Biobanking and nested case–control studies demonstrating that autoantibodies and other biomarkers precede the diagnosis of seropositive clinical RA
| Aho et al (199182 and 200083) | Finnish health-survey/biobank studies that identified RF and antibodies to filaggrin precede onset of clinical RA. |
| Rantapää-Dahlqvist et al12 and Kokkonen et al16 | Swedish biobank study demonstrating that RF isotypes and ACPA (by anti-CCP2 assay) as well as numerous cytokines and chemokines were elevated prior to RA diagnosis. |
| Nielen et al13 | Dutch biobank study demonstrating that RF and ACPA (by anti-CCP first generation assay) were elevated prior to RA diagnosis. |
| Majka et al14 and Deane et al15 | USA Department of Defense biobank study demonstrating that RF and ACPA (by anti-CCP2 assay) were elevated prior to RA diagnosis and levels of cytokines/chemokines increase as diagnosis approaches. |
| Arkema et al84 | USA Nurses’ Health Study cohort reporting ACPA reactivity up to 10 years before RA onset. Those with high ACPA levels carrying the HLA-DRB1 shared epitope were at highest risk. |
ACPA, anticitrullinated protein antibody; anti-CCP, anti-cyclic citrullinated peptide antibody; RA, rheumatoid arthritis; RF, rheumatoid factor.