The acute phase reactant orosomucoid-2 directly promotes rheumatoid inflammation

Acute phase proteins involved in chronic inflammatory diseases have not been systematically analyzed. Here, global proteome profiling of serum and urine revealed that orosomucoid-2 (ORM2), an acute phase reactant, was differentially expressed in rheumatoid arthritis (RA) patients and showed the highest fold change. Therefore, we questioned the extent to which ORM2, which is produced mainly in the liver, actively participates in rheumatoid inflammation. Surprisingly, ORM2 expression was upregulated in the synovial fluids and synovial membranes of RA patients. The major cell types producing ORM2 were synovial macrophages and fibroblast-like synoviocytes (FLSs) from RA patients. Recombinant ORM2 robustly increased IL-6, TNF-alpha, CXCL8 (IL-8), and CCL2 production by RA macrophages and FLSs via the NF-kappa B and p38 MAPK pathways. Interestingly, glycophorin C, a membrane protein for determining erythrocyte shape, was the receptor for ORM2. Intra-articular injection of ORM2 increased the severity of arthritis in mice and accelerated the infiltration of macrophages into the affected joints. Moreover, circulating ORM2 levels correlated with RA activity and radiographic progression. In conclusion, the acute phase protein ORM2 can directly increase the production of proinflammatory mediators and promote chronic arthritis in mice, suggesting that ORM2 could be a new therapeutic target for RA. This research aimed to explore the function of Orosomucoid-2, a protein produced during the body's initial response to injury, in rheumatoid arthritis, a chronic inflammatory disorder. It was found that ORM2 was produced in large quantities by synovial fibroblasts in RA patients. When these cells were treated with ORM2, they produced inflammation-causing substances, indicating ORM2 could contribute to RA inflammation. The study also identified Glycophorin C as a receptor for ORM2 on these cells. In mice, ORM2 was found to worsen arthritis and increase the presence of macrophages. In RA patients, the levels of ORM2 in the blood correlated with disease activity and progression. These findings suggest that ORM2 could be a potential diagnostic marker and treatment target for RA. More research is needed to further understand ORM2's role in other chronic inflammatory diseases.This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.