Development of a highly sensitive chemiluminescence immunoassay for quantification of aggrecanase-generated ARGS aggrecan fragments in serum.
Osteoarthr Cartil Open
; 3(2): 100162, 2021 Jun.
Article
em En
| MEDLINE
| ID: mdl-36474987
ABSTRACT
Objective:
Cartilage degradation is a hallmark of osteoarthritis (OA). Aggrecan, a major proteoglycan of articular cartilage extracellular matrix (ECM), is degraded by ADAMTS-5 resulting in the release of ARGS-G2 fragments to synovial fluid and circulation. The aim was to quantify ARGS-G2 in the serum of OA patients using the huARGS immunoassay.Methods:
The immunoassay was produced under GMP conditions and the technical performance was assessed. The biological relevance of the immunoassay was assessed in the conditioned media from a bovine full-depth cartilage explant (BEX) model. The diurnal and inter-day variations of ARGS levels were evaluated in OA patients' serum. Post-hoc analysis of huARGS was conducted in a sub-cohort of a phase III OA trial testing the safety and efficacy of oral salmon calcitonin.Results:
Technical performance huARGS demonstrated good technical performance. Biological relevance ARGS release was induced by inflamatory facotrs stimulation compared to the vehicle group, reaching a peak at day 3 and gradually decreasing to base level at day 12. The ARGS release was suppressed by the addition of the ADAMTS-4/-5 activation inhibitor. Biological variation No significant diurnal or inter-day effect was found. Phase III clinical trial The participants in the lowest group (Q1) of baseline huARGS levels were more likely to progress radiographically than the highest group (Q4) OR 3.38[0.81-14.02].Conclusions:
The huARGS shows good technical performance and low biological variation. It has the potential to aid drug development in various stages, both as a PD biomarker and identifying progressors who might be likely to respond to an OA drug.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Diagnostic_studies
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article