A subset of antibodies targeting citrullinated proteins confers protection from rheumatoid arthritis
Year: 2023
Type: article
Abstract: Although elevated levels of anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA), the in vivo functions of these antibodies remain unclear. Here, we have expressed monoclonal ACPAs derived from patients with RA, and analyzed their functions in mice, as well as their specificities. None of the ACPAs showed arthritogenicity nor induced pain-associated behavior in mice. However, one of the antibodies, clone E4, protected mice from antibody-induced arthritis. E4 showed a binding pattern restricted to skin, macrophages and dendritic cells in lymphoid tissue, and cartilage derived from mouse and human arthritic joints. Proteomic analysis confirmed that E4 strongly binds to macrophages and certain RA synovial fluid proteins such as α-enolase. The protective effect of E4 was epitope-specific and dependent on the interaction between E4-citrullinated α-enolase immune complexes with FCGR2B on macrophages, resulting in increased IL-10 secretion and reduced osteoclastogenesis. These findings suggest that a subset of ACPAs have therapeutic potential in RA.
Source: Nature Communications
Authors: Yibo He, Changrong Ge, Àlex Moreno-Giró, Bingze Xu, Christian M. Beusch, Katalin Sandor, Jie Su, Lei Cheng, Erik Lönnblom, Christina Lundqvist, Linda M. Slot, Dongmei Tong, Vilma Urbonaviciute, Bibo Liang, Taotao Li, Gonzalo Fernandez Lahore, Mike Aoun, Vivianne Malmström, Theo Rispens, Patrik Ernfors, Camilla I. Svensson, Hans Ulrich Scherer, René E. M. Toes, Inger Gjertsson, Olov Ekwall, Roman A. Zubarev, Rikard Holmdahl
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,290
OpenAlex ID: W4319593293