Immune Cell Subsets in ANCA-Associated Vasculitis
(2026) In Lund University, Faculty of Medicine Doctoral Dissertation Series- Abstract
- Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are rare autoimmune diseases, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophil granulomatosis with polyangiitis (EGPA). They are three distinct diseases with overlapping symptoms and signs. The ANCAs involved in AAV are mainly directed against myeloperoxidase (MPO) and proteinase 3 (PR3), found in neutrophils and monocytes. The pathogenesis is multifactorial and include genetic and environmental factors e.g. infections.
Adult patients with AAV diagnosis were recruited at the time of diagnosis or later when referred to the outpatient clinics of Nephrology or Rheumatology, Skåne University Hospital, Lund Sweden. ... (More) - Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are rare autoimmune diseases, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophil granulomatosis with polyangiitis (EGPA). They are three distinct diseases with overlapping symptoms and signs. The ANCAs involved in AAV are mainly directed against myeloperoxidase (MPO) and proteinase 3 (PR3), found in neutrophils and monocytes. The pathogenesis is multifactorial and include genetic and environmental factors e.g. infections.
Adult patients with AAV diagnosis were recruited at the time of diagnosis or later when referred to the outpatient clinics of Nephrology or Rheumatology, Skåne University Hospital, Lund Sweden. Patients were classified into GPA, MPA or EGPA according to the consensus methodology by Watts et al in 2007 and the American College of Rheumatology (ACR) criteria. The patient blood samples were collected between 2011 and 2020. Healthy blood donors (HC) were used as controls. Immunophenotyping and function of immune cells were performed by flow cytometry analyses. The aim was to investigate correlations between various cell subsets and cellular functions with disease activity, propensity for relapse, and response to rituximab treatment.
In paper I, we identified significant alterations in the B-cell compartment, characterized by reduced frequencies of total B cells and transitional B cells, alongside increased switched memory B cells, plasmablasts and activated B cells in AAV patients compared to healthy controls. The immunoglobulin levels were within normal range.
In paper II, we report increased neutrophil and monocyte subpopulations in AAV patients compared to HC but decreased classical monocytes in MPA patients compared to GPA. During active disease we observed higher concentration of mature neutrophils and decreased total and intermediate monocytes. Moreover, rituximab treatment may influence intermediate and classical monocytes frequencies.
In paper III, we observed decreased phagocytic capacity and alterations to generate reactive oxygen species, related to ANCA subtype, rituximab treatment, and infections.
Findings from the studies included in this thesis highlight the important role of immune cells in the pathogenesis and clinical outcome of ANCA-associated vasculitis. However, a clear and comprehensive understanding of the immune cell alterations involved in AAV is still lacking, warranting further investigation.
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Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/035233c3-6f2d-4722-a9ad-ad8d8e2df315
- author
- Smargianaki, Sofia LU
- supervisor
- opponent
-
- Associate Professor Hultgren, Olof, Department of Clinical Immunology and Transfusion Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
- organization
- publishing date
- 2026
- type
- Thesis
- publication status
- published
- subject
- keywords
- ANCA associated vasculitis, GPA, MPA, B-cell, granulocytes, neutrophils, monocytes
- in
- Lund University, Faculty of Medicine Doctoral Dissertation Series
- issue
- 2026:29
- pages
- 84 pages
- publisher
- Lund University, Faculty of Medicine
- defense location
- Föreläsningssal 2, Centralblocket, Entrégatan 7, Skånes Universitetssjukhus i Lund
- defense date
- 2026-03-13 09:00:00
- ISSN
- 1652-8220
- ISBN
- 978-91-8021-827-6
- language
- English
- LU publication?
- yes
- id
- 035233c3-6f2d-4722-a9ad-ad8d8e2df315
- date added to LUP
- 2026-02-20 15:31:48
- date last changed
- 2026-02-24 09:40:45
@phdthesis{035233c3-6f2d-4722-a9ad-ad8d8e2df315,
abstract = {{Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are rare autoimmune diseases, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophil granulomatosis with polyangiitis (EGPA). They are three distinct diseases with overlapping symptoms and signs. The ANCAs involved in AAV are mainly directed against myeloperoxidase (MPO) and proteinase 3 (PR3), found in neutrophils and monocytes. The pathogenesis is multifactorial and include genetic and environmental factors e.g. infections. <br/>Adult patients with AAV diagnosis were recruited at the time of diagnosis or later when referred to the outpatient clinics of Nephrology or Rheumatology, Skåne University Hospital, Lund Sweden. Patients were classified into GPA, MPA or EGPA according to the consensus methodology by Watts et al in 2007 and the American College of Rheumatology (ACR) criteria. The patient blood samples were collected between 2011 and 2020. Healthy blood donors (HC) were used as controls. Immunophenotyping and function of immune cells were performed by flow cytometry analyses. The aim was to investigate correlations between various cell subsets and cellular functions with disease activity, propensity for relapse, and response to rituximab treatment. <br/>In paper I, we identified significant alterations in the B-cell compartment, characterized by reduced frequencies of total B cells and transitional B cells, alongside increased switched memory B cells, plasmablasts and activated B cells in AAV patients compared to healthy controls. The immunoglobulin levels were within normal range. <br/>In paper II, we report increased neutrophil and monocyte subpopulations in AAV patients compared to HC but decreased classical monocytes in MPA patients compared to GPA. During active disease we observed higher concentration of mature neutrophils and decreased total and intermediate monocytes. Moreover, rituximab treatment may influence intermediate and classical monocytes frequencies.<br/>In paper III, we observed decreased phagocytic capacity and alterations to generate reactive oxygen species, related to ANCA subtype, rituximab treatment, and infections. <br/>Findings from the studies included in this thesis highlight the important role of immune cells in the pathogenesis and clinical outcome of ANCA-associated vasculitis. However, a clear and comprehensive understanding of the immune cell alterations involved in AAV is still lacking, warranting further investigation.<br/>}},
author = {{Smargianaki, Sofia}},
isbn = {{978-91-8021-827-6}},
issn = {{1652-8220}},
keywords = {{ANCA associated vasculitis; GPA; MPA; B-cell; granulocytes; neutrophils; monocytes}},
language = {{eng}},
number = {{2026:29}},
publisher = {{Lund University, Faculty of Medicine}},
school = {{Lund University}},
series = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
title = {{Immune Cell Subsets in ANCA-Associated Vasculitis}},
url = {{https://lup.lub.lu.se/search/files/242835158/Avhandling_Sofia_Smargianaki_LUCRIS.pdf}},
year = {{2026}},
}