Diagnostic and prognostic value of antibodies against chimeric fibrin/filaggrin citrullinated synthetic peptides in rheumatoid arthritis.
BACKGROUND
Evidence suggests that citrullinated fibrin(ogen) may be a potential in vivo target of anticitrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis (RA). We compared the diagnostic yield of three enzyme-linked immunosorbent assay (ELISA) tests by using chimeric fibrin/filaggrin citrullinated synthetic peptides (CFFCP1, CFFCP2, CFFCP3) with a commercial CCP2-based test in RA and analyzed their prognostic values in early RA.


METHODS
Samples from 307 blood donors and patients with RA (322), psoriatic arthritis (133), systemic lupus erythematosus (119), and hepatitis C infection (84) were assayed by using CFFCP- and CCP2-based tests. Autoantibodies also were analyzed at baseline and during a 2-year follow-up in 98 early RA patients to determine their prognostic value.


RESULTS
With cutoffs giving 98% specificity for RA versus blood donors, the sensitivity was 72.1% for CFFCP1, 78.0% for CFFCP2, 71.4% for CFFCP3, and 73.9% for CCP2, with positive predictive values greater than 97% in all cases. CFFCP sensitivity in RA increased to 80.4% without losing specificity when positivity was considered as any positive anti-CFFCP status. Specificity of the three CFFCP tests versus other rheumatic populations was high (> 90%) and similar to those for the CCP2. In early RA, CFFCP1 best identified patients with a poor radiographic outcome. Radiographic progression was faster in the small subgroup of CCP2-negative and CFFCP1-positive patients than in those negative for both autoantibodies. CFFCP antibodies decreased after 1 year, but without any correlation with changes in disease activity.


CONCLUSIONS
CFFCP-based assays are highly sensitive and specific for RA. Early RA patients with anti-CFFCP1 antibodies, including CCP2-negative patients, show greater radiographic progression.
Sanmartí
Raimon
R
Rheumatology Service, Hospital Clínic of Barcelona, IDIBAPS, Villarroel 170, 08036 Barcelona, Spain. sanmarti@clinic.ub.es
Graell
Eduard
E
Perez
Maria L
ML
Ercilla
Guadalupe
G
Viñas
Odette
O
Gómez-Puerta
Jose A
JA
Gratacós
Jordi
J
Balsa
Alejandro
A
Gómara
Maria J
MJ
Larrosa
Marta
M
Cañete
Juan D
JD
Haro
Isabel
I
D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D002956:Citrulline / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005337:Fibrin / Q000276:immunology* / Q000378:metabolism; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011993:Recombinant Fusion Proteins; D012680:Sensitivity and Specificity
D001323:Autoantibodies; D001324:Autoantigens; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D011993:Recombinant Fusion Proteins; D002956:Citrulline; D005337:Fibrin