The role of anti-citrullinated protein antibody reactivities in an inception cohort of patients with rheumatoid arthritis receiving treat-to-target therapy

Abstract

BackgroundAnti-citrullinated protein antibody (ACPA) reactivities precede clinical onset of rheumatoid arthritis (RA), and it has been suggested that ACPA reactivities towards distinct target proteins may be associated with differences in RA phenotypes. We aimed to assess the prevalence of baseline ACPA reactivities in an inception cohort of patients with early RA, and to investigate their associations with disease activity, treatment response, ultrasound findings and radiographic damage.MethodsDisease-modifying antirheumatic drug (DMARD)-naïve patients with early RA, classified according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria, were included in the ARCTIC trial and assessed in the present analysis. During follow up, patients were monitored frequently and treatment was adjusted according to a predetermined protocol, starting with methotrexate monotherapy with prednisolone bridging. Analysis of 16 different ACPA reactivities targeting citrullinated peptides from fibrinogen, alpha-1 enolase, vimentin, filaggrin and histone was performed using a multiplex chip-based assay. Samples from 0, 3, 12 and 24 months were analysed. Controls were blood donors with similar characteristics to the patients (age, gender, smoking status).ResultsA total of 217 patients and 94 controls were included. Median [25, 75 percentile] number of ACPA reactivities in all patients was 9 [4, 12], and were most prevalent in anti-cyclic citrullinated peptide /rheumatoid factor-positive patients 10 [7, 12]. Disease activity measures and ultrasound scores at baseline were lower in ACPA reactivity-positive compared to ACPA reactivity-negative patients. ACPA reactivity levels decreased after 3 months of DMARD treatment, most pronounced for fibrinogenβ 60–74 to 62% of baseline antibody level, with least change in filaggrin 307–324 to 81% of baseline antibody level, both p < 0.001. However, outcomes in disease activity measures, ultrasound and radiographic scores after 12 and 24 months were not associated with baseline levels or changes in ACPA reactivity levels and/or seroreversion after 3 months.ConclusionsThe clinical relevance of analysing ACPA reactivities in intensively treated and closely monitored early RA was limited, with no apparent associations with disease activity, prediction of treatment response or radiographic progression. Further studies in larger patient materials are needed to understand the role of ACPA reactivities in patients with RA classified according to the 2010 ACR/EULAR criteria and treated according to modern treatment strategies.Trial registrationwww.ClinicalTrials.gov, NCT01205854. Registered on 21 September 2010.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1635-7) contains supplementary material, which is available to authorised users.

The Clinical Value of Autoantibodies in Rheumatoid Arthritis

“…Similarly, in the METEOR database including more than 1,800 patients with MTX as part of their initial treatment strategy, short-term remission in newly diagnosed RA was not affected by neither ACPA nor RF positivity (94). The analysis of ACPA reactivities does not seem to add much to prediction of treatment response, as recently shown in the context of the ARCTIC trial, were no difference in median baseline levels or number of ACPA reactivities was found between patients with different EULAR responses to MTX monotherapy (95).…”

Antibodies to synthetic citrullinated peptide epitope correlate with disease activity and flares in rheumatoid arthritis

“…ELISA was conducted following our published procedure [21]. RF positivity is a hallmark of over 50% of RA cases [5]. Besides, the commercial ACPA test (CCP2) was applied.…”

“…Furthermore, the presence of ACPA before the onset of RA symptoms can greatly advance understanding of disease pathogenesis. This knowledge may represent a milestone for early RA diagnosis and effective disease management [5].…”

“…[2][3][4][5]. ��� Other treatment included biological drugs adalimumab and infliximab for RA, and belimumab for SLE.https://doi.org/10.1371/journal.pone.0232010.t002…”

Screening and Verification of Key Proteins in Patients with Rheumatoid Arthritis and Intervention of Traditional Chinese Medicine

“…The emerging area of proteomics holds promise for biomarker discovery in complex diseases. Thus far proteomic methodologies have been applied to the study the biology of RA to only a very limited extent [3].…”