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Faculty of Medical Sciences

Histopathological assessment of germinal centers of patients with primary Sjögren’s syndrome Supervisor:

Nakshbandi, U. (Uzma) (2018) Histopathological assessment of germinal centers of patients with primary Sjögren’s syndrome Supervisor:. thesis, Medicine.

Full text available on request.

Abstract

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease which is characterized by the chronic inflammation of salivary and lacrimal glands leading to xerostomia and keratoconjunctivitis sicca. Although the immunopathogenesis of pSS is partly understood, B cell hyperactivity seems to be related to disease process, which is reflected by the presence of germinal centers (GCs). Primary SS patients who exhibit GCs within salivary gland parenchyma have higher focus scores and present with more disease activity than GC- pSS patients. Moreover, presence of GCs might be of clinical importance for stratification of RTX treatment. However there is considerable heterogeneity in reported findings concerning the presence of GCs. This can partially be explained by the difficulty in identifying GCs in diagnostic H&E sections and the lack of uniform histopathological criteria. This study was performed to assess the most appropriate way to identify GCs in salivary gland biopsies of pSS patients. In addition the level of lymphoid organization was determined in 42 pSS and 58 non-SS sicca patients. All parotid and labial salivary gland sections were stained with H&E as well as for CD3, CD20, CD21L, CD45, Ki67 and Bcl6. Presence of GCs, the number of GCs/mm2 salivary gland parenchyma and level of lymphoid organization were determined in all sections. We found that use of diagnostic H&E leads to an underestimation and incorrect identification of GCs, while using anti-CD21L overestimates GC counts. Furthermore, since Ki67 is an excellent marker for solely the dark zone of GCs, small GCs can be overlooked while other proliferative areas might be mistakenly identified as GCs. In addition we found that the majority of pSS- sicca patients were in stage 0 and 1, depending on their FS while roughly half of pSS patients were classified as stage 2 or 3 indicating progressive lymphoid organization. This study shows that staining for Bcl6 allows easy and unequivocal identification of GCs and should therefore be implemented in the histopathological evaluation of salivary gland biopsies of pSS patients.

Item Type: Thesis (Thesis)
Supervisor name: Supervisor: and Kroese, Prof. Dr. F. G. M. and Department of Rheumatology and Clinical Immunology and Second supervisor: and Vegt, Dr. B van der and Department of Pathology and Medical Biology and University Medical Center Groningen (UMCG)
Faculty: Medical Sciences
Date Deposited: 25 Jun 2020 10:48
Last Modified: 26 Apr 2021 12:16
URI: https://umcg.studenttheses.ub.rug.nl/id/eprint/896

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