Evaluation of Proteinase 3 Expression on Membrane of Papillon-Lefèvre Syndrome Neutrophils

Background: Proteinase 3, in its membrane form, is the main target antigen of anti-neutrophil autoantibodies in granulomatosis with polyangiitis (autoimmune disease). This neutrophil serine protease is synthesized as inactive zymogens at the early stage of neutrophil maturation and is activated by cathepsin C, the physiological activator of serine proteases. In neutrophils of Papillon-Lefevre syndrome patients, a genetic form of cathepsin C deficiency, amounts of intracellular proteinase 3 detected are very low or even undetectable. The aim of our study was to evaluate membrane expression of proteinase 3 on cathepsin C-deficient neutrophils by using the Papillon-Lefevre syndrome model in view of a therapeutic approach of granulomatosis with polyangiitis. Methods: We evaluated membrane expression of proteinase 3 on activated neutrophils of Papillon-Lefevre syndrome patients by cytometry. Results: Proteinase 3 was detected at neutrophils surface of Papillon-Lefevre syndrome patients, but significantly less than at healthy neutrophils surface. Conclusion: Pharmacological inhibition of cathepsin C may be an attractive therapeutic approach to eliminate the target autoantigen proteinase 3 of granulomatosis with polyangiitis patients.