Cyclic Citrullinated Peptide Aptamer Treatment Attenuates Collagen-Induced Arthritis

Sangita Khatri; Jonas Hansen; Nadia Bom Pedersen; Idamarie Palsbom Brandt-Clausen; Sanne Gram-Nielsen; Ana C. Mendes; Ioannis S. Chronakis; Ulrik Bering Keiding; Anca I. Catrina; Bence Rethi; Mads Hartvig Clausen; Tue Kragstrup; Kira Astakhova

doi:10.1021/acs.biomac.2c00144

Cyclic Citrullinated Peptide Aptamer Treatment Attenuates Collagen-Induced Arthritis

Sangita Khatri, Jonas Hansen, Nadia Bom Pedersen, Idamarie Palsbom Brandt-Clausen, Sanne Gram-Nielsen, Ana C. Mendes, Ioannis S. Chronakis, Ulrik Bering Keiding, Anca I. Catrina, Bence Rethi, Mads Hartvig Clausen, Tue Kragstrup, Kira Astakhova^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

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.

Original language	English
Journal	Biomacromolecules
Volume	23
Issue number	5
Pages (from-to)	2126-2137
Number of pages	12
ISSN	1525-7797
DOIs	https://doi.org/10.1021/acs.biomac.2c00144
Publication status	Published - 2022

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Khatri, S., Hansen, J., Pedersen, N. B., Brandt-Clausen, I. P., Gram-Nielsen, S., Mendes, A. C., Chronakis, I. S., Keiding, U. B., Catrina, A. I., Rethi, B., Clausen, M. H., Kragstrup, T., & Astakhova, K. (2022). Cyclic Citrullinated Peptide Aptamer Treatment Attenuates Collagen-Induced Arthritis. Biomacromolecules, 23(5), 2126-2137. https://doi.org/10.1021/acs.biomac.2c00144

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title = "Cyclic Citrullinated Peptide Aptamer Treatment Attenuates Collagen-Induced Arthritis",

abstract = "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.",

author = "Sangita Khatri and Jonas Hansen and Pedersen, {Nadia Bom} and Brandt-Clausen, {Idamarie Palsbom} and Sanne Gram-Nielsen and Mendes, {Ana C.} and Chronakis, {Ioannis S.} and Keiding, {Ulrik Bering} and Catrina, {Anca I.} and Bence Rethi and Clausen, {Mads Hartvig} and Tue Kragstrup and Kira Astakhova",

year = "2022",

doi = "10.1021/acs.biomac.2c00144",

language = "English",

volume = "23",

pages = "2126--2137",

journal = "Biomacromolecules",

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T1 - Cyclic Citrullinated Peptide Aptamer Treatment Attenuates Collagen-Induced Arthritis

AU - Khatri, Sangita

AU - Hansen, Jonas

AU - Pedersen, Nadia Bom

AU - Brandt-Clausen, Idamarie Palsbom

AU - Gram-Nielsen, Sanne

AU - Mendes, Ana C.

AU - Chronakis, Ioannis S.

AU - Keiding, Ulrik Bering

AU - Catrina, Anca I.

AU - Rethi, Bence

AU - Clausen, Mads Hartvig

AU - Kragstrup, Tue

AU - Astakhova, Kira

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

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DO - 10.1021/acs.biomac.2c00144

M3 - Journal article

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SN - 1525-7797

VL - 23

SP - 2126

EP - 2137

JO - Biomacromolecules

JF - Biomacromolecules

IS - 5

ER -

Cyclic Citrullinated Peptide Aptamer Treatment Attenuates Collagen-Induced Arthritis

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