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T cell-dependent B cell hyperactivity in primary Sjögren's syndrome: Biomarker and target for treatment

Verstappen, G., 2018, [Groningen]: University of Groningen. 248 p.

Research output: ThesisThesis fully internal (DIV)Academic

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  • Title and contents

    Final publisher's version, 63 KB, PDF document

  • Chapter 1

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  • Chapter 2

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  • Chapter 3A

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  • Chapter 3B

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  • Chapter 4

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  • Chapter 5

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  • Chapter 6

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  • Chapter 7

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  • Chapter 8

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  • Chapter 9

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  • Chapter 10

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  • Chapter 11

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  • Complete thesis

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  • Propositions

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Primary Sjögren’s syndrome (pSS) is a chronic, systemic autoimmune disease, which predominantly affects the salivary and lacrimal glands. The main symptoms of pSS are a sensation of dry mouth, dry eyes, and chronic fatigue. In addition to the salivary and lacrimal glands, many other organs can be affected by the disease as well. pSS is characterized by over-activity of the adaptive immune system, in particular by hyperactivity of B lymphocytes (B cells). The aim of this thesis was to assess the role of T cell-dependent B cell hyperactivity as biomarker and target for treatment in pSS. We found that the frequency of T follicular helper (Tfh) cells in blood is a useful biomarker of systemic disease activity in pSS. However, locally in the inflamed glandular tissue also other T cell subsets and epithelium-associated B cells contribute significantly to the disease. Additionally, we reported in this thesis that the ratio of serum immunoglobulin free light chains (κ/λ) is a feasible biomarker of MALT-lymphoma presence in the salivary glands. In the second part of this thesis we studied the effects of treatment with rituximab or abatacept on T cell-dependent B cell hyperactivity in pSS patients. In particular Tfh cells in blood were affected by treatment, and their reduction correlated with decreased disease activity. Furthermore, abatacept treatment (which is aimed at T cell inhibition) also reduced B cell activity. We concluded that inhibition of the interaction between Tfh cells and B cells is crucial for successful treatment of disease activity in pSS.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
Award date2-Jul-2018
Place of Publication[Groningen]
Publisher
Print ISBNs978-94-034-0722-7
Electronic ISBNs978-94-034-0721-0
Publication statusPublished - 2018

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