Serum proteomics in giant cell arteritis in response to a three-day pulse of glucocorticoid followed by tocilizumab monotherapy (the GUSTO trial).

Autor:	Christ L; Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Gloor AD; Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Kollert F; Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland., Gaber T; Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany., Buttgereit F; Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany., Reichenbach S; Department of Rheumatology and Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.; University of Bern, Institute for Social and Preventive Medicine, Bern, Switzerland., Villiger PM; Medical Center Monbijou, Rheumatology and Immunology, Bern, Switzerland.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 May 23; Vol. 14, pp. 1165758. Date of Electronic Publication: 2023 May 23 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1165758
Abstrakt:	Objective: Proteome analyses in patients with newly diagnosed, untreated giant cell arteritis (GCA) have not been reported previously, nor are changes of protein expression upon treatment with glucocorticoids (GC) and/or tocilizumab (TCZ) known. The GUSTO trial allows to address these questions, provides the opportunity to learn about the differential effects of GC and TCZ on proteomics and may help to identify serum proteins to monitor disease activity. Methods: Serum samples obtained from 16 patients with new-onset GCA at different time points (day 0, 3, 10, and week 4, 24, 52) during the GUSTO trial (NCT03745586) were examined for 1436 differentially expressed proteins (DEPs) based on proximity extension assay technology. The patients received 500 mg methylprednisolone intravenously for 3 consecutive days followed by TCZ monotherapy. Results: When comparing day 0 (before the first GC infusion) with week 52 (lasting remission), 434 DEPs (213↑, 221↓) were identified. In response to treatment, the majority of changes occurred within 10 days. GC inversely regulated 25 proteins compared to remission. No difference was observed between weeks 24 and 52 during established remission and ongoing TCZ treatment. Expression of CCL7, MMP12, and CXCL9 was not regulated by IL6. Conclusion: Disease-regulated serum proteins improved within 10 days and were normalized within 24 weeks, showing a kinetic corresponding to the gradual achievement of clinical remission. The proteins inversely regulated by GC and TCZ shed light on the differential effects of the two drugs. CCL7, CXCL9, and MMP12 are biomarkers that reflect disease activity despite normalized C-reactive protein levels. Competing Interests: LC reports research/non-financial support, advisory fee and stock ownership from Gilead Sciences, F. Hoffmann-La Roche, Novartis, Pfizer, Bristol-Myers Squibb, and Sanofi. FB has received consultancy fees, honoraria and travel expenses from Abbvie, Galapagos, Novartis, Pfizer, Roche, and Sanofi, all unrelated to this manuscript. FK is a shareholder of Roche, was a consultant of Actelion, BMS, Boehringer-Ingelheim, and Pfizer, has grant/research support from Gilead, Pfizer and Roche, and is currently employed by Roche. PV has received consultancy fees, honoraria and travel expenses from F. Hoffmann-La Roche, MSD, Abbvie, Pfizer, Grünenthal, Amgen, Bristol-Myers Squibb, and Janssen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest. (Copyright © 2023 Christ, Gloor, Kollert, Gaber, Buttgereit, Reichenbach and Villiger.)
Databáze:	MEDLINE
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