Abstract

IntroductionAutoantibodies against citrullinated peptides/proteins (ACPA) are found in approximately 75% of the sera of patients with rheumatoid arthritis (RA). The RA-specific ACPA are frequently present prior to disease onset and their presence associates with a more erosive disease course. ACPA can therefore be used to aid the diagnosis and prognosis of RA. Recently, it became clear that ACPA are very heterogeneous, both in an individual patient and among different patients. The aim of this study was to investigate whether clinically meaningful ACPA profiles exist in early RA patients.MethodsTwenty citrullinated peptides and the corresponding non-citrullinated control peptides were immobilized on microarray sensor chips. Sera from 374 early arthritis patients were analyzed by surface plasmon resonance imaging (iSPR) of biomolecular interactions on the sensor chip.ResultsCluster analysis of the reactivities with the citrullinated peptides, after subtraction of the reactivities with the corresponding control peptides confirmed the heterogeneity of the ACPA response in RA and revealed 12 distinct ACPA profiles. The association of the 5 most frequent profiles with clinical features at diagnosis and during the disease course was examined, showing no statistically significant associations.ConclusionsCompared to the detection of ACPA in RA sera by CCP-based assays, ACPA profiling in early arthritis patients did not reveal associations with disease activity and progression scores.

Highlights

  • Autoantibodies against citrullinated peptides/proteins (ACPA) are found in approximately 75% of the sera of patients with rheumatoid arthritis (RA)

  • Sera from 374 early arthritis patients were analyzed by surface plasmon resonance imaging of biomolecular interactions on the sensor chip

  • Cluster analysis of the reactivities with the citrullinated peptides, after subtraction of the reactivities with the corresponding control peptides confirmed the heterogeneity of the Anticitrullinated protein antibody (ACPA) response in RA and revealed 12 distinct ACPA profiles

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Summary

Introduction

Autoantibodies against citrullinated peptides/proteins (ACPA) are found in approximately 75% of the sera of patients with rheumatoid arthritis (RA). Just about all ACPAs are reactive in the CCP2 test, diverse reactivity is observed when other citrullinated molecules are used, for example, peptides derived from fibrinogen and vimentin [14]. This indicates that the ACPA response in RA is heterogeneous, with diverse patterns of reactivity to distinct citrullinated epitopes. RA patients are classified into two distinct groups: anti-CCP2-positive and anti-CCP2-negative It remains to be investigated whether the ACPA fine specificity may improve van Beers et al Arthritis Research & Therapy 2013, 15:R140 http://arthritis-research.com/content/15/5/R140 diagnosis and/or prognosis [15,16]. It is interesting to note that low and intermediate pretreatment levels of ACPA appear to be associated with a more favorable response to methotrexate treatment in recent onset anti-CCP-positive arthritis, whereas high levels are associated with an insufficient response [17]

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