- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01116934
Cytokines in Papillon-Lefèvre Syndrome
Observational Study on Cytokine Production by Leukocytes of Papillon-Lefèvre Syndrome Patients and Healthy Probands in Whole Blood Cultures
Study Overview
Status
Conditions
Detailed Description
MATERIAL AND METHODS Materials Lipopolysaccharide (LPS; Escherichia coli, serotype R515) was purchased from Alexis (Lausen, Switzerland) and adenosine triphosphate (ATP) from Sigma (Deisenhofen, Germany). Tumor necrosis factor α (TNF-α) was kindly provided by the Knoll AG (Ludwigshafen, Germany). IL-1β was from Invitrogen/Biosource (Karlsruhe, Germany).
Patients and healthy donors Five patients with established diagnose of PLS are under periodontal treatment at the Department of Periodontology, Center for Dental, Oral, and Maxillofacial Medicine (Carolinum) of the Johann Wolfgang Goethe-University Frankfurt am Main. Antiinfective therapy with adjunctive antibiotics has been rendered to all of them and they are under regular and frequent supportive therapy. The Department of Periodontology has contact to additional 5 PLS patients that are edentulous or under periodontal therapy elsewhere. All patients underwent complete oral examinations as well as inspection of the skin of the palms and soles. Each adult patient or parents received clinical and genetic counselling, and signed a consent form, approved by the ethic committees of the Universities of Dresden and Frankfurt/Main. Clinical data and mutations of all patients have been reported before. All these patients were invited to take part in this study. Healthy donors had abstained from taking drugs for two weeks prior to the study. Due to wide spread use of oral contraceptives only male probands were chosen. The study complied with the rules of the Declaration of Helsinki and was approved by the Institutional Review Board for Human Studies of the Medical Faculty of the Johann Wolfgang Goethe-University Frankfurt/Main (Application# 31/05). All participating individuals were informed on risks and benefit as well as the procedures of the study and gave written informed consent.
Whole blood culture Heparinized blood was mixed with an equal volume of culture medium (RPMI 1640 supplemented with 25 mM HEPES (2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid), 100 U/ml penicillin, 100 µg/ml streptomycin) and 1 ml aliquots were transferred into loosely sealed round-bottom polypropylene tubes (Greiner, Germany). Whole blood cultures were kept at 37 oC and 5 % CO2 for the indicated time periods. Thereafter, cell-free plasma/RPMI samples were obtained by centrifugation and stored at -70oC until assessment of cytokine concentrations by enzyme linked immunosorbent essay (ELISA). Experiments were started within 60 min of blood withdrawal. Thus, the whole blood cultures consisted of the whole range of white blood cells as well as erythrocytes. Except for determination of IL-1β release, cultures were either kept as unstimulated control or stimulated with LPS (10 or 100 ng/ml), or with the combination of IL-1β plus TNF-α (50 ng/ml each) for 24h. For determination of IL-1β release, cells were kept as unstimulated control or were stimulated with Toll-like receptor 4 ligand LPS (100 ng/ml) for altogether 5h. For efficient release of IL-1β from activated cultures, LPS was combined with ATP (2 mM) which was added during the last 2h of the 5h stimulation period in order to achieve activation of the purinoreceptor P2X7.
Analysis of cytokine release by ELISA analysis Concentrations of IL-8, IL-6, interferon-inducible protein (IP)-10, interferon (IFN) gamma (Pharmingen/BD Biosciences), and IL-1β, (R&D Systems), in plasma/RPMI samples were determined by ELISA according to the manufacturers' instructions.
Statistics The individual patient or proband was defined as statistical unit. Data are shown as median with interquartile range and are presented as pg/ml (IL-1β, IL-6, IP-10) or as ng/ml (IL-8). Medians were compared between PLS patients and healthy volunteers using the non parametric Mann Whitney U test. Statistical analysis was performed using a computer program (Systat for Windows version 10.0, Systat Inc., Evanston, IL, USA).
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Frankfurt/Main, Germany, 60596
- Department of Periodontology, Center for Dental, Oral, and Maxillofacial Medicine (Carolinum), JWG-University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Diagnose of PLS
Exclusion Criteria:
- No written informed consent
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
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PLS patients
Eight PLS patients (one female) from 6 families.
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Healthy controls
Healthy donors had abstained from taking drugs for two weeks prior to the study.
Due to wide spread use of oral contraceptives only male probands were chosen.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Serum Concentrations of Interleukin (IL)-1 Beta
Time Frame: 2006
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Concentrations of IL-8, IL-6, IP-10, interferon (IFN)-gamma, and IL-1 beta, in plasma/RPMI samples were determined by enzyme linked immunosorbent assay (ELISA) according to the manufacturers' instructions
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2006
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Peter Eickholz, Prof. Dr., JWG-University
Publications and helpful links
General Publications
- Eickholz P, Kugel B, Pohl S, Naher H, Staehle HJ. Combined mechanical and antibiotic periodontal therapy in a case of Papillon-Lefevre syndrome. J Periodontol. 2001 Apr;72(4):542-9. doi: 10.1902/jop.2001.72.4.542.
- Noack B, Gorgens H, Hoffmann T, Fanghanel J, Kocher T, Eickholz P, Schackert HK. Novel mutations in the cathepsin C gene in patients with pre-pubertal aggressive periodontitis and Papillon-Lefevre syndrome. J Dent Res. 2004 May;83(5):368-70. doi: 10.1177/154405910408300503.
- Lux CJ, Kugel B, Komposch G, Pohl S, Eickholz P. Orthodontic treatment in a patient with Papillon-Lefevre syndrome. J Periodontol. 2005 Apr;76(4):642-50. doi: 10.1902/jop.2005.76.4.642.
- Schacher B, Baron F, Ludwig B, Valesky E, Noack B, Eickholz P. Periodontal therapy in siblings with Papillon-Lefevre syndrome and tinea capitis: a report of two cases. J Clin Periodontol. 2006 Nov;33(11):829-36. doi: 10.1111/j.1600-051X.2006.00992.x. Epub 2006 Sep 13.
- Noack B, Gorgens H, Schacher B, Puklo M, Eickholz P, Hoffmann T, Schackert HK. Functional Cathepsin C mutations cause different Papillon-Lefevre syndrome phenotypes. J Clin Periodontol. 2008 Apr;35(4):311-6. doi: 10.1111/j.1600-051X.2008.01201.x. Epub 2008 Feb 20.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PLS-Cytokines
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