Document Detail


Increased expression of activation-induced cytidine deaminase is associated with anti-CCP and rheumatoid factor in rheumatoid arthritis.
MedLine Citation:
PMID:  19703021     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
X Xu; H-C Hsu; J Chen; W E Grizzle; W W Chatham; C R Stockard; Q Wu; P A Yang; V M Holers; J D Mountz
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Scandinavian journal of immunology     Volume:  70     ISSN:  1365-3083     ISO Abbreviation:  Scand. J. Immunol.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-25     Completed Date:  2009-09-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0323767     Medline TA:  Scand J Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  309-16     Citation Subset:  IM    
Affiliation:
Department of Physiology and Physics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
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MeSH Terms
Descriptor/Qualifier:
Aged
Arthritis, Rheumatoid / blood,  immunology*,  pathology
Autoantibodies / blood,  immunology*
B-Lymphocytes / enzymology*,  immunology
Cytidine Deaminase / biosynthesis*,  genetics,  immunology
Female
Germinal Center / enzymology,  immunology
Humans
Interferon-gamma / blood
Interleukin-17 / blood
Male
Middle Aged
Peptides, Cyclic / immunology*
Rheumatoid Factor / blood,  immunology*
T-Lymphocytes, Helper-Inducer / immunology
Grant Support
ID/Acronym/Agency:
R01 1AI 071110-01A1/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/Interleukin-17; 0/Peptides, Cyclic; 0/cyclic citrullinated peptide; 82115-62-6/Interferon-gamma; 9009-79-4/Rheumatoid Factor; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase

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