Association of baseline soluble immune checkpoints with the risk of relapse in PR3-ANCA vasculitis following induction of remission.

Autor:	Gamerith G; Department of Internal Medicine V, Hematology and Oncology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck, Innsbruck, Austria., Mildner F; Department of Internal Medicine V, Hematology and Oncology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck, Innsbruck, Austria., Merkel PA; Division of Rheumatology and Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Harris K; Immune Tolerance Network (ITN), Bethesda, Maryland, USA., Cooney L; Immune Tolerance Network (ITN), Bethesda, Maryland, USA., Lim N; Immune Tolerance Network (ITN), Bethesda, Maryland, USA., Spiera R; Hospital for Special Surgery, New York City, New York, USA., Seo P; Department of Internal Medicine, Division of Rheumatology, Johns Hopkins University, Baltimore, Maryland, USA., Langford CA; Rheumatic and Immunologic Diseases, Cleveland Clinic Foundation, Cleveland, Ohio, USA., Hoffman GS; Rheumatic and Immunologic Diseases, Cleveland Clinic Foundation, Cleveland, Ohio, USA., St Clair EW; Rheumatology, Duke University School of Medicine, Durham, North Carolina, USA., Fervenza FC; Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA., Monach P; VA Boston Healthcare System, West Roxbury, Massachusetts, USA., Ytterberg SR; Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, USA., Geetha D; Division of Nephrology, Johns Hopkins University, Baltimore, Maryland, USA., Amann A; Department of Internal Medicine V, Hematology and Oncology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck, Innsbruck, Austria., Wolf D; Department of Internal Medicine V, Hematology and Oncology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck, Innsbruck, Austria., Specks U; Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, New York, USA., Stone JH; Rheumatology Unit, Division of Rheumatology Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Kronbichler A; Department of Medicine, University of Cambridge, Cambridge, UK ak2283@cam.ac.uk.
Jazyk:	angličtina
Zdroj:	Annals of the rheumatic diseases [Ann Rheum Dis] 2023 Feb; Vol. 82 (2), pp. 253-261. Date of Electronic Publication: 2022 Aug 16.
DOI:	10.1136/ard-2022-222479
Abstrakt:	Objectives: We investigated whether soluble immune checkpoints (sICPs) predict treatment resistance, relapse and infections in patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). Methods: Plasma sICP concentrations from available samples obtained during conduct of the RAVE trial were measured by immunoabsorbent assays from patients with either proteinase 3 (PR3) or myeloperoxidase (MPO)-ANCA vasculitis and were correlated with clinical outcomes, a set of biomarkers and available flow cytometry analyses focusing on T cell subsets. Log-rank test was used to evaluate survival benefits, and optimal cut-off values of the marker molecules were calculated using Yeldons J. Results: Analysis of 189 plasma samples at baseline revealed higher concentrations of sTim-3, sCD27, sLag-3, sPD-1 and sPD-L2 in patients with MPO-ANCA vasculitis (n=62) as compared with PR3-ANCA vasculitis (n=127). Among patients receiving rituximab induction therapy (n=95), the combination of lower soluble (s)Lag-3 (<90 pg/mL) and higher sCD27 (>3000 pg/mL) predicted therapy failure. Twenty-four out of 73 patients (32.9%) in the rituximab arm reaching remission at 6 months relapsed during follow-up. In this subgroup, high baseline values of sTim-3 (>1200 pg/mL), sCD27 (>1250 pg/mL) and sBTLA (>1000 pg/mL) were associated with both sustained remission and infectious complications. These findings could not be replicated in 94 patients randomised to receive cyclophosphamide/azathioprine. Conclusions: Patients with AAV treated with rituximab achieved remission less frequently when concentrations of sLag-3 were low and concentrations of sCD27 were high. Higher concentrations of sTim-3, sCD27 and sBTLA at baseline predicted relapse in patients treated with rituximab. These results require confirmation but may contribute to a personalised treatment approach of AAV. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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