Increased Expression of Activation‐Induced Cytidine Deaminase is Associated with Anti‐CCP and Rheumatoid Factor in Rheumatoid Arthritis

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Abstract
Rheumatoid arthritis (RA) is associated with higher levels of autoantibodies and IL‐17. Here, we investigated if ectopic lymphoid follicles and peripheral blood mononuclear cells (PBMCs) from RA patients exhibit increased activation‐induced cytidine deaminase (AID), and if increased AID is correlated with serum levels of autoantibodies and IL‐17. The results of immunohistochemical staining showed that organized AID+ germinal centres were observed in six of the 12 RA synovial samples, and AID+ cells were found almost exclusively in the B‐cell areas of these follicles. Aggregated but not organized lymphoid follicles were found in only one OA synovial sample without AID+ cells. Significantly higher levels of AID mRNA (Aicda) detected by RT‐PCR were found in the PBMCs from RA patients than PBMCs from normal controls (P < 0.01). In the PBMCs from RA patients, AID was expressed predominately by the CD10+IgM+CD20+ B‐cell population and the percentage of these cells that expressed AID was significantly higher than in normal controls (P < 0.01). AID expression in the PBMCs correlated significantly and positively with the serum levels of rheumatoid factor (RF) (P ≤ 0.0001) and anti‐cyclic citrullinated peptide (CCP) (P = 0.0005). Serum levels of IFN‐γ (P = 0.0005) and IL‐17 (P = 0.007), but not IL‐4, also exhibited positive correlation with the expression of AID. These results suggest that the higher levels of AID expression in B cells of RA patients correlate with, and may be associated with the higher levels of T helper cell cytokines IFN‐γ and IL‐17, leading to the development of anti‐CCP and RF.