RESEARCH - Synovial fluid is a site of citrullination of autoantigens in inflammatory arthritis

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Arthritis Rheum. 2008 Jul 30;58(8):2287-2295.

Synovial fluid is a site of citrullination of autoantigens in

inflammatory arthritis.

Kinloch A, Lundberg K, Wait R, Wegner N, Lim NH, Zendman AJ, Saxne T,

Malmstr V, Venables PJ.

Imperial College London, London, UK.

OBJECTIVE: To examine synovial fluid as a site for generating

citrullinated antigens, including the candidate autoantigen

citrullinated alpha-enolase, in rheumatoid arthritis (RA). METHODS:

Synovial fluid was obtained from 20 patients with RA, 20 patients with

spondylarthritides (SpA), and 20 patients with osteoarthritis (OA).

Samples were resolved using sodium dodecyl sulfate-polyacrylamide gel

electrophoresis, followed by staining with Coomassie blue and

immunoblotting for citrullinated proteins, alpha-enolase, and the

deiminating enzymes peptidylarginine deiminase type 2 (PAD-2) and

PAD-4. Proteins from an RA synovial fluid sample were separated by

2-dimensional electrophoresis, and each protein was identified by

immunoblotting and mass spectrometry. Antibodies to citrullinated

alpha-enolase peptide 1 (CEP-1) and cyclic citrullinated peptide 2

were measured by enzyme-linked immunosorbent assay. RESULTS:

Citrullinated polypeptides were detected in the synovial fluid from

patients with RA and patients with SpA, but not in OA samples.

Alpha-enolase was detected in all of the samples, with mean levels of

6.4 ng/mul in RA samples, 4.3 ng/mul in SpA samples, and <0.9 ng/mul

in OA samples. Two-dimensional electrophoresis provided evidence that

the alpha-enolase was citrullinated in RA synovial fluid. The

citrullinating enzyme PAD-4 was detected in samples from all 3 disease

groups. PAD-2 was detected in 18 of the RA samples, in 16 of the SpA

samples, and in none of the OA samples. Antibodies to CEP-1 were found

in 12 of the RA samples (60%), in none of the SpA samples, and in 1 OA

sample.

CONCLUSION: These results highlight the importance of synovial fluid

for the expression of citrullinated autoantigens in inflammatory

arthritis. Whereas the expression of citrullinated proteins is a

product of inflammation, the antibody response remains specific for

RA.

PMID: 18668562

http://www.ncbi.nlm.nih.gov/pubmed/18668562

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