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Title: The role of properdin in the pathogenesis of murine systemic lupus erythematosus
Author: Al Aridhee, Hasanain Y. M.
ISNI:       0000 0004 8498 2506
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2019
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In systemic lupus erythematosus (SLE), complement-activating immune complexes (ICs) are central to the immunopathogenesis of disease. Their deposition in kidney initiates an inflammatory response resulting in glomerulonephritis. Properdin is the only known positive regulator of complement activation, but its role in SLE disease severity has not been studied yet. Properdin-deficient mice were crossed with MRL/lpr mice on C57Bl/6 background. MRL/lpr mice develop lupus-like disease spontaneously. We derived properdin wildtype, properdin deficient, and properdin heterozygous MRL/lpr mice. Compared to MRL/lpr properdin wildtype mice, MRL/lpr properdin-deficient mice developed significantly less severe disease, had lower serum anti-DNA antibody titre, reduced complement activation, less serum pro-inflammatory cytokines and showed less splenic surface expression of CR2 on B220 positive cells. Parallel analysis of properdin heterozygous MRL/lpr mice revealed a gene dose effect in some measures. There was less serum creatinine in MRL/lpr properdin-deficient mice and colocalising activated C3 fragments and immunoglobulins (ICs) in the mesangium, and less SMA-α and nephrin expression in MRL/lpr properdin-deficient mice compared to MRL/lpr properdin wildtype mice. These findings demonstrate that properdin plays a significant role in the severity of lupus and involvement of kidney in MRL/lpr mice. Because MRL/lpr properdin deficient mice had lower levels of anti-DNA Abs, inflammatory mediators and marker of renal impairment, the study implies that properdin could constitute a novel therapy target.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Thesis