Antibodies against mutated citrullinated vimentin are a better predictor of disease activity at 24 months in early rheumatoid arthritis than antibodies against cyclic citrullinated peptides.
OBJECTIVE
To evaluate the predictive values for disease progression of various antibodies against citrullinated peptide proteins (ACPA) and their relation to PTPN22 1858C/T polymorphism and HLA-DRB1 alleles in early rheumatoid arthritis (RA).


METHODS
The ACPA, e.g., antibodies against mutated citrullinated vimentin (MCV), cyclic citrullinated peptides (CCP) type 2 and 3 (both of IgG isotype) and 3.1 (of both IgG and IgA isotypes), were analyzed at baseline in patients with early RA (n = 210) and in population controls (n = 102) using an enzyme immunoassay. A receiver-operating characteristic curve was constructed for each antibody. Disease activity [swollen and tender joints, visual analog scale for global health, and erythrocyte sedimentation rate (ESR)] was evaluated at baseline and regularly for 24 months. Radiographs of hands and feet were graded using the Larsen score.


RESULTS
Patients with anti-MCV antibodies had significantly less reduction in Disease Activity Score (DAS28) over time (p < 0.01), and significantly increased area under the curve (AUC) for DAS28 (p < 0.05), ESR (p < 0.01), C-reactive protein (p < 0.01), and swollen joint count (p = 0.057) compared to those without. Corresponding differences were not found in patients with anti-CCP2, CCP3, and CCP3.1 antibodies. Radiological progression (p < 0.0001-0.01) and radiological outcome (p < 0.0001-0.01) at 24 months were significantly predicted by all ACPA after baseline adjustments. PTPN22 T variant and HLA-DRB1 alleles were not related to radiological progression or inflammatory activity over time.


CONCLUSIONS
Anti-MCV antibodies are associated with a more severe RA disease, as measured by DAS28, ESR, and swollen joint count over time, compared with anti-CCP2, CCP3, and CCP3.1 antibodies. Radiological progression was predicted equally by all 4 autoantibodies.
Innala
Lena
L
Department of Rheumatology, Department of Clinical Immunology, and Department of Transfusion Medicine, University Hospital, Umeå, Sweden.
Kokkonen
Heidi
H
Eriksson
Catharina
C
Jidell
Erik
E
Berglin
Ewa
E
Dahlqvst
Solbritt Rantapää
SR
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood*; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012217:Rheumatoid Factor / Q000097:blood; D012720:Severity of Illness Index; D054063:Superior Sagittal Sinus; D014746:Vimentin / Q000276:immunology*
D001323:Autoantibodies; D015415:Biomarkers; D010456:Peptides, Cyclic; D014746:Vimentin; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor