Proteomics

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Arthritis protection conferred by a subset of antibodies to citrullinated proteins in rheumatoid arthritis - human synovium fluids samples


ABSTRACT: Anti-citrullinated protein antibodies (ACPAs) are one of the hallmarks in rheumatoid arthritis (RA), but the in vivo function remained unclear. To investigate the effects of ACPAs, we expressed monoclonal ACPAs derived from RA patients, and analyzed the functions in mouse models, as well as the reactivity to tissue and peptides/proteins. All ACPAs showed no arthritogenicity and could not induce pain-like behavior in mice whereas one of them (E4) profoundly protected against antibody-induced arthritis. E4 showed a tissue binding pattern restricted to skin epithelial cells, to macrophages and dendritic cells in lymphoid tissue and to cartilage from mouse and human arthritic joints. Proteomic analysis showed that E4 had a distinct binding pattern to macrophage and RA synovial fluid proteins (e.g. alpha-enolase). The protective effect was epitope specific but also dependent on Fc-FCGR2B interaction on macrophages following the immune complex formation, resulting an increased IL-10 production and osteoclastogenesis reduction. The findings suggest that certain ACPAs could be protective in arthritis with therapeutic potentials.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Synovial Fluid, Synovium

DISEASE(S): Rheumatoid Arthritis

SUBMITTER: Christian Beusch  

LAB HEAD: Rikard Holmdahl

PROVIDER: PXD035180 | Pride | 2023-01-09

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
210322_Yibo_sample1.raw Raw
210322_Yibo_sample10.raw Raw
210322_Yibo_sample11.raw Raw
210322_Yibo_sample2.raw Raw
210322_Yibo_sample3.raw Raw
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