Therapeutic ACPA inhibits NET formation: a potential therapy for neutrophil-mediated inflammatory diseases.

ABSTRACT: Excessive release of neutrophil extracellular traps (NETs) is associated with disease severity and contributes to tissue injury, followed by severe organ damage. Pharmacological or genetic inhibition of NET release reduces pathology in multiple inflammatory disease models, indicating that NETs are potential therapeutic targets. Here, we demonstrate using a preclinical basket approach that our therapeutic anti-citrullinated protein antibody (tACPA) has broad therapeutic potential. Treatment with tACPA prevents disease symptoms in various mouse models with plausible NET-mediated pathology, including inflammatory arthritis (IA), pulmonary fibrosis, inflammatory bowel disease and sepsis. We show that citrulline residues in the N-termini of histones 2A and 4 are specific targets for therapeutic

SUBMITTER: Chirivi RGS 

PROVIDER: S-EPMC8166830 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature