Low Density Granulocytes (LDG) in the pathogenesis of Systemic Lupus Erythematosus (SLE): Targets for therapy?

Schultinga, Alice (2019) Low Density Granulocytes (LDG) in the pathogenesis of Systemic Lupus Erythematosus (SLE): Targets for therapy? Bachelor's Thesis, Biology.

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Abstract

Recently, it has become more apparent that Low Density Granulocytes (LDG) are a subgroup of neutrophils with possible involvement in different auto-immune diseases. LDGs have increased Neutrophil Extracellular Trap (NET) formation activity, increased type I Interferon (IFN) production, lower apoptosis rates and, pro-inflammatory effects. LDGs possess cell-surface molecules which are characteristic for an activated phenotype, yet the morphological appearance of their nuclei is more like that of an immature neutrophil. This difference supports the contention of LDGs being a subgroup of neutrophils. The increased pro-inflammatory activity of LDGs may have detrimental effects on the development and progression of Systemic Lupus Erythematosus (SLE). SLE is an auto-immune disease characterised by chronic, widespread inflammation. This inflammation and autoimmunity affects multiple organs and have different manifestations such as glomerulonephritis, atherosclerosis and skin rash. Recent studies have shown that patients with SLE have a higher cell-count of LDGs compared to healthy patients and that a higher LDGs cell-count correlated with more double-stranded-DNA antibodies. These antibodies are known to be present in SLE patients. This together promotes the thought of LDGs being a key-player in the development and progression of SLE. Considering the current therapeutic approach, namely alleviating symptoms of the disease, more specific therapeutic targets are needed in order to minimize the side-effects and to preserve the defensive capabilities of the immune system. The purpose of this thesis is to obtain more insights in the activity of LDGs in SLE and to provide possible therapeutic targets for LDGs to improve the treatment of patients with SLE. Intervention in the activity of LDGs seems promising and could provide therapeutic possibilities in the future. Since LDGs have a pro-inflammatory phenotype, production of factors such as type I IFNs are increased. Literature has shown that inhibition of type I IFNs reduces SLE activity, which suggests inhibiting LDG may indirectly reduce type I IFNs as well. Furthermore, inhibition of NET formation also reduced manifestations of SLE such as glomerulonephritis. Additionally, neutrophils are thought to be involved in the pathogenesis of SLE as well, since depletion of neutrophils showed a reduced SLE phenotype. For this reason, depletion of LDGs may reduce SLE activity to a greater extent since these cells have an increased pro-inflammatory phenotype compared to normal neutrophils. However, current literature still remains controversial on the effect of inhibition of LDGs activity, implying the value of more knowledge on this topic.

Item Type:	Thesis (Bachelor's Thesis)
Supervisor name:	Heeringa, P.
Degree programme:	Biology
Thesis type:	Bachelor's Thesis
Language:	English
Date Deposited:	08 Jul 2019
Last Modified:	10 Jul 2019 14:42
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/20008

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