The triangular relationship between Sjögren syndrome, autophagy and HMGB1.

Boer, M. (Myrte) (2014) The triangular relationship between Sjögren syndrome, autophagy and HMGB1. thesis, Medicine.

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Abstract

Introduction: Sjögren syndrome is an auto-immune disease in which the lacrimal and salivary glands are affected. SjS is not curable partly because the limited knowledge about the pathogenesis of the disease. Previous study showed that autophagy might play a role in the pathogenesis of SjS. Autophagy is important for cell survival whereby the cell self-digests its own cell components. Autophagy is important in the elimination and thus prevention of accumulation of proteins, organelles and reactive oxygen species (ROS). Reduced autophagy leads to increased accumulation ROS resulting in apoptosis and necrosis. Necrosis results in the release of DAMPs. HMGB1 is one of the best described DAMPs. Materials and methods: In this study serum HMGB1 and anti-HMGB1 levels in 30 SjS patients and 30 healthy controls are measured by resp. western blot and ELISA. Further, from 28 SjS patients, who received Rituximab, the (anti-)HMGB1 levels are measured before and 16 and 24 weeks after treatment. To develop a cell model to study autophagy in vitro, A253 epithelial cells are starved with HBSS to induce autophagy. Autophagy related genes ATG5, ATG7 and HMGB1 expression are measured after 1,2 and 6 hours of starvation. Results: serum analysis showed increased (IgG anti-)HMGB1 levels before Rituximab treatment. Before treatment HMGB1 correlates with ESSDAI. After treatment there is no correlation. Anti-HMGB1 correlates only with the ESSDAI score 24 weeks after treatment. Stimulation of the A253 cells resulted in increased ATG5 and ATG7 expression. Conclusion: HMGB1 and IgG anti-HMGB1 are both increased in SjS patients and decreased after Rituximab treatment. This suggest a role of (anti-)HMGB1 in the pathogenesis of SjS. Whether autophagy is important in this increased release of HMGB1 and in the pathogenesis of SjS needs further study. The A253 cell model needs further optimization to study autophagy in vitro.

Item Type:	Thesis (Thesis)
Supervisor name:	Kroese, Prof. dr. F.G.M. and Bouma, dr. H.R. and Rheumatology and Clinical Immunology and UMCG
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:56
Last Modified:	25 Jun 2020 10:56
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1628

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