Abstract | OBJECTIVE: METHODS: Monoclonal ACPAs generated from plasma cells of RA patients were transferred to wild-type and PAD4-deficient mice. Pain-like behavior and macroscopic inflammation were monitored for a period of 4 weeks, followed by the analyses of tenosynovitis in the ankle joints using magnetic resonance imaging (MRI) and bone microarchitecture in the tibia using an X-ray microscope. Microscopic changes in the tendon sheath were analyzed in decalcified ankle joint sections. RESULTS: The combination of 2 monoclonal ACPAs (1325:04C03 and 1325:01B09) induced long-lasting pain-like behavior and trabecular bone loss in mice. Although no synovitis was observed macroscopically, we detected tenosynovitis in the ACPA-injected mice by MRI. Microscopic analyses of the joints revealed a cellular hyperplasia and a consequent enlargement of the tendon sheath in the ACPA-treated group. In PAD4-/- mice, the effects of ACPAs on pain-like behavior, tenosynovitis, and bone loss were significantly reduced. CONCLUSION: Monoclonal ACPAs can induce tenosynovitis in addition to pain and bone loss via mechanisms dependent on PAD4-mediated citrullination.
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Authors | Akilan Krishnamurthy, Alexandra Circiumaru, Jitong Sun, Yogan Kisten, Peter Damberg, Koji Sakuraba, Katalin Sandor, Patrik Jarvoll, Tunhe Zhou, Vivianne Malmström, Camilla I Svensson, Aase Hensvold, Anca I Catrina, Lars Klareskog, Bence Réthi |
Journal | Arthritis & rheumatology (Hoboken, N.J.)
(Arthritis Rheumatol)
Vol. 75
Issue 2
Pg. 164-170
(02 2023)
ISSN: 2326-5205 [Electronic] United States |
PMID | 35930718
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. |
Chemical References |
- acetyl 4-aminosalicylic acid
- Anti-Citrullinated Protein Antibodies
- Autoantibodies
- Protein-Arginine Deiminase Type 4
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Topics |
- Animals
- Mice
- Anti-Citrullinated Protein Antibodies
- Arthritis, Rheumatoid
- Autoantibodies
- Pain
- Tenosynovitis
(diagnostic imaging)
- Protein-Arginine Deiminase Type 4
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