell (APC)-like phenotype in human peripheral blood neutrophils (PMN) with MHC class II molecule expression in the early phase of bacteremia.

Secukinumab in Pediatric Patients with Plaque Psoriasis: Pooled Safety Analysis from Two Phase 3 Randomized Clinical Trials.

Background: Plaque psoriasis affects ~ 1% of the pediatric population, negatively impacting quality of life. The efficacy and safety of secukinumab in pediatric patients with moderate to severe or severe chronic plaque psoriasis have been established in two pivotal phase 3 trials (open-label, NCT03668613; double-blind, NCT02471144).

Objectives: The aims were to report the pooled safety of secukinumab up to 52 weeks from two studies in subgroups of pediatric patients stratified by age and bodyweight, and to present, alongside the pediatric data, the pooled safety data from four pivotal adult secukinumab trials.

Efficacy of Secukinumab Across Subgroups and Overall Safety in Pediatric Patients with Moderate to Severe Plaque Psoriasis: Week 52 Results from a Phase III Randomized Study.

Background: The efficacy and safety of biologic treatments for children and adolescents with moderate to severe psoriasis should be examined over a considerable time period and in different subgroups.

Objective: We report the efficacy and safety of secukinumab low dose (LD) and high dose (HD) regimens in pediatric patients with moderate to severe psoriasis for up to Week 52.

Methods: This was a randomized, open-label, parallel-group, multicenter study in patients aged  6 to < 18 years.

Thermostable designed ankyrin repeat proteins (DARPins) as building blocks for innovative drugs.

Designed ankyrin repeat proteins (DARPins) are antibody mimetics with high and mostly unexplored potential in drug development. By using in silico analysis and a rationally guided Ala scanning, we identified position 17 of the N-terminal capping repeat to play a key role in overall protein thermostability. The melting temperature of a DARPin domain with a single full-consensus internal repeat was increased by 8 °C to 10 °C when Asp17 was replaced by Leu, Val, Ile, Met, Ala, or Thr.