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An increased concentration of receptor activator of nuclear factor kappa-B ligand pre-dates the onset of rheumatoid arthritis
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.ORCID iD: 0000-0001-7675-3488
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2017 (English)In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 56, no 12, p. 2190-2196Article in journal (Refereed) 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.

Place, publisher, year, edition, pages
Oxford University Press, 2017. Vol. 56, no 12, p. 2190-2196
Keywords [en]
RANK ligand, ACPA, anti-CarP IgG, RA, pre-symptomatic individuals
National Category
Rheumatology and Autoimmunity
Identifiers
URN: urn:nbn:se:umu:diva-163051DOI: 10.1093/rheumatology/kex339ISI: 000416628500027PubMedID: 29029341OAI: oai:DiVA.org:umu-163051DiVA, id: diva2:1350202
Available from: 2019-09-11 Created: 2019-09-11 Last updated: 2019-09-11Bibliographically approved

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Johansson, LindaÄrlestig, LisbethKokkonen, HeidiBrink, MikaelRantapää-Dahlqvist, Solbritt

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