An increased concentration of receptor activator of nuclear factor kappa-B ligand pre-dates the onset of rheumatoid arthritis
Autor: | Lisbeth Ärlestig, Mikael Brink, Linda Johansson, Solbritt Rantapää-Dahlqvist, Heidi Kokkonen |
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Rok vydání: | 2017 |
Předmět: |
Adult
Male musculoskeletal diseases 0301 basic medicine medicine.medical_treatment Osteoporosis Prodromal Symptoms Peptides Cyclic Anti-Citrullinated Protein Antibodies Arthritis Rheumatoid 03 medical and health sciences 0302 clinical medicine Rheumatology Rheumatoid Factor medicine Humans Pharmacology (medical) Receptor Autoantibodies Biological Specimen Banks Sweden 030203 arthritis & rheumatology biology Interleukin-6 Activator (genetics) business.industry RANK Ligand Middle Aged medicine.disease Interleukin-10 030104 developmental biology Cytokine RANKL Case-Control Studies Rheumatoid arthritis biology.protein Cancer research Female sense organs Antibody business |
Zdroj: | Rheumatology. 56:2190-2196 |
ISSN: | 1462-0332 1462-0324 |
Popis: | 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.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, Malmö, 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.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 (P0.001). 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 (P0.001). 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 β = 6.18 (95% CI: 0.93, 11.43; P = 0.022).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. |
Databáze: | OpenAIRE |
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