RESEARCH - Antibodies to several citrullinated antigens are enriched in the joints of RA patients

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Arthritis Rheum. 2009 Dec 28;62(1):44-52.

Antibodies to several citrullinated antigens are enriched in the

joints of rheumatoid arthritis patients.

Snir O, Widhe M, Hermansson M, von Spee C, Lindberg J, Hensen S,

Lundberg K, Engström A, Venables PJ, Toes RE, Holmdahl R, Klareskog L,

Malmström V.

Karolinska University Hospital, and Karolinska Institutet at Solna,

Stockholm, Sweden.

OBJECTIVE: High titers of specific anti-citrullinated protein

antibodies (ACPAs) are frequently present in the serum of rheumatoid

arthritis (RA) patients, but their presence in synovial fluid is less

well characterized. The purpose of this study was to compare the

levels of antibody to 4 well-defined citrullinated candidate RA

autoantigens in serum and synovial fluid and to determine whether

antibodies to one citrullinated antigen are dominant over another.

Furthermore, we studied their relationships with mutated citrullinated

vimentin (MCV), a newly identified RA-specific serum assay, and the

classic cyclic citrullinated peptide (CCP) in the synovial fluid of

well-defined HLA-DR groups.

METHODS: Paired serum and synovial fluid samples from 290 RA patients

and serum samples from 100 age- and sex-matched healthy controls were

analyzed for the presence of anti-MCV and anti-CCP antibodies and for

reactivity to citrullinated fibrinogen, alpha-enolase, type II

collagen, and vimentin. A total of 219 of the 290 patients were

genotyped for the HLA-DR shared epitope alleles.

RESULTS: Significantly higher proportions of antibodies against all

RA-associated citrullinated antigens were found in synovial fluid as

compared with serum. This was also true for the MCV and CCP responses

but not for non-RA-associated anti-tetanus toxoid antibodies. As

expected, we found a high correlation between citrullinated vimentin

and MCV responses. All synovial fluid ACPAs were predominantly

associated with HLA-DRB1*04 alleles and were confined to the CCP+/MCV+

subset of patients.

CONCLUSION: MCV and CCP positivity represent a similar subset of RA

patients, whereas ACPAs with different fine specificities fall into

subgroups of anti-CCP+/anti-MCV+ patients. The levels of all specific

ACPAs were elevated in synovial fluid, suggesting that there is local

antibody production and/or retention of ACPAs at the site of

inflammation governed by RA-predisposing genes.

PMID: 20039432

http://www.ncbi.nlm.nih.gov/pubmed/20039432

Not an MD