B cell phenotype and function in granulomatosis with polyangiitis: Towards prediction of relapse

Judith Land

B cell phenotype and function in granulomatosis with polyangiitis: Towards prediction of relapse

Judith Land

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Samenvatting

Vasculitis is een verzamelnaam die gebruikt wordt voor ziektes waarbij de bloedvaatwanden ontstoken zijn. Binnen de vasculitis bestaat er een subgroep van ziektebeelden die gekenmerkt zijn door de aanwezigheid van autoantilichamen, anti-neutrofiele cytoplasma antilichaam (ANCA) geassocieerde vasculitis (AAV). Deze term omvat onder andere granulomatose met polyangiitis (GPA).

De meerderheid van GPA patiënten krijgt te maken met opvlammingen van ziekteactiviteit, een recidief genoemd. Elk recidief gaat gepaard met toenemende schade in de betrokken organen. Wanneer een recidief voorspeld zou kunnen worden, zouden patiënten tijdig behandeld kunnen worden om de opvlamming mogelijk te voorkomen.

Veel typen immuuncellen zijn betrokken bij de pathogenese van AAV, het onderzoek beschreven in dit proefschrift is gericht op B-cellen. Er werd gekeken naar het fenotype en de functie van B-cellen in gezonde controles en in GPA patiënten met en zonder recidief. Hierbij werd onder andere onderzoek gedaan naar productie van ANCA, productie van cytokines en de distributie van verschillende B-cel populaties.

Er waren verschillen zichtbaar tussen patiënten met en zonder een aankomend recidief. Zo nam in een deel van de patiënten de ANCA productie toe voor een recidief. Daarnaast weken patiënten voor een recidief meer af van gezonde controles wat betreft de B-cel subset distributie, met lage percentages geheugen en CD24highCD27+ B-cellen. Dit maakt het monitoren van de B-cel subset distributie mogelijk interessant voor het helpen voorspellen van recidieven. Tevens waren er verschillen in B-cel cytokine productie, waarbij GPA patiënten minder TNFα-producerende B-cellen hadden dan controles, en in individuele patiënten het percentage IL10-producerende B-cellen afnam voor een recidief.

Originele taal-2	English
Kwalificatie	Doctor of Philosophy
Toekennende instantie	Rijksuniversiteit Groningen
Begeleider(s)/adviseur	Heeringa, Peter, Supervisor Stegeman, Coen, Supervisor Rutgers, Bram, Co-supervisor Abdulahad, Wayel, Co-supervisor Bos, Nico, Beoordelingscommissie Navis, Gerjan, Beoordelingscommissie Little, M. A., Beoordelingscommissie, Externe Persoon
Datum van toekenning	13-jun.-2016
Plaats van publicatie	[Groningen]
Uitgever	Rijksuniversiteit Groningen
Gedrukte ISBN's	978-94-6182-683-1
Elektronische ISBN's	978-94-6182-687-9
Status	Published - 2016

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Title and contents Final publisher's version, 236 KB
Chapter 1 Final publisher's version, 1,27 MB
Chapter 2 Final publisher's version, 1,47 MB
Chapter 3 Final publisher's version, 1,98 MB
Chapter 4 Final publisher's version, 1,53 MB
Chapter 5 Final publisher's version, 735 KB
Chapter 6 Final publisher's version, 454 KB
Chapter 7 Final publisher's version, 721 KB
Chapter 8 Final publisher's version, 377 KB
Chapter 9 Final publisher's version, 81,8 KB
Dankwoord Final publisher's version, 41,9 KB
Curriculum VitaeFinal publisher's version, 24,8 KB
Complete thesisFinal publisher's version, 8,41 MB
PropositionsFinal publisher's version, 23,5 KB

