RESEARCH - Synovial intracellular citrullinated proteins in RA

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Arthritis Rheum. 2005 Aug;52(8):2323-30.

Synovial intracellular citrullinated proteins colocalizing with peptidyl

arginine deiminase as pathophysiologically relevant antigenic determinants

of rheumatoid arthritis-specific humoral autoimmunity.

De Rycke L, AP, Cantaert T, Kruithof E, Echols JD, Vandekerckhove

B, Veys EM, De Keyser F, Baeten D.

Ghent University Hospital, Ghent, Belgium.

OBJECTIVE: To address the ongoing debate concerning the specificity of

synovial citrullinated proteins for rheumatoid arthritis (RA) and to analyze

their pathophysiologic relevance to the induction or perpetuation of the

RA-specific anti-citrullinated protein antibodies (ACPAs). METHODS: Synovium

of 19 RA patients and 19 non-RA controls was immunostained for the presence

of citrullinated proteins with a mouse monoclonal antibody (F95), for the

citrullinating enzyme peptidyl arginine deiminase type 2 (PAD-2), and for

the free citrulline-producing enzyme inducible nitric oxide synthase (iNOS).

Extending the RA cohort to 61 patients, the findings of anticitrulline

staining in synovium were related to serum and synovial fluid ACPA levels,

as measured by enzyme-linked immunosorbent assay. RESULTS: F95 staining

indicated the presence of synovial intracellular citrullinated proteins in

53% of RA samples versus 5% of control samples, whereas extracellular

staining was not RA specific. Immunoblotting and inhibition experiments

confirmed that the antibody recognized citrullinated proteins but not free

citrulline. Accordingly, iNOS was equally found in RA and control synovium

and in intracellular citrullinated protein-positive and intracellular

citrullinated protein-negative samples. In contrast, intracellular

citrullinated proteins colocalized with PAD-2, which was found in 59% of RA

samples versus 17% of control samples. Independent of local disease

activity, the presence of the RA-specific synovial intracellular

citrullinated proteins was associated with significantly higher systemic and

local ACPA levels and with local ACPA production in the joint.

CONCLUSION: These data confirm the presence of RA-specific intracellular

citrullinated proteins in synovium. The link with PAD-2 and local and

systemic ACPA levels emphasizes their pathophysiologic relevance for

RA-specific humoral autoimmunity.

PMID: 16052592

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

6052592 & dopt=Abstract

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