PMID- 35973802 OWN - NLM STAT- MEDLINE DCOM- 20230125 LR - 20240412 IS - 1468-2060 (Electronic) IS - 0003-4967 (Linking) VI - 82 IP - 2 DP - 2023 Feb TI - Association of baseline soluble immune checkpoints with the risk of relapse in PR3-ANCA vasculitis following induction of remission. PG - 253-261 LID - 10.1136/ard-2022-222479 [doi] AB - 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. CI - (c) Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Gamerith, Gabriele AU - Gamerith G AD - Department of Internal Medicine V, Hematology and Oncology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck, Innsbruck, Austria. FAU - Mildner, Finn AU - Mildner F AD - Department of Internal Medicine V, Hematology and Oncology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck, Innsbruck, Austria. FAU - Merkel, Peter A AU - Merkel PA AD - Division of Rheumatology and Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Harris, Kristina AU - Harris K AD - Immune Tolerance Network (ITN), Bethesda, Maryland, USA. FAU - Cooney, Laura AU - Cooney L AD - Immune Tolerance Network (ITN), Bethesda, Maryland, USA. FAU - Lim, Noha AU - Lim N AD - Immune Tolerance Network (ITN), Bethesda, Maryland, USA. FAU - Spiera, Robert AU - Spiera R AUID- ORCID: 0000-0003-2911-6800 AD - Hospital for Special Surgery, New York City, New York, USA. FAU - Seo, Philip AU - Seo P AD - Department of Internal Medicine, Division of Rheumatology, Johns Hopkins University, Baltimore, Maryland, USA. FAU - Langford, Carol A AU - Langford CA AD - Rheumatic and Immunologic Diseases, Cleveland Clinic Foundation, Cleveland, Ohio, USA. FAU - Hoffman, Gary S AU - Hoffman GS AD - Rheumatic and Immunologic Diseases, Cleveland Clinic Foundation, Cleveland, Ohio, USA. FAU - St Clair, E William AU - St Clair EW AD - Rheumatology, Duke University School of Medicine, Durham, North Carolina, USA. FAU - Fervenza, Fernando C AU - Fervenza FC AD - Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA. FAU - Monach, Paul AU - Monach P AD - VA Boston Healthcare System, West Roxbury, Massachusetts, USA. FAU - Ytterberg, Steven R AU - Ytterberg SR AD - Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Geetha, Duvuru AU - Geetha D AUID- ORCID: 0000-0001-8353-5542 AD - Division of Nephrology, Johns Hopkins University, Baltimore, Maryland, USA. FAU - Amann, Arno AU - Amann A AD - Department of Internal Medicine V, Hematology and Oncology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck, Innsbruck, Austria. FAU - Wolf, Dominik AU - Wolf D AD - Department of Internal Medicine V, Hematology and Oncology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck, Innsbruck, Austria. FAU - Specks, Ulrich AU - Specks U AD - Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, New York, USA. FAU - Stone, John H AU - Stone JH AUID- ORCID: 0000-0001-6588-9435 AD - Rheumatology Unit, Division of Rheumatology Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Kronbichler, Andreas AU - Kronbichler A AUID- ORCID: 0000-0002-2945-2946 AD - Department of Medicine, University of Cambridge, Cambridge, UK ak2283@cam.ac.uk. LA - eng GR - UM1 AI109565/AI/NIAID NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial DEP - 20220816 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 0 (Antibodies, Antineutrophil Cytoplasmic) RN - EC 3.4.21.76 (Myeloblastin) RN - 4F4X42SYQ6 (Rituximab) SB - IM MH - Humans MH - *Antibodies, Antineutrophil Cytoplasmic MH - Myeloblastin MH - Rituximab/therapeutic use MH - Remission Induction MH - *Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy MH - Recurrence OTO - NOTNLM OT - autoimmune diseases OT - rituximab OT - systemic vasculitis COIS- Competing interests: None declared. EDAT- 2022/08/17 06:00 MHDA- 2023/01/26 06:00 CRDT- 2022/08/16 21:13 PHST- 2022/03/15 00:00 [received] PHST- 2022/08/02 00:00 [accepted] PHST- 2022/08/17 06:00 [pubmed] PHST- 2023/01/26 06:00 [medline] PHST- 2022/08/16 21:13 [entrez] AID - ard-2022-222479 [pii] AID - 10.1136/ard-2022-222479 [doi] PST - ppublish SO - Ann Rheum Dis. 2023 Feb;82(2):253-261. doi: 10.1136/ard-2022-222479. Epub 2022 Aug 16.