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.
Highlights
The autoantibody profile of seropositive rheumatoid arthritis (RA) is very diverse and consists of various isotypes and antibodies to multiple post-translational modifications
No studies to date have investigated the effect of composition of the baseline autoantibody profile on early response to conventional Disease-modifying anti-rheumatic drug (DMARD) therapy or long-term drug-free remission (DFR). It is unclear whether the breadth of the profile present at baseline or at the moment of drug-tapering is more indicative the ability of a patient to reach and maintain DFR. To fill these niches in knowledge, we investigated whether outcomes such as early treatment response to DMARDs and DFR are associated with the breadth of the autoantibody profile at baseline in seropositive patients with RA and at the moment of drug-tapering
Since we selected patients based on baseline seropositivity of anti-CCP2 IgG, rheumatoid factor (RF) IgM, or anti-CarP IgG, the high rates of positivity for these antibodies at baseline and 8 months are to be expected (Table 1)
Summary
The autoantibody profile of seropositive rheumatoid arthritis (RA) is very diverse and consists of various isotypes and antibodies to multiple post-translational modifications. Anti-CCP2 and RF-positive patients have a worse long-term prognosis and are less likely to achieve drug-free remission (DFR) [1,2,3,4,5] Whether they differ in early treatment response is controversial [5,6,7,8]. The autoantibody profile is very diverse, with antibodies targeting variable numbers of different peptides with the same post-translational modification, and with marked heterogeneity in isotype usage [12,13,14] This diversity in the breadth of the autoantibody profile most likely reflects the break of tolerance to multiple autoantigens and the maturity of the humoral autoimmune response [15,16,17]
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