Analysis of urinary cathepsin C for diagnosing Papillon-Lefevre syndrome

Yveline Hamon (1, 2, 3, 4) , Monika Legowska (5) , Patricia Fergelot (6, 7, 8, 9) , Sandrine Dallet-Choisy (2, 3) , Louise Newell (10) , Lise Vanderlynden (2, 3) , Ali Kord Valeshabad (11) , Karina Acrich (12) , Hadi Kord (13) , Tsamakis Charalampos (10) , Fanny Morice-Picard (14, 7, 15) , Ian Surplice (10) , Jerome Zoidakis (16) , Karen David (12) , Antonia Vlahou (16) , Shivanna Ragunatha (17) , Nikoletta Nagy (18, 19, 20) , Katalin Farkas (18, 19, 20) , Marta Szell (18, 19, 20) , Cyril Goizet (6, 7, 8) , Beate Schacher (21) , Maurizio Battino (22, 23) , Abdullah Al Farraj Aldosari (24) , Xinwen Wang (25) , Yang Liu (26) , Sylvain Marchand-Adam (2, 3) , Adam Lesner (5) , Elodie Kara (27) , Sevil Korkmaz-Icoez (28) , Celia Moss (10, 29) , Peter Eickholz (21) , Alain Taieb (30, 7) , Salih Kavukcu (31) , Dieter E. Jenne (1, 4) , Francis Gauthier (2) , Brice Korkmaz (2)

1 Comprehensive Pneumology Center - Institute of Lung Biology and Disease (iLBD)
2 Université Francois Rabelais [Tours]
3 CEPR - Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100
4 MPIN - Max Planck Institute of Neurobiology
5 Faculty of Chemistry
6 U1211 Laboratoire Maladies Rares: Génétique et Métabolisme
7 UB - Université de Bordeaux
8 Hôpital Pellegrin - Service de Génétique Médicale
9 Centre de Référence des Anomalies du Développement Embryonnaire
10 Birmingham Children’s Hospital
11 Department of Physics [Boulder]
12 Medical Genetics Clinic
13 Bone Joint and Connective Tissue Disease Research Center (BJCRC), Department of Rheumatology, Faculty of Medicine
14 U1035 Centre de Référence pour les Maladies Rares de la Peau, Service de Dermatologie Adulte et Pédiatrique
15 CHU Bordeaux
16 Biotechnology Division - Biomedical Research Foundation
17 Department of Dermatology, Venereology, and Leprosy
18 Department of Medical Genetics
19 Department of Dermatology and Allergology [Szeged]
20 MTA-SZTE Dermatological Research Group
21 CHU Pitié-Salpêtrière [AP-HP]
22 Centre for Nutrition & Health
23 Department of Clinical Sciences
24 Department of Prosthetic, College of Dentistry
25 Department of Oral Medicine and Periodontology, School of Stomatology
26 Department of Periodontology
27 ReproPharm
28 Department of Cardiac Surgery
29 University of Birmingham
30 U1035 Centre de R ef erence pour les Maladies Rares de la Peau, Service de Dermatologie Adulte et Pédiatrique
31 Division of Pediatric Nephrology, Department of Pediatrics, School of Medicine

Papillon-Lefevre syndrome (PLS) (OMIM: 245000) is a rare disease characterized by severe periodontitis and palmoplantar keratoderma. It is caused by mutations in both alleles of the cathepsin C (CatC) gene CTSC that completely abrogate the proteolytic activity of this cysteine proteinase. Most often, a genetic analysis to enable early and rapid diagnosis of PLS is unaffordable or unavailable. In this study, we tested the hypothesis that active CatC is constitutively excreted and can be easily traced in the urine of normal subjects. If this is true, determining its absence in the urine of patients would be an early, simple, reliable, low-cost and easy diagnostic technique. All 75 urine samples from healthy control subjects (aged 3 months to 80 years) contained proteolytically active CatC and its proform, as revealed by kinetic analysis and immunochemical detection. Of the urine samples of 31 patients with a PLS phenotype, 29 contained neither proteolytically active CatC nor the CatC antigen, so that the PLS diagnosis was confirmed. CatC was detected in the urine of the other two patients, and genetic analysis revealed no loss-of-function mutation in CTSC, indicating that they suffer from a PLS-like condition but not from PLS. Screening for the absence of urinary CatC activity soon after birth and early treatment before the onset of PLS manifestations will help to prevent aggressive periodontitis and loss of many teeth, and should considerably improve the quality of life of PLS patients.

Mots clés: cathepsin C; diagnostic method; Papillon-Lefevre syndrome; protease; urine analysis

Domaines: Sciences du Vivant [q-bio]

Yveline Hamon, Monika Legowska, Patricia Fergelot, Sandrine Dallet-Choisy, Louise Newell, et al.. Analysis of urinary cathepsin C for diagnosing Papillon-Lefevre syndrome. FEBS Journal, 2016, 283 (3), pp.498 - 509. ⟨10.1111/febs.13605⟩. ⟨hal-01601404⟩