Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: Receptor activator of nuclear factor κB ligand (RANKL) an important regulator of bone metabolism has a key role in local bone destruction and osteoporosis in rheumatoid arthritis (RA). The aim of this study was to investigate the relationships between RANKL and biomarkers (anti-citrullinated peptide antibodies (ACPA), anti-carbamylated (anti-CarP) antibodies and cytokines) in individuals before symptom onset of RA and their association to radiological findings at disease onset.
Methods: A case-control study with 470 (334 women/136 men) pre-symptomatic individuals (mean age±SD 52.3±9.4) who had donated blood samples before symptom onset and 96 (60 women/36 men) population based controls was performed within the Medical Biobank of Northern Sweden. The median (IQR) predating time before symptom onset was 5 (5.1) years. Radiographs of hands and feet performed when diagnosed with RA were grade using Larsen score. ELISAs were used for analysing RANKL (BioVendor, Karasek, Czech Republic), anti-CCP2 antibodies (Eurodiagnostics, Sweden), anti-CarP antibodies (in-house ELISA in collaboration with L Trouw, NL) and ACPA using multiplex ISAC platform (PhaDia AB, Sweden) in plasma. Cytokines were analysed using Meso Scale Discovery V-plex methods (Maryland, USA). The cut-off for RANKL was set at 95% according to the ROC curve.
Results: The concentration of RANKL was significantly higher in the pre-symptomatic individuals compared with controls, mean±SEM 0.50±0.03 nmol/L versus 0.22±0.02 nmol/L, (p<0.001). The RANKL concentration increased gradually over time the closer to onset of symptoms samples were collected. Anti-CCP2 positive pre-symptomatic individuals had higher levels of RANKL compared with sero-negative individuals, as for rheumatoid factor positive individuals (p<0.001). Concentrations of RANKL were significantly associated with several ACPA specificities, anti-CarP antibodies, interleukin (IL)6 and IL10 concentrations in pre-symptomatic individuals. RANKL concentrations were related to higher Larsen score at RA diagnosis in men (p<0.05). Combination of positivity of RANKL and anti-CarP antibodies yielded increased risk for higher Larsen score at RA diagnosis compared with being negative for both as a reference, ß= 6.23 (95%Cl 0.96, 11.50, p<0.021).
Conclusion: RANKL concentrations were increased several years before symptom onset of RA and associated with Larsen score when RA was diagnosed in men. Combination of positivity of both RANKL and anti-CarP antibodies yielded the highest Larsen score at disease onset. These findings provide new insight into some of the key mechanism of RANKL in bone destruction in individuals already years before onset of symptoms of RA.
To cite this abstract in AMA style:Johansson L, Ärlestig L, Kokkonen H, Rantapaa-Dahlqvist S. Increased Concentration of Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) Predate Onset of Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/increased-concentration-of-receptor-activator-of-nuclear-factor-kappa-b-ligand-rankl-predate-onset-of-rheumatoid-arthritis/. Accessed March 26, 2019.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-concentration-of-receptor-activator-of-nuclear-factor-kappa-b-ligand-rankl-predate-onset-of-rheumatoid-arthritis/