Antibodies to mutated citrullinated vimentin for diagnosing rheumatoid arthritis in anti-CCP-negative patients and for monitoring infliximab therapy.
BACKGROUND
Antibodies against cyclic citrullinated peptides (CCPs) are useful for diagnosing rheumatoid arthritis (RA). Antibodies to mutated citrullinated vimentin (MCV) were described recently in RA. The aims of this study were to evaluate the usefulness of anti-MCV for diagnosing RA in anti-CCP-negative patients and to monitor anti-MCV titres during infliximab therapy for RA.


METHODS
We studied two groups of RA patients, one with (n = 80) and one without (n = 76) anti-CCP antibodies. The specificity of anti-MCV was evaluated by investigating 50 healthy controls and 158 patients with other rheumatic diseases (51 psoriatic rheumatism, 58 primary Sjögren syndrome, and 49 ankylosis spondylitis). Serum anti-MCV and anti-CCP titres were measured in 23 patients after 6, 12, 18, and 24 months of infliximab treatment. Anti-CCP2 and anti-MCV levels were assayed using a commercial enzyme-linked immunosorbent assay. IgM rheumatoid factor was determined by nephelometry.


RESULTS
In accordance with the cutoff values recommended by the manufacturer, the specificity of anti-MCV antibodies was 90.9%. We adjusted the cutoff values to obtain the same specificity as that of anti-CCP antibodies (94.2%). With this optimal cutoff, anti-MCV antibodies were found in 11.8% (9/76) of RA patients without anti-CCP, and similarly, anti-CCP antibodies were found in 11.2% (9/80) of RA patients without anti-MCV. Anti-MCV antibodies were positive in 6 patients who tested negative for both anti-CCP and rheumatoid factor. Anti-MCV titres were significantly decreased after 18 and 24 months of infliximab therapy compared with baseline (P < 0.01) as a significant decrease of anti-CCP levels occurred only at 24 months (P < 0.04). Moreover, an anti-MCV decrease was significantly associated with DAS28 (disease activity score using 28 joint counts) improvements 12 months into therapy.


CONCLUSIONS
Our results suggest that anti-MCV antibodies may be valuable for diagnosing RA in anti-CCP-negative patients without replacing them as an equivalent number of anti-CCP-positive RA patients test negative for anti-MCV. Moreover, anti-MCV antibodies could be useful for monitoring the effects of infliximab therapy.
Nicaise Roland
Pascale
P
Immunology and Haematology Department, Bichat-Claude Bernard Teaching Hospital, AP-HP, Paris Cedex 18, France. pascale.nicaise@bch.aphp.fr
Grootenboer Mignot
Sabine
S
Bruns
Alessandra
A
Hurtado
Margarita
M
Palazzo
Elisabeth
E
Hayem
Gilles
G
Dieudé
Philippe
P
Meyer
Olivier
O
Chollet Martin
Sylvie
S
D000911:Antibodies, Monoclonal / Q000097:blood* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D001323:Autoantibodies / Q000097:blood*; D002956:Citrulline / Q000097:blood; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D000069285:Infliximab; D009154:Mutation; D010456:Peptides, Cyclic / Q000097:blood*; D014746:Vimentin / Q000097:blood*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D010456:Peptides, Cyclic; D014746:Vimentin; C487763:cyclic citrullinated peptide; D002956:Citrulline; D000069285:Infliximab