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

Copy link to clipboard


  • Title and contents

    Final publisher's version, 63 KB, PDF document

  • Chapter 1

    Final publisher's version, 2 MB, PDF document

  • Chapter 2

    Final publisher's version, 454 KB, PDF document

  • Chapter 3A

    Final publisher's version, 535 KB, PDF document

  • Chapter 3B

    Final publisher's version, 334 KB, PDF document

  • Chapter 4

    Final publisher's version, 1 MB, PDF document

  • Chapter 5

    Final publisher's version, 406 KB, PDF document

  • Chapter 6

    Final publisher's version, 1 MB, PDF document

  • Chapter 7

    Final publisher's version, 2 MB, PDF document

  • Chapter 8

    Final publisher's version, 2 MB, PDF document

  • Chapter 9

    Final publisher's version, 1 MB, PDF document

  • Chapter 10

    Final publisher's version, 838 KB, PDF document

  • Chapter 11

    Final publisher's version, 109 KB, PDF document

  • Complete thesis

    Final publisher's version, 12 MB, PDF document

  • Propositions

    Final publisher's version, 261 KB, PDF document

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
Award date2-Jul-2018
Place of Publication[Groningen]
Print ISBNs978-94-034-0722-7
Electronic ISBNs978-94-034-0721-0
Publication statusPublished - 2018

Download statistics

No data available

ID: 61753719