Increased expression of activation-induced cytidine deaminase is associated with anti-CCP and rheumatoid factor in rheumatoid arthritis

Scand J Immunol. 2009 Sep;70(3):309-16. doi: 10.1111/j.1365-3083.2009.02302.x.

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-gamma (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-gamma and IL-17, leading to the development of anti-CCP and RF.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • B-Lymphocytes / enzymology*
  • B-Lymphocytes / immunology
  • Cytidine Deaminase / biosynthesis*
  • Cytidine Deaminase / genetics
  • Cytidine Deaminase / immunology
  • Female
  • Germinal Center / enzymology
  • Germinal Center / immunology
  • Humans
  • Interferon-gamma / blood
  • Interleukin-17 / blood
  • Male
  • Middle Aged
  • Peptides, Cyclic / immunology*
  • Rheumatoid Factor / blood
  • Rheumatoid Factor / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology

Substances

  • Autoantibodies
  • Interleukin-17
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • Interferon-gamma
  • Rheumatoid Factor
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase