Table 2

Articles reporting on RA-related autoantibodies as isolated risk factors in individuals at risk of RA

StudyPopulation studiedCohort sizeRisk factorFrequency assessedMain outcome
del Puente et al9Healthy NAN2712RFMultiple:
RA development
Incidence of RA (cases per 1000 person-years) increased according to RF titre (p<0.001):
cases per 1000 person-years=2.4 (RF titre <1:2); 6.7 (titre 1:2–1:16); 11.0 (titre 1:32–1:256); 48.3 (titre >1:256)
Ramos-Remus et al6FDRs and relatives of RA probands819 relatives of 252 RA probandsRelatives of RA probandsOnce (BL)Development of RA
All relatives
Anti-CCP2+/RF+ versus seronegative: HR 52.5 (95% CI 19.1 to 144.1), p<0.01
Offspring versus other relatives
HR 3.1 (95% CI 1.2 to 8.1)
Gan et al52Anti-CCP3-positive individuals screened from the general population35Anti-CCP3Once (BL)Development of IA
Anti-CCP3: 14/35 (40%) of anti-CCP3+ individuals developed IA at 2.56 years follow-up
Verheul et al60Pre-RA individuals, FDRs379 (pre-RA)
246 (FDR)
Meta-analysisDevelopment of RA
Number of different autoantibodies present:
one antibody: OR 12 (95% CI 6 to 21)
two antibodies: OR 30 (95% CI 11 to 83)
three antibodies: OR 112 (95% CI 6 to 2122)
Tanner et al7Unaffected relatives of NAN RA-probands in Canada and Alaska374ACPA
BL and annually
Development of IA
Cases of IA per 1000 person-years:
ACPA+/RF+ 97.1
ACPA−/RF+ 7.2
ACPA+/RF− 36.4
Hafkenscheid et al8ACPA-positive FDRs of patients with RA, in NANs126IgG ACPA V‐domain glycosylationDevelopment of RA
IgG ACPA variable‐domain glycosylation:
HR=6.07 (95% CI 1.46 to 25.2, p=0.013)
MSK symptoms without arthritis
Bos et al11Seropositive arthralgia (ACPA and/or RF)147
(50 ACPA+, 52 RF+, 45 ACPA+/RF+)
Once (BL)Development of IA
Compared with RF:
anti-CCP: HR 6.0 (95% CI 1.8 to 19.8); p=0.004
In anti-CCP+ only:
anti-CCP+/IgM RF+: HR 3.0 (95% CI 1.4 to 6.9), p=0.01.
High anti-CCP level: HR 1.7; (95% CI 1.1 to 2.5), p=0.008
van de Stadt et al12Seropositive arthralgia (ACPA and/or RF)244Reactivity to five citrullinated peptides: cFib1
enolase vimentin
Once (BL)Development of IA
Recognition of 2–5 additional citrullinated peptides: HR 1.7 (95% CI 0.93 to 3.16), p=0.08
Shi et al16Seropositive arthralgia (anti-CCP2 and/or RF)340Anti-CarP AbOnce (BL)Development of IA
Anti-CarP antibodies: HR=1.56 (95% CI 1.06 to 2.29), p=0.003.
In anti-CCP+ subgroup only:
anti-CarP antibodies: HR=2.23 (95% CI 1.31 to 3.79), p=0.003
Ten Brinck et al13CSA241ACPA, RF and anti-CarP AbOnce (BL)Development of IA
Anti-CCP2: HR=5.1 (95% CI 2.0 to 13.2)
RF: 2.0 (95% CI 0.81 to 4.9)
Anti-CarP: 1.04 (95% CI 0.46 to 2.4)
Early clinical arthritis
Kudo-Tanaka et al17Recent-onset (<2 years) UA (arthritis in ≥2 joints not meeting RA or other classification criteria)146Anti-CCP
Once (BL)RA development
(PPV, NPV and diagnostic accuracy) anti-CCP2: 65.2%, 97.2%, 91.7%, respectively;
IgM RF: 34.1%, 95.6%, 76.3%, respectively;
CARF: 30.2%, 97.5%, 70.5%, respectively;
MMP3: 25.0%, 91.5%, 69.0%, respectively
van der Linden et al19Early (<2 years) UA625Anti-CCP2
Once (BL)RA development
Anti-CCP2: 67.1%
Anti-CCP3: 64%
Anti-MCV: 56.3%
Mjaavatten et al18UA (≥1 clinically swollen joint of ≤16 weeks duration)376Anti-CCP2
Anti-CCP2+/IgM RF+
Once (BL)Development of persistent IA
Anti-CCP: OR 3.567 (95% CI 1.572 to 8.094)
IgM RF: OR 2.716 (95% CI 1.189 to 6.202)
Anti-CCP+/RF+: OR 7.948 (95% CI 2.659 to 23.752)
  • HR/OR and 95% CIs have been reported where available.

  • +, positive; Ab, antibodies; ACPA, anticyclic citrullinated peptide antibodies; BL, baseline; CARF, anti-agalactosyl IgG antibodies; CarP, carbamilated protein; CCP, cyclic citrullinated peptide; CCP2, second-generation anti-CCP Ab; CCP3, third-generation anti-CCP Ab; CSA, clinically suspect arthralgia; FDRs, first-degree relatives; IA, inflammatory arthritis; MCV, mutated citrullinated vimentin; MMP-3, matrix metalloproteinase 3; NAN, native American nations; NPV, negative predictive value; PPV, positive predictive value; RA, rheumatoid arthritis; RF, rheumatoid factor; UA, undifferentiated arthritis.