Abstract

BackgroundIn rheumatoid arthritis (RA) bone marrow edema (BME, osteitis) and anti-citrullinated protein antibodies (ACPA) are associated with radiographic progression. ACPA have been associated with BME, but it is unknown if this association is confined to ACPA and BME. We performed cross-sectional analysis of the association of ACPA, rheumatoid factor (RF) and anti-carbamylated protein (anti-CarP) antibodies with BME and other types of inflammation (synovitis, tenosynovitis) detected by magnetic resonance imaging (MRI).MethodsDisease-modifying antirheumatic drug (DMARD)-naïve patients with early arthritis (n = 589), included in the Leiden Early Arthritis Clinic cohort, underwent contrast-enhanced 1.5 T MRI of unilateral wrist, metacarpophalangeal and metatarsophalangeal-joints at baseline. BME, synovitis and tenosynovitis were scored by two readers. ACPA, rheumatoid factor (RF) and anti-CarP were determined at baseline.ResultsIn univariable analyses ACPA-positive patients had higher BME scores than ACPA-negative patients (median 4.5 vs. 2.0, p < 0.001), but not more synovitis and tenosynovitis. Also RF (median 3.75 vs. 2.0, p < 0.001) and anti-CarP antibodies (median 3.5 vs. 2.5, p = 0.012) were associated with higher BME scores. Because the autoantibodies were concomitantly present, analyses were stratified for the presence of different autoantibody combinations. ACPA-positive (ACPA+), RF-negative (RF-), anti-CarP-negative (anti-CarP-) patients did not have higher BME-scores than ACPA-negative (ACPA-), RF-, anti-CarP- patients. However ACPA+, RF-positive (RF+), anti-CarP- patients and ACPA+, RF+, anti-CarP-positive (anti-CarP+) patients had higher BME scores than ACPA-, RF-, anti-CarP- patients (median 5.0 and 4.5 vs. 2.0, p < 0.001 and p < 0.001). ACPA levels were not associated with BME scores. Analyses within RA- and UA-patients revealed similar results.ConclusionsThe presence of ACPA alone or ACPA level was not statistically significantly associated with BME scores, but the combined presence of ACPA and RF was associated with more BME. This suggests an additive role of RF to ACPA in mediating osteitis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1076-0) contains supplementary material, which is available to authorized users.

Highlights

  • In rheumatoid arthritis (RA) bone marrow edema (BME, osteitis) and anti-citrullinated protein antibodies (ACPA) are associated with radiographic progression

  • ACPA is associated with BME at baseline We first evaluated whether patients with ACPA (n = 141) or without ACPA (n = 448) had differences in BME scores (Fig. 1a)

  • Similar results were obtained for BME when only patients with RA and undifferentiated arthritis (UA) were studied (ACPA-positive median = 3.5, ACPA-negative median = 2.0, p = 0.001) and no statistically significant differences were observed for synovitis and tenosynovitis (Additional file 2: Figure S1A)

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Summary

Introduction

In rheumatoid arthritis (RA) bone marrow edema (BME, osteitis) and anti-citrullinated protein antibodies (ACPA) are associated with radiographic progression. We performed cross-sectional analysis of the association of ACPA, rheumatoid factor (RF) and anti-carbamylated protein (anti-CarP) antibodies with BME and other types of inflammation (synovitis, tenosynovitis) detected by magnetic resonance imaging (MRI). Whereas synovitis and tenosynovitis can be evaluated by other imaging modalities, such as ultrasound, MRI is the only modality that depicts bone marrow edema (BME). These data suggest a link between BME and structural damage in RA. The importance of BME is supported by several studies showing that BME is a predictor of radiographic evidence of progression [5,6,7,8,9,10,11,12,13]. A recent study even showed that the persisting presence of BME is associated with an odds ratio (OR) of 60 for erosive progression at the same location [14]

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