Anti-Citrullinated Protein Antibodies Induce Macrophage Subset Disequilibrium in RA Patients

• DOI: 10.1007/s10753-015-0188-z
• Publication Date: 2015-06-11T00:21:05Z
• Authors: Wei Zhu; Xiu Li; Shaohong Fang; Xiaoli Zhang; Ying Wang; Tongshuai Zhang; Zhaoying Li; Yanwen Xu; Siying Qu; Chuanliang Liu; Fei Gao; Haile Pan; Guangyou Wang; Hulun Li; Bo Sun
• Keywords: Male; Macrophages; Transfection; Arthritis, Rheumatoid; 03 medical and health sciences; Phenotype; 0302 clinical medicine; Case-Control Studies; Interferon Regulatory Factors; Synovial Fluid; Citrulline; Humans; Female; RNA Interference; Peptides; Cells, Cultured; Autoantibodies

We used samples from rheumatoid arthritis (RA) patients to examine whether Anti-citrullinated protein antibodies (ACPAs) alter macrophage subset distribution and promote RA development. Macrophage subset distributions and interferon regulatory factor 4 (IRF4) and IRF5 expressions were analyzed. ACPAs were purified by affinity column. After RA and osteoarthritis (OA) patients' macrophages were cocultured with ACPAs, macrophage subsets and IRF4 and IRF5 expressions were measured. Small interfering RNAs (siRNAs) were transfected into ACPA-activated cells to suppress IRF4 or IRF5. Fluorescence-activated cell sorting (FACS), Western blot, and immunohistochemistry were performed. Macrophage subset disequilibrium occurred in RA patient synovial fluids. IRF4 and IRF5 were all expressed in the synovial fluid and synovium. ACPAs (40 IU/ml) could induce macrophages to polarize to M1 subsets, and the percentage of increased M1/M2 ratio of RA patients was higher than that of the OA patients. ACPAs also induce IRF4 and IRF5 protein expressions. IRF5 siRNA transfection impaired ACPA activity significantly. We demonstrated that macrophage subset disequilibrium occurred in RA patients. ACPAs induced IRF5 activity and led to M1 macrophage polarization.