Baseline autoantibody profile in rheumatoid arthritis is associated with early treatment response but not long-term outcomes

Abstract

BackgroundThe autoantibody profile of seropositive rheumatoid arthritis (RA) is very diverse and consists of various isotypes and antibodies to multiple post-translational modifications. It is yet unknown whether this varying breadth of the autoantibody profile is associated with treatment outcomes. Therefore, we investigated whether the composition of the autoantibody profile in RA, as a marker of the underlying immunopathology, influences initial and long-term treatment outcomes.MethodsIn serum from 399 seropositive patients with RA in the IMPROVED study, drawn at baseline and at the moment of drug tapering, we measured IgG, IgM, and IgA isotypes for anti-cyclic citrullinated peptide-2 and anti‐carbamylated protein antibodies, IgM and IgA rheumatoid factor, and reactivity against four citrullinated and two acetylated peptides (anti-modified protein antibodies (AMPAs)). We investigated the effect of the breadth of the autoantibody profile on (1) change in disease activity score (DAS)44 between 0 and 4 months, (2) initial drug-free remission (DFR, drug-free DAS44 < 1.6) achieved between 1 and 2 years of follow up, and (3) long-term sustained DFR until last follow up.ResultsPatients with a broad autoantibody profile at baseline had a significantly better early treatment response: ΔDAS 0–4 months of 1–2, 3–4, and 5–6 vs 7–8 isotypes, -1.5 (p < 0.001), -1.7 (p = 0.03), and -1.8 (p = 0.04) vs -2.2. Similar results were observed for AMPA number. However, patients with a broad baseline autoantibody profile achieved less initial DFR. For long-term sustained DFR there was no longer an association with the breadth of the autoantibody response. When assessing autoantibodies at the moment of tapering, similar trends were observed.ConclusionsA broad baseline autoantibody profile is associated with a better early treatment response. The breadth of the baseline autoantibody profile, reflecting a break in tolerance against several different autoantigens and extensive isotype switching, may indicate a more active humoral autoimmunity, which could make the underlying disease processes initially more suppressible by medication. The lack of association with long-term sustained DFR suggests that the relevance of the baseline autoantibody profile diminishes over time.Trial registrationISRCTN11916566. Registered on 7 November 2006. EudraCT, 2006- 06186-16. Registered on 16 July 2007.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1520-4) contains supplementary material, which is available to authorized users.

Improved classification of rheumatoid arthritis with a score including anti-acetylated ornithine antibodies

“…The other explored approach, aimed to use the anti-AcOrn as a biomarker for the RF and anti-CCP "seronegative" patients, did not result in meaningful improvements. Other reports have already signalled the anti-AcOrn antibodies outperform several other AAPA as RA biomarkers although they did not explore RA classification [18][19][20][21][22] . The combination of anti-AcOrn with anti-AcLys did not result in significant improvements in sensitivity, probably because of the high concordance between them.…”

Autoantibodies and B Cells: The ABC of rheumatoid arthritis pathophysiology

“…Once disease has developed, the value of anti‐CarP regains its importance: The presence of anti‐CarP has been independently associated with higher disease activity at baseline and over time, as well as with radiographic damage . At baseline, a broad autoantibody profile regarding different isotypes of RF, ACPA, and anti‐CarP is associated with early treatment response; but the importance of this broad profile diminishes over time . Intensity of treatment correlates with a decrease in autoantibody levels and reflects the level of immunosuppression, although this detectable decrease has only limited relevance for clinical activity and long‐term treatment response .…”

“…88,89 At baseline, a broad autoantibody profile regarding different isotypes of RF, ACPA, and anti-CarP is associated with early treatment response; but the importance of this broad profile diminishes over time. 90 Intensity of treatment correlates with a decrease in autoantibody levels and reflects the level of immunosuppression, although this detectable decrease has only limited relevance for clinical activity and long-term treatment response. 91 These observations shed light on the possible role of autoantibodies in (pre-)RA patients, although their exact functions need to be elucidated in future studies.…”

In RA, becoming seronegative over the first year of treatment does not translate to better chances of drug-free remission

“…In baseline and 1-year serum of 381 patients with seropositive RA, we measured 14 RA-associated autoantibodies by ELISA2: anti-CCP2 IgG, IgM and IgA; rheumatoid factor IgM and IgA; anti-CarP IgG, IgM and IgA; anti-acetylated   lysine vimentin IgG and anti-acetylated ornithine vimentin IgG (Orgentec Diagnostika , Germany); and anti-citrullinated vimentin 59–74 IgG, anti-citrullinated fibrinogen β 36–52 and α 27–43 IgG, anti-citrullinated enolase 5–20 IgG. Patients originated from the IMPROVED study,3 a randomised controlled treat-to-target trial of early (<2 years) untreated RA, steered at disease activity score remission (DAS44<1.6) and DFR, with initial treatment of methotrexate and high-dose prednisone.…”