In Contrast to Anti-CCP, MMP-Degraded and Citrullinated Vimentin (VICM) Is Both a Diagnostic and a Treatment Response Biomarker

Autor:	Patryk J. Drobinski, Neel I. Nissen, Dovile Sinkeviciute, Nicholas Willumsen, Morten A. Karsdal, Anne C. Bay-Jensen
Rok vydání:	2022
Předmět:	rheumatoid arthritis autoimmunity Organic Chemistry biomarkers General Medicine vimentin low disease activity pharmacodynamics anti-CCP Catalysis Computer Science Applications Inorganic Chemistry Physical and Theoretical Chemistry Molecular Biology Spectroscopy
Zdroj:	International Journal of Molecular Sciences; Volume 24; Issue 1; Pages: 321 Drobinski, P J, Nissen, N I, Sinkeviciute, D, Willumsen, N, Karsdal, M A & Bay-Jensen, A C 2023, ' In Contrast to Anti-CCP, MMP-Degraded and Citrullinated Vimentin (VICM) Is Both a Diagnostic and a Treatment Response Biomarker ', International Journal of Molecular Sciences, vol. 24, no. 1, 321 . https://doi.org/10.3390/ijms24010321
ISSN:	1422-0067
Popis:	Protein citrullination and degradation by matrix metalloproteinases (MMP) plays a central role in the pathology of rheumatoid arthritis (RA). Autoantibodies are known to target citrullinated vimentin. The aim of this study was to investigate the relationship between the blood levels of MMP-degraded and citrullinated vimentin (VICM), as compared with the levels of MMP-degraded and non-citrullinated vimentin (VIM), and the standard anti-CCP biomarker in RA patients undergoing treatment. Thus, VIM, VICM and anti-CCP were quantified by ELISA in serum samples from baseline and week 8 of patients (n = 257) with RA, treated with either tocilizumab (8 mg/kg), methotrexate (7.5–15 mg/kg) or a placebo and compared with a reference cohort (n = 64). The three biomarkers were elevated in RA serum compared with the reference cohort: medians were 1.7 vs. 0.8 ng/mL (p < 0.05) for VIM; 7.5 vs. 0.7 ng/mL (p < 0.0001) for VICM; 57 vs. 4 RU/mL (p < 0.001) for anti-CCP. VICM was decreased in response to tocilizumab (2.9-fold, p < 0.0001) and to methotrexate (1.5-fold, p < 0.05) compared with the placebo, while anti-CCP was not. Serum VIM was also modulated by both drugs, although to a lesser degree. A high baseline level of VICM was predictive of a low disease activity response at week 8. In conclusion, VICM can differentiate between RA and healthy donors in a similar manner to anti-CCP; furthermore, VICM is also a pharmacodynamic marker.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::394c4bc2a1136a67e0186bd7db552727 https://pubmed.ncbi.nlm.nih.gov/36613765 Zobrazit plný text záznamu