A protective ACPA

Autoantibodies known as anti-citrullinated protein antibodies (ACPAs) are established markers for the classification and progression of rheumatoid arthritis (RA); they are often associated with severe disease but can be detectable long before the clinical onset of RA. Given these associations, ACPAs are expected to be involved in RA pathogenesis, but data in support of this conclusion are limited, and an article now published in Nature Communications lends weight to some earlier studies suggesting that some ACPAs are actually protective. The researchers made a panel of RA-patient-derived monoclonal ACPAs, including some that were humanized. Passive transfer of these antibodies into mice was not arthritogenic, and one of the antibodies (clone E4) protected mice against collagen-antibody-induced arthritis. Mechanistic experiments indicated that protection by E4 required an interaction with citrullinated α-enolase in the synovial fluid that resulted in the formation of immune complexes that were able stimulate macrophages via Fc receptors. This interaction resulted in reduced osteoclastogenesis (an important driver of characteristic bone erosion and joint pathology in RA) and increased production of the cytokine IL-10 that would limit damaging inflammation.

留言 (0)

沒有登入
gif