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Immature leukocyte and plasma-induced cell death reveal subclinical immune activation in EGPA patients in remission

Title: Immature leukocyte and plasma-induced cell death reveal subclinical immune activation in EGPA patients in remission
Authors: Baggio C.; Iorio L.; Boscaro C.; Davanzo F.; Davanzo V.; Pelloso M.; Tonello M.; Sfriso P.; Albiero M.; Ramonda R.; Doria A.; Padoan R.; Oliviero F.
Contributors: Baggio, C.; Iorio, L.; Boscaro, C.; Davanzo, F.; Davanzo, V.; Pelloso, M.; Tonello, M.; Sfriso, P.; Albiero, M.; Ramonda, R.; Doria, A.; Padoan, R.; Oliviero, F.
Publisher Information: SPRINGER BASEL AG
Publication Year: 2026
Collection: Padua Research Archive (IRIS - Università degli Studi di Padova)
Subject Terms: ANCA-associated vasculiti; Cytology; Eosinophilic granulomatosis with polyangiiti; Inflammasome; Innate immune cell; Neutrophils
Description: Objective: ANCA-associated vasculitis (AAV) is a group of rare autoimmune diseases characterized by pauci-immune necrotizing inflammation of small to medium-sized blood vessels, in which ANCAs targeting neutrophil antigens promote neutrophil activation, endothelial injury and organ damage. Although AAV follows a relapsing-remitting course, the immune landscape during remission remains poorly defined. This study investigated leukocyte alterations across AAV subtypes and examined whether plasma from ANCA-positive and ANCA-negative eosinophilic granulomatosis with polyangiitis (EGPA) patients in remission modulates peripheral blood mononuclear cell (PBMC) responses in healthy donors (HDs). Methods: Peripheral blood was collected from 62 AAV patients in remission and 28 age- and sex-matched HDs. Leukocyte morphology was assessed via May-Grünwald Giemsa staining. Circulating cytokines and chemokines were quantified by ELISA. HD-derived PBMCs were exposed to plasma from EGPA patients, antiphospholipid-positive controls, or HDs. Cell death, metabolic activity, and cytokine production were evaluated using Trypan Blue, Annexin V/PI staining, MTT assays, and ELISA. Chemotaxis assays assessed cell migration in response to conditioned media, with or without Anakinra or CCR1 inhibitor J113863. Results: AAV patients showed increased immature neutrophils. Plasma from ANCA-positive EGPA patients induced PBMC death, inflammasome-related cytokine release, and secretion of chemotactic and proangiogenic factors. Conditioned media enhanced immune cell migration in a cytokine-dependent manner. Conclusion: These findings indicate persistent subclinical immune activation during AAV remission, particularly in ANCA-positive EGPA, suggesting a role for mononuclear cell-mediated inflammation in relapse risk and the potential utility of immune monitoring.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/41622325; info:eu-repo/semantics/altIdentifier/wos/WOS:001676038600003; volume:75; issue:1; journal:INFLAMMATION RESEARCH; https://hdl.handle.net/11577/3582450
DOI: 10.1007/s00011-026-02189-7
Availability: https://hdl.handle.net/11577/3582450; https://doi.org/10.1007/s00011-026-02189-7; https://link.springer.com/article/10.1007/s00011-026-02189-7
Rights: info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.B3D9F7DF
Database: BASE