Carbamylation is a type of posttranslational modification to proteins. More than 40 percent of patients with rheumatoid arthritis (RA) develop autoantibodies against carbamylated proteins in their plasma and synovial fluid, which increases the risk of bone erosion and mortality. In this study, the authors reported that neutrophil extracellular traps (NETs), net-like structures released by neutrophils, are the source of different autoantigens in RA and promote bone erosion and the formation of osteoclasts—the cells that degrade bone tissue. They also demonstrated that through toll-like receptor 4 signaling, carbamylated NETs (cNETs) instruct monocytes to accelerate osteoclast activation and systemic inflammation.

What is exciting about this article?

Findings from this study suggest that NETs are responsible for the production of a variety of autoantigens in RA and have a direct role in the bone erosion associated with the disease. As such, targeting NET formation during RA might prevent bone damage and mitigate its debilitating effects.

How does this fit into the larger NIAMS portfolio?

Dr. Kaplan’s research focuses on studying abnormalities in neutrophils and understanding the role of NETs in systemic autoimmune disorders. This study discovered a novel role of NETs in elevated osteoclast formation and bone erosion in RA.

Grant support


Research Areas:

Autoimmunity Immunology Molecular Biology and Biochemistry Systems Biology


Neutrophil extracellular trap-associated carbamylation and histones trigger osteoclast formation in rheumatoid arthritis.

O'Neil LJ, Oliveira CB, Wang X, Navarrete M, Barrera-Vargas A, Merayo-Chalico J, Aljahdali R, Aguirre-Aguilar E, Carlucci P, Kaplan MJ, Carmona-Rivera C
Ann Rheum Dis.
2023 May;
doi: 10.1136/ard-2022-223568
PMID: 36737106

Research reported in this publication was supported by the Intramural Research Program of the NIHʼs National Institute of Arthritis and Musculoskeletal and Skin Diseases.