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Original article
Serum osteopontin: a biomarker of disease activity and predictor of relapsing course in patients with giant cell arteritis. Potential clinical usefulness in tocilizumab-treated patients
  1. Sergio Prieto-González1,
  2. Nekane Terrades-García1,
  3. Marc Corbera-Bellalta1,
  4. Ester Planas-Rigol1,
  5. Chie Miyabe2,
  6. Marco A Alba1,
  7. Ariel Ponce1,
  8. Itziar Tavera-Bahillo1,
  9. Giuseppe Murgia1,
  10. Georgina Espígol-Frigolé1,
  11. Javier Marco-Hernández1,
  12. José Hernández-Rodríguez1,
  13. Ana García-Martínez3,
  14. Sebastian H Unizony2 and
  15. Maria C Cid1
  1. 1Department of Autoimmune Diseases, Vasculitis Research Unit, University of Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CRB-CELLEX, Barcelona, Spain
  2. 2Division of Rheumatology, Allergy and Immunology, Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
  3. 3Department of Emergency Medicine, Hospital Clínic, University of Barcelona, IDIBAPS, CRB-CELLEX, Barcelona, Spain
  1. Correspondence to Dr Sergio Prieto-González; sprieto{at}clinic.ub.es and Dr Maria C Cid; mccid{at}clinic.ub.es

Abstract

Background Osteopontin (OPN) is a glycoprotein involved in Th1 and Th17 differentiation, tissue inflammation and remodelling. We explored the role of serum OPN (sOPN) as a biomarker in patients with giant cell arteritis (GCA).

Methods sOPN was measured by immunoassay in 76 treatment-naïve patients with GCA and 25 age-matched and sex-matched controls. In 36 patients, a second measurement was performed after 1 year of glucocorticoid treatment. Baseline clinical and laboratory findings, as well as relapses and glucocorticoid requirements during follow-up, were prospectively recorded. sOPN and C reactive protein (CRP) were measured in 32 additional patients in remission treated with glucocorticoids or tocilizumab (interleukin 6 (IL-6) receptor antagonist). In cultured temporal arteries exposed and unexposed to tocilizumab, OPN mRNA expression and protein production were measured by reverse transcription polymerase chain reaction (RT-PCR) and immunoassay, respectively.

Results sOPN concentration (ng/mL; mean±SD) was significantly elevated in patients with active disease (116.75±65.61) compared with controls (41.10±22.65; p<0.001). A significant decline in sOPN was observed in paired samples as patients entered disease remission (active disease 102.45±57.72, remission 46.47±23.49; p<0.001). sOPN correlated with serum IL-6 (r=0.55; p<0.001). Baseline sOPN concentrations were significantly higher in relapsing versus non-relapsing patients (relapsers 129.08±74.24, non-relapsers 90.63±41.02; p=0.03). OPN mRNA expression and protein production in cultured arteries were not significantly modified by tocilizumab. In tocilizumab-treated patients, CRP became undetectable, whereas sOPN was similar in patients in tocilizumab-maintained (51.91±36.25) or glucocorticoid-maintained remission (50.65±23.59; p=0.49).

Conclusions sOPN is a marker of disease activity and a predictor of relapse in GCA. Since OPN is not exclusively IL-6-dependent, sOPN might be a suitable disease activity biomarker in tocilizumab-treated patients.

  • giant cell arteritis
  • corticosteroids
  • cytokines
  • systemic vasculitis

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Footnotes

  • SP-G and NT-G contributed equally.

  • Contributors MCC had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study design: SP-G, NT-G, MCC. Acquisition of data: SP-G, NT-G, MC-B, CM, EP-R, AG-M, GE-F, IT-B, AP, JM-H, MAA, JH-R, SHU, MCC. Analysis and interpretation of data: SP-G, GE-F, MAA, MC-B, EP-R, JH-R, SHU, MCC. Manuscript preparation: SP-G, NT-G, SHU, MCC. Statistical analysis: SP-G, MAA, NT-G, MCC. All authors read, made improvements and approved the manuscript.

  • Funding Supported by Ministerio de Economía y Competitividad (SAF 14/57708-R and SAF17/82275-R), Marató TV3 (201507), Instituto de Salud Carlos III (PIE13/00033) and Fondo Europeo de Desarrollo Regional (FEDER, una manera de hacer Europa). SP-G and IT-B were supported by a research award from Hospital Clínic, GE-F by Instituto de Salud Carlos III (PI 15/00092), and MAA by Consejo Nacional de Ciencia y Tecnología (CONACyT), Mexico, and by Agencia de Gestió d’Ajuts Universitaris i de Recerca (AGAUR), Generalitat de Catalunya.

  • Competing interests GE-F, SP-G, JH-R, SHU and MCC have participated in the GiACTA trial sponsored by Hoffmann-La Roche. MCC has received consultation fees from Hoffman-La Roche.

  • Ethics approval The study was approved by the ethics committee of Hospital Clínic (Barcelona, Spain) and the Massachusetts General Hospital (Boston, Massachussets, USA).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data are available.

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