Papillon-LefÃ¨vre syndrome patient reveals species-dependent requirements for neutrophil defenses.

[papillon-lefÃ¨vre syndrome]

Papillon-LefÃ¨vre syndrome (PLS ) results from mutations that inactivate cysteine protease cathepsin C (CTSC ), which processes a variety of serine proteases considered essential for antimicrobial defense . Despite serine protease-deficient immune cell populations , PLS patients do not exhibit marked immunodeficiency . Here , we characterized a 24 -year -old woman who had suffered from severe juvenile periodontal disease , but was otherwise healthy , and identified a homozygous missense mutation in CTSC indicative of PLS . Proteome analysis of patient neutrophil granules revealed that several proteins that normally localize to azurophil granules , including the major serine proteases , elastase , cathepsin G , and proteinase 3 , were absent . Accordingly , neutrophils from this patient were incapable of producing neutrophil extracellular traps (NETs ) in response to ROS and were unable to process endogenous cathelicidin hCAP-18 into the antibacterial peptide LL-37 in response to ionomycin . In immature myeloid cells from patient bone marrow , biosynthesis of CTSC and neutrophil serine proteases appeared normal along with initial processing and sorting to cellular storage . In contrast , these proteins were completely absent in mature neutrophils , indicating that CTSC mutation promotes protease degradation in more mature hematopoietic subsets , but does not affect protease production in progenitor cells . Together , these data indicate CTSC protects serine proteases from degradation in mature immune cells and suggest that neutrophil serine proteases are dispensable for human immunoprotection .

Diseases
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Diseases presenting "biosynthesis of ctsc and neutrophil serine proteases appeared normal along with initial processing and sorting to cellular storage" symptom

papillon-lefÃ¨vre syndrome

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