Neutrophil directional chemotaxis in children with Papillon Lefévre Syndrome

Objectives: Aim: To functionally characterise neutrophil behaviour in PLS patients compared with healthy gender and age-matched controls.

Papillon-Lefevre Syndrome (PLS) is an extremely rare inherited autosomal recessive disease apparent in chldren aged between 1-4 years and a prevalence of 1-4 people per million. PLS is characterised by palmoplantar keratosis and severe periodontal destruction leading to premature and permanent loss of teeth, 20-25% of PLS cases suffer from an increased susceptibility to other infections.
PLS is caused by a mutation in the cathepsin C gene (CTSC), resulting in a complete loss of activity and subsequent failure to activate immune response proteins. The underlying cause of periodontal disease in PLS patients is thought to arise from a consequent defect in neutrophils, which are vital for defence against pathogens and in the progression of periodontal inflammation.
Methods: Neutrophils were isolated from the peripheral blood of 5 genotyped PLS patients alongside healthy age and gender–matched controls. Chemotaxis was analysed by real-time video-microscopy. Other neutrophil immune functions including Reactive Oxygen Species (ROS) generation and Neutrophil Extracellular Trap (NET) formation were also assayed using periodontally relevant bacteria/other stimuli..
Results: No significant differences were observed for neutrophil speed or velocity towards host and bacteria-derived chemoattractants, however PLS neutrophils exhibited reduced chemotactic accuracy. PLS neutrophils generated significantly more ROS and significantly lower NETs when stimulated.
Conclusions: These results enhance our understanding of the underlying neutrophil defect in PLS patients.