title: MRI-detected osteitis is not associated with the presence or level of ACPA alone, but with the combined presence of ACPA and RF.
abstract: In 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).
  
  
  
  Disease-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.
  
  
  
  In 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.
  
  
  
  The 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.
authors.affiliation: Department of Rheumatology C1-R, Leiden University Medical Center, PO Box 9600, Leiden, 2300, RC, The Netherlands. D.M.Boeters@lumc.nl.
authors.forename: Debbie M
authors.initials: DM
authors.lastname: Boeters
authors.affiliation: Department of Rheumatology C1-R, Leiden University Medical Center, PO Box 9600, Leiden, 2300, RC, The Netherlands.
authors.forename: Wouter P
authors.initials: WP
authors.lastname: Nieuwenhuis
authors.affiliation: Department of Rheumatology C1-R, Leiden University Medical Center, PO Box 9600, Leiden, 2300, RC, The Netherlands.
authors.forename: Marije K
authors.initials: MK
authors.lastname: Verheul
authors.affiliation: Department of Rheumatology C1-R, Leiden University Medical Center, PO Box 9600, Leiden, 2300, RC, The Netherlands.
authors.forename: Elize C
authors.initials: EC
authors.lastname: Newsum
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: Reijnierse
authors.affiliation: Department of Rheumatology C1-R, Leiden University Medical Center, PO Box 9600, Leiden, 2300, RC, The Netherlands.
authors.forename: René E M
authors.initials: RE
authors.lastname: Toes
authors.affiliation: Department of Rheumatology C1-R, Leiden University Medical Center, PO Box 9600, Leiden, 2300, RC, The Netherlands.
authors.forename: Leendert A
authors.initials: LA
authors.lastname: Trouw
authors.affiliation: Department of Rheumatology C1-R, Leiden University Medical Center, PO Box 9600, Leiden, 2300, RC, The Netherlands.
authors.forename: Annette H M
authors.initials: AH
authors.lastname: van der Helm-van Mil
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000000981:diagnostic imaging / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010000:Osteitis / Q000276:immunology*; D010456:Peptides, Cyclic / Q000276:immunology*; D012217:Rheumatoid Factor / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor
keywords: ACPA; Bone marrow edema; MRI; RF; Rheumatoid arthritis