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title = "B cell phenotype and function in granulomatosis with polyangiitis: Towards prediction of relapse",

abstract = "Vasculitis is a term used to indicate a spectrum of disorders that present with inflammation of the blood vessel walls. A subgroup of disorders is characterised by the presence of autoantibodies, the anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAV). AAV includes granulomatosis with polyangiitis (GPA).GPA patients have a high risk of disease relapse, up to 60% in 5 years. Each relapse affects the quality of life of the patient, and can lead to increased organ damage. When relapses could be predicted it could be possible to prevent relapses through timely intervention. Many types of immune cells are involved in GPA, in this thesis we focused on the B cells. The B cell phenotype and function was investigated in healthy controls and GPA patients with and without a relapse, including distribution of different B cell subsets, production of PR3-ANCA IgG and production of pro- and anti-inflammatory cytokines.Results included that several differences were found between patients with and without a relapse. In a number of patients, the in vitro production of ANCA increased prior to relapse. Furthermore, there were changes in the B cell subset distribution in GPA patients compared to controls, and these were most pronounced in patients prior to relapse. Before relapse low and decreasing percentages of memory and CD24highCD27+ B cells were seen. Indicating that monitoring the B cell subset distribution could potentially be interesting with regard to relapse prediction. There were also differences in cytokine production, as GPA patients had fewer TNFα producing B cells than controls, and it appeared that IL10 producing B cells may decrease in individual patients prior to relapse.",

author = "Judith Land",

year = "2016",

language = "English",

isbn = "978-94-6182-683-1",

publisher = "Rijksuniversiteit Groningen",

school = "University of Groningen",

}

TY - THES

T1 - B cell phenotype and function in granulomatosis with polyangiitis

T2 - Towards prediction of relapse

AU - Land, Judith

PY - 2016

Y1 - 2016

N2 - Vasculitis is a term used to indicate a spectrum of disorders that present with inflammation of the blood vessel walls. A subgroup of disorders is characterised by the presence of autoantibodies, the anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAV). AAV includes granulomatosis with polyangiitis (GPA).GPA patients have a high risk of disease relapse, up to 60% in 5 years. Each relapse affects the quality of life of the patient, and can lead to increased organ damage. When relapses could be predicted it could be possible to prevent relapses through timely intervention. Many types of immune cells are involved in GPA, in this thesis we focused on the B cells. The B cell phenotype and function was investigated in healthy controls and GPA patients with and without a relapse, including distribution of different B cell subsets, production of PR3-ANCA IgG and production of pro- and anti-inflammatory cytokines.Results included that several differences were found between patients with and without a relapse. In a number of patients, the in vitro production of ANCA increased prior to relapse. Furthermore, there were changes in the B cell subset distribution in GPA patients compared to controls, and these were most pronounced in patients prior to relapse. Before relapse low and decreasing percentages of memory and CD24highCD27+ B cells were seen. Indicating that monitoring the B cell subset distribution could potentially be interesting with regard to relapse prediction. There were also differences in cytokine production, as GPA patients had fewer TNFα producing B cells than controls, and it appeared that IL10 producing B cells may decrease in individual patients prior to relapse.

AB - Vasculitis is a term used to indicate a spectrum of disorders that present with inflammation of the blood vessel walls. A subgroup of disorders is characterised by the presence of autoantibodies, the anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAV). AAV includes granulomatosis with polyangiitis (GPA).GPA patients have a high risk of disease relapse, up to 60% in 5 years. Each relapse affects the quality of life of the patient, and can lead to increased organ damage. When relapses could be predicted it could be possible to prevent relapses through timely intervention. Many types of immune cells are involved in GPA, in this thesis we focused on the B cells. The B cell phenotype and function was investigated in healthy controls and GPA patients with and without a relapse, including distribution of different B cell subsets, production of PR3-ANCA IgG and production of pro- and anti-inflammatory cytokines.Results included that several differences were found between patients with and without a relapse. In a number of patients, the in vitro production of ANCA increased prior to relapse. Furthermore, there were changes in the B cell subset distribution in GPA patients compared to controls, and these were most pronounced in patients prior to relapse. Before relapse low and decreasing percentages of memory and CD24highCD27+ B cells were seen. Indicating that monitoring the B cell subset distribution could potentially be interesting with regard to relapse prediction. There were also differences in cytokine production, as GPA patients had fewer TNFα producing B cells than controls, and it appeared that IL10 producing B cells may decrease in individual patients prior to relapse.

M3 - Thesis fully internal (DIV)

SN - 978-94-6182-683-1

PB - Rijksuniversiteit Groningen

CY - [Groningen]

ER -