The Role Of IFN-? On Chemotaxis Of Neutrophils In Rheumatoid Arthritis

Objectives:Rheumatoid arthritis(RA)is a chronic autoimmune disease that often affects cartilage and bone and cause joint deformity..The latest study found that neutrophils play an important role in the pathogenesis of RA.By releasing degradative enzymes,pro-inflammatory cytokines,chemokines and other ways,neutrophils into the joint space and cause tissue damage.Therefore,neutrophils may be a key target for the treatment of RA.This study aims to investigate the levels of IFN-?subtypes(interleukin-29(IL-29),interleukin-28A(IL-28A),interleukin-28B(IL-28B))in the peripheral blood of RA patients.In addition,we also determined the expression of interleukin-28 receptor 1(IL-28R1)on neutrophils of RA and observed the chemotaxis of IL-29,IL-28 A,and IL-28 B on neutrophilsMethods:This study included 30 RA patients and 25 healthy volunteers as a healthy control group.None of the RA patients had been treated with glucocorticoid,DMARDs or biologics(such as TNF inhibitors,rituximab,and abatacept)in 3 months prior to enrollment.All RA patients fulfilling 2010 American College of Rheumatology(ACR)and European League Against Rheumatism(RULAR)classification criteria.First,we used enzyme-linked immunosorbent assay(ELISA)to determine the serum levels of IL-29,IL-28 A,IL-28 B in RA patients.Next,we separated the neutrophils from the peripheral blood of RA patients and by using flow cytometry to detect the IL-28R1 expression on neutrophils.Finally,transwell assay was used to observe the role of IL-29,IL-28 A,and IL-28 B in chemotaxis of neutrophils in RA.Results:(1)The levels of IL-29 in the peripheral blood of RA patients were significantly higher than HC(p = 0.019),and the serum IL-28 B levels were significantly lower than that of the HC(p = 0.020),the serum IL-28 A levels were no statistically difference from HC(p>0.05).(2)The serum IL-29 levels were positively correlated with RF and anti-CCP-antibodies.The serum IL-28 A levels were positively correlated with RF.The serum IL-28 B levels were negatively correlated with RF and anti-CCP-antibodies.(3)The IL-28R1 expression on neutrophils of RA was significantly higher than that of HC(p<0.001).(4)IL-29 and IL-28 A had a significant chemotactic effect on RA neutrophils,while IL-28 B didn't have a significant chemotactic effect on RA neutrophils.Conclusion:In this study,it was found for the first time that the expression of IL-28R1 was significantly increased on neutrophils of RA,and IL-29 and IL-28 A had migration capacity of neutrophils,suggesting that IL-29 and IL-28 A might bind to IL-28R1 on neutrophils and inducing neutrophils to participate in the pathogenesis of RA.Our results provide a new idea for further exploring the pathogenic mechanism of RA and new treatment options.