Autoantibodies as prognostic markers in rheumatoid arthritis

Abstract

Background and purpose: Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by progressively destructive polyarthritis. Key autoimmune features include the presence of autoantibodies. The purpose of this review is to discuss the diagnostic and prognostic properties of rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA), based on current use in Sweden. Furthermore, we discuss their relation to disease outcomes and their importance for management of patients with RA.

Principal findings: Based on current cut-offs, ACPA has a higher specificity for RA than RF, and testing for ACPA alone is recommended when investigating patients with clinically suspect RA. The diagnostic utility of RF may improve with adjusted reference range/upper limit of normal.RF and ACPA both predict rapid radiographic progression, severe extra-articular manifestations and mortality, whereas other outcomes, such as osteoporosis, pain and disability are not as clearly related to seropositivity. RF/ACPA positive patients respond better to some targeted therapies, in particular rituximab, compared to seronegative RA patients. Recent studies indicate that treatment of ACPA-positive arthralgia with abatacept may delay and perhaps sometimes even prevent development of arthritis. Available evidence does not support an added value of repeated RF or ACPA testing.

Conclusions: Testing for ACPA in patients with arthralgia or suspected early RA, and for ACPA and RF at RA diagnosis, provides useful diagnostic and prognostic information, which has implications for follow-up and treatment. Repeated testing for ACPA and RF is not recommended. Potential future developments include treatment of ACPA-positive individuals for prevention of arthritis.

Keywords: Anti-citrullinated peptide antibodies; Extra-articular manifestations; Prognosis; Rapid radiographic progression; Rheumatoid arthritis; Rheumatoid factor.

Fig. 1

Autoantibodies and other baseline factors, by subsequent occurrence of severe extra-articular manifestations of RA. Data from a case-control study of patients with severe extra-articular RA (vasculitis, pericarditis, pleuritis, Felty's syndrome, scleritis, episcleritis, glomerulonephritis) and RA controls without such extra-articular manifestations, matched for duration of RA and centre. The sample was pooled from studies performed at the Mayo Clinic, Rochester, Minnesota, in Malmö and Lund, Sweden, and from the Swedish multicentre study BARFOT. ∗∗p < 0.001; ∗p = 0.001.

Fig. 2

Baseline autoantibodies and history of ever smoking, by subsequent development of interstitial lung disease (ILD). Data from a large multi-centre study of patients with early RA in the United Kingdom, with structured long-term follow-up of the occurrence of ILD. ∗∗∗p = 0.006; ∗∗p = 0.01; ∗p = 0.02.

Fig. 3

Prevalences of osteopenia and osteoporosis at follow-up visits in early RA, ACPA status. Osteopenia was defined as BMD T-score ≤ -1, but > -2,5. Osteporosis was defined as BMD T-score ≤ -2.5. Data from RA diagnosis and after 5 years and 10 years of follow-up in the Malmö early RA cohort. ∗p = 0.04.

Fig. 4

Proportions with positive ACPA at RA diagnosis by presence of unacceptable pain with low inflammation at follow-up. Unacceptable pain with low inflammation was defined as VAS pain>40 and CRP<10 mg/l at each follow-up visit up to 5 years. ACPA positive patients were less likely to experience unacceptable pain with low inflammation at 5 years (odds ratio 0.50; 95 % confidence interval 0.22–0.98).