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Objective <p>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).</p> Methods <p>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.</p> Results <p>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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月2日

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  • Chiara Baggio,
  • Luca Iorio,
  • Carlotta Boscaro,
  • Federica Davanzo,
  • Veronica Davanzo,
  • Michela Pelloso,
  • Marta Tonello,
  • Paolo Sfriso,
  • Mattia Albiero,
  • Roberta Ramonda,
  • Andrea Doria,
  • Roberto Padoan,
  • Francesca Oliviero

摘要

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.