Oral Phenotype and Immunological Profile of Patients with Papillon-Lefèvre Disease

Objectives: The Papillon-Lefèvre disease (PLD) is an autosomal recessive syndrome related to mutations in the cathepsin-C gene. The objective of this study was to evaluate the oral phenotype and immunological profile of three sisters with PLD.
Methods: In accordance with Helsinki Declaration and after ethics committee approval, dental pulp and periodontal ligament were removed from extracted teeth from PLD patients (due to the disease) and third molars of healthy patients (control group, orthodontic purposes). RNA samples were extracted following the Trizol protocol. Thereafter, the cDNAs were synthetized and used as templates in real-time PCR (qPCR) of the genes: Tumor necrosis factor alpha (TNF-α), Interleukin-3 (IL-3) and reference gene (Glycerol-3-phosphate dehydrogenase, GAPDH). The experiments were repeated 3 times independently (n=3/group) and gene fold of expression was calculated by ΔΔct method. The phenotype was established in clinical exams and the immunoglobulins quantified in peripherical blood samples. Statistics: ANOVA, Bonferroni (p<0.05).
Results: The IL-3 and TNF-α genes were significantly overexpressed in samples of periodontal ligament and dental pulp of PLD patients, compared to the control group. The immunoglobulin test of PLD patients showed that both IgE and IgG were largely above the reference value. For PLD patients IgE is approximately 1343KU/L and ≤114KU/L reference value, respectively and for IgG it is approximately 2230mg/dL and 793mg/dL to 1390mg/dL reference value, respectively. The phenotype of these patients is keratoderma palmoplantar, early loss of deciduous and permanent dentition, loss of bone insertion, fast and aggressive bone loss, hemorrhagic gum and periodontitis.
Conclusions: The mutation of cathepsin-C seems to lead to an evident impairment of immunological profile in PLD and the IL-3 and TNF-α regulate part of the immune and inflammatory reactions. The PLD phenotype, the immunoglobulin’s data, and gene expression pattern resemble an autoimmune response.