Cyclic Citrullinated Peptide Aptamer Treatment Attenuates Collagen-Induced Arthritis.

Autor: Khatri S; Department of Chemistry, Technical University of Denmark, Kgs Lyngby 2800, Denmark., Hansen J; Department of Chemistry, Technical University of Denmark, Kgs Lyngby 2800, Denmark., Pedersen NB; Department of Chemistry, Technical University of Denmark, Kgs Lyngby 2800, Denmark., Brandt-Clausen IP; DTU Biofacility, Technical University of Denmark, Kgs Lyngby 2800, Denmark., Gram-Nielsen S; DTU Biofacility, Technical University of Denmark, Kgs Lyngby 2800, Denmark., Mendes AC; DTU FOOD, Technical University of Denmark, Kgs Lyngby 2800, Denmark., Chronakis IS; DTU FOOD, Technical University of Denmark, Kgs Lyngby 2800, Denmark., Keiding UB; Center for Nanomedicine and Theranostics, Department of Chemistry, Technical University of Denmark, Kgs Lyngby 2800, Denmark., Catrina AI; Department of Medicine/Solna, Division of Rheumatology, Karolinska Institute and Karolinska University Hospital, Stockholm 164 90, Sweden., Rethi B; Department of Medicine/Solna, Division of Rheumatology, Karolinska Institute and Karolinska University Hospital, Stockholm 164 90, Sweden., Clausen MH; IBIO TECH ApS, Copenhagen 2450, Denmark.; Center for Nanomedicine and Theranostics, Department of Chemistry, Technical University of Denmark, Kgs Lyngby 2800, Denmark., Kragstrup T; IBIO TECH ApS, Copenhagen 2450, Denmark.; Department of Biomedicine, University of Aarhus, Aarhus C 8000, Denmark., Astakhova K; Department of Chemistry, Technical University of Denmark, Kgs Lyngby 2800, Denmark.; IBIO TECH ApS, Copenhagen 2450, Denmark.
Jazyk: angličtina
Zdroj: Biomacromolecules [Biomacromolecules] 2022 May 09; Vol. 23 (5), pp. 2126-2137. Date of Electronic Publication: 2022 Apr 19.
DOI: 10.1021/acs.biomac.2c00144
Abstrakt: We describe the study of a novel aptamer-based candidate for treatment of seropositive rheumatoid arthritis. The candidate is a nanoparticle-formulated cyclic citrullinated peptide aptamer, which targets autoantibodies and/or the immune reactions leading to antibody production. Due to its specificity, the peptide aptamer nanoparticles might not interfere with normal immune functions as seen with other disease-modifying antirheumatic drugs. Over a 3-week course of treatment, joint swelling and arthritis score in collagen-induced rats were significantly decreased compared with animals treated with phosphate-buffered saline, unloaded nanoparticles, or nanoparticles with a noncitrullinated control peptide. The reduction in joint swelling was associated with decreased anticitrullinated peptide autoantibody levels in the blood. Treatment with aptamer nanoparticles also increased interleukin-10 levels. The effect seen with the proposed treatment candidate could be mediated by upregulation of anti-inflammatory mediators and decreased levels of anticitrullinated peptide antibodies.
Databáze: MEDLINE