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Objective: In rheumatoid arthritis (RA), anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are commonly used to aid in the diagnosis. Although these autoantibodies are mainly found in RA, their specificity is not optimal. It is therefore difficult to identify RA patients, especially in very early disease, based on the presence of ACPAs and RF alone. In addition, anti-carbamylated protein (anti-CarP) antibodies have diagnostic and prognostic value, since their presence is associated with joint damage in RA patients and also associated with the future development of RA in patients with arthralgia. Therefore, the aim of the present study was to investigate the value of combined antibody testing in relation to prediction and diagnosis of (early) RA., Methods: A literature search resulted in identification of 12 relevant studies, consisting of RA patients, pre-RA individuals, disease controls, healthy first-degree relatives of RA patients, and healthy control subjects, in which data on RF, ACPAs, and anti-CarP antibody status were available. Using these data, random effects meta-analyses were carried out for several antibody combinations., Results: The individual antibodies were highly prevalent in patients with RA (34-80%) compared to the control groups, but were also present in non-RA controls (0-23%). For the classification of most subjects correctly as having RA or as a non-RA control, the combination of ACPAs and/or RF often performed well (specificity 65-100%, sensitivity 59-88%). However, triple positivity for ACPAs, RF, and anti-CarP antibodies resulted in a higher specificity for RA (98-100%), accompanied by a lower sensitivity (11-39%)., Conclusion: As the rheumatology field is moving toward very early identification of RA and possible screening for individuals at maximum risk of RA in populations with a low pretest probability, an autoantibody profile of triple positivity for ACPAs, RF, and anti-CarP provides interesting information that might help identify individuals at risk of developing RA., (© 2018, American College of Rheumatology.)

Objective: To examine whether genetic, environmental, and serologic rheumatoid arthritis (RA) risk factors are associated with inflammatory joint signs in a cohort of first-degree relatives (FDRs) of RA patients., Methods: We evaluated RA risk factors and inflammatory joint signs in a prospective cohort of FDRs without RA in the Studies of the Etiology of RA. Genetic factors included 5 HLA-DRB1 shared epitope alleles and 45 RA-associated single-nucleotide polymorphisms; loci were combined using genetic risk scores weighted by RA risk. Environmental factors (smoking, body mass index, education, and parity) and RA-related autoantibodies were assessed at baseline. Physical examination was performed at baseline and 2-year follow-up, by observers who were blinded with regard to autoantibody status, to assess inflammatory joint signs as tender or swollen joints at sites typical for RA. Logistic regression was performed to evaluate associations of genetic, environmental, and serologic factors with inflammatory joint signs., Results: We analyzed 966 non-Hispanic white FDRs at baseline and 262 at 2-year follow-up after excluding those with inflammatory joint signs at baseline. The mean ± SD age was 47.2 ± 15.5 years, 71% were female, and 55% were shared epitope positive. Smoking >10 pack-years was associated with inflammatory joint signs at baseline (odds ratio [OR] 1.89 [95% confidence interval (95% CI) 1.26-2.82]) and at 2 years (OR 2.66 [95% CI 1.01-7.03]), compared to never smokers. There was a significant interaction between smoking and age with regard to risk of inflammatory joint signs (P = 0.02). FDRs younger than 50 years with >10 pack-years had the highest risk of inflammatory joint signs (OR 4.39 [95% CI 2.22-8.66], compared to never smokers younger than 50 years)., Conclusion: In a high-risk cohort of FDRs, smoking and age were associated with both prevalent and incident inflammatory joint signs at sites typical for RA. Further prospective investigations of the factors affecting the transitions between preclinical RA phases are warranted., (© 2016, American College of Rheumatology.)