Increased expression of activation-induced cytidine deaminase is associated with anti-CCP and rheumatoid factor in rheumatoid arthritis.
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.
Xu
X
X
Department of Physiology and Physics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Hsu
H-C
HC
Chen
J
J
Grizzle
W E
WE
Chatham
W W
WW
Stockard
C R
CR
Wu
Q
Q
Yang
P A
PA
Holers
V M
VM
Mountz
J D
JD
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D003564:Cytidine Deaminase / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D005260:Female; D018858:Germinal Center / Q000201:enzymology / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D012217:Rheumatoid Factor / Q000097:blood / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D001323:Autoantibodies; D020381:Interleukin-17; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D007371:Interferon-gamma; D012217:Rheumatoid Factor; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
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