ArticleThe Journal of clinical investigation2014
Papillon-Lefèvre syndrome patient reveals species-dependent requirements for neutrophil defenses.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 164 citations in OpenAlex.
- Cathepsin C (dipeptidyl peptidase 1) inhibition in adults with bronchiectasis: AIRLEAF, a phase II randomised, double-blind, placebo-controlled, dose-finding study.The European respiratory journal · 2025Trial
- Periodontal Effects of the Reversible Dipeptidyl Peptidase 1 Inhibitor Brensocatib in Bronchiectasis.JDR clinical and translational research · 2024Trial
- Dipeptidyl peptidase-1 inhibition with brensocatib reduces the activity of all major neutrophil serine proteases in patients with bronchiectasis: results from the WILLOW trial.Respiratory research · 2023Trial
- Dipeptidyl Peptidase 1 Inhibitor AZD7986 Induces a Sustained, Exposure-Dependent Reduction in Neutrophil Elastase Activity in Healthy Subjects.Clinical pharmacology and therapeutics · 2018Trial
- Differential antibacterial control by neutrophil subsets.Blood advances · 2018Trial
- Epithelial desquamation observed in a phase I study of an oral cathepsin C inhibitor (GSK2793660).British journal of clinical pharmacology · 2017Trial
- The dipeptidyl peptidase 1 inhibition landscape in bronchiectasis and its future direction.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Long-term periodontal maintenance in a patient with Papillon-Lefèvre syndrome: an 8-year case report.BMC oral health · 2026Article
- Cathepsin C orchestrates RSV-induced asthma exacerbation through the dual effect of monocyte-derived macrophages.Cellular & molecular immunology · 2026Article
- Immunology of Sepsis.Clinics in chest medicine · 2026Review
- Impact of dipeptidyl peptidase I and neutrophil serine proteases on neutrophil functional responses.Frontiers in pharmacology · 2026Article
- Differences in Inflammatory Genetic Profiles in Periodontitis Associated with Genetic and Immunological Disorders: A Systematic Review.Biomedicines · 2025Review
- It's a Trap!-Potential of Cathepsins in NET Formation.International journal of molecular sciences · 2025Review
- Neutrophil-derived biomarkers in bronchiectasis: identifying a common therapeutic target.The European respiratory journal · 2025Review
- Neutrophils and NETs in kidney disease.Nature reviews. Nephrology · 2025Review
- Dipeptidyl peptidase-1 inhibitors in bronchiectasis.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Neutrophilic inflammation in bronchiectasis.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Genetic risk variants implicate impaired maintenance and repair of periodontal tissues as causal for periodontitis-A synthesis of recent findings.Periodontology 2000 · 2025Review
- Targeting neutrophil serine proteases in bronchiectasis.The European respiratory journal · 2025Review
- Cathepsin C inhibition reduces neutrophil serine protease activity and improves activated neutrophil-mediated disorders.Nature communications · 2024Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Papillon-Lefèvre 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.
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