An increased concentration of receptor activator of nuclear factor kappa-B ligand pre-dates the onset of rheumatoid arthritisVisa övriga samt affilieringar
2017 (Engelska)Ingår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 56, nr 12, s. 2190-2196Artikel i tidskrift (Refereegranskat) Published
Abstract [en]
Objectives: RANK ligand (RANKL) is involved in destruction and osteoporosis in RA. In this study, the relationships between RANKL and ACPA, anti-carbamylated protein antibodies (anti-CarP), cytokines and chemokines were analysed in individuals before the onset of RA symptoms, and their associations with radiological findings at disease onset were assessed.
Methods: This was a case-control study performed within the Medical Biobank of Northern Sweden that included 470 pre-symptomatic individuals [334 women and 136 men; mean (S.D.) age 52.3 (9.4) years] using blood samples donated before symptom onset (pre-dating time; 5.0 years) and 96 controls (60 women and 36 men). Plasma was analysed for RANKL (BioVendor, Karasek, Brno, Czech Republic), anti-CCP2 antibodies (Eurodiagnostics, Malmo, Sweden), anti-CarP antibodies (in-house ELISA), ACPA specificities (ISAC-platform, Phadia AB, Uppsala, Sweden) and cytokines/chemokines (Meso Scale Discovery methods, Rockville, MD, USA). Radiographs of hands and feet were graded using the Larsen score.
Results: The concentration of RANKL was higher in the pre-symptomatic individuals compared with controls; mean (S.E.M.): 0.50 (0.03) vs 0.22 (0.02) nmol/l (P < 0.001). The concentration increased gradually over time until symptom onset but appeared later than ACPA/RF/anti-CarP antibodies. Positivity for these antibodies yielded higher levels of RANKL compared with seronegativity (P < 0.001). RANKL concentrations were significantly associated with IL-6 and IL-10 concentrations. The combination of positivity for RANKL and anti-CarP antibodies resulted in a higher Larsen score at diagnosis beta = 6.18 (95% CI: 0.93, 11.43; P = 0.022).
Conclusion: RANKL concentrations were increased several years before symptom onset for RA, particularly in ACPA/RF/anti-CarP-positive individuals, all detectable earlier than RANKL. Positivity for RANKL and anti-CarP antibodies yielded the highest Larsen score at disease onset.
Ort, förlag, år, upplaga, sidor
Oxford University Press, 2017. Vol. 56, nr 12, s. 2190-2196
Nyckelord [en]
RANK ligand, ACPA, anti-CarP IgG, RA, pre-symptomatic individuals
Nationell ämneskategori
Reumatologi och inflammation
Identifikatorer
URN: urn:nbn:se:umu:diva-163051DOI: 10.1093/rheumatology/kex339ISI: 000416628500027PubMedID: 29029341Scopus ID: 2-s2.0-85038129437OAI: oai:DiVA.org:umu-163051DiVA, id: diva2:1350202
2019-09-112019-09-112023-03-24Bibliografiskt granskad