Implication of Human Papillomavirus (HPV) in Lichen Physiopathology in Human (HPVLichen) (HPVLichen)

Implication of Human Papillomavirus (HPV) in Lichen Physiopathology in Human

Lichen planus is a chronic cutaneous and mucosal disease characterized by the infiltration of cluster of differentiation (CD) CD8 T lymphocytes, localized under the basal membrane and associated with apoptosis of basal keratinocytes, suggesting a reactivity of T lymphocytes toward keratinocyte antigen(s), so far unidentified. In a recent study, the research team at Institut Pasteur has demonstrated in a peculiar clinical form of lichen planus (erosive lichen planus), that the immunogenic target of CD8 T lymphocytes could be the immunodominant peptide of Human Papilloma Virus (HPV) 16.

In line with this recent work which shows for the first time a link between HPV-16 and an autoimmune disease, erosive lichen planus, the aim of te study is to test the hypothesis that HPV could be also involved in the pathogenesis of other clinical forms of lichen, such as non erosive lichen planus or lichen sclerosus.

Study Overview

• Status: Completed
• Conditions: Lichen Planus
• Intervention / Treatment: Procedure: Human biological samples

Detailed Description

Lichen planus is a chronic cutaneous and mucosal disease characterized by the infiltration of cluster of differentiation (CD) CD8 T lymphocytes, localized under the basal membrane and associated with apoptosis of basal keratinocytes, suggesting a reactivity of T lymphocytes toward keratinocyte antigen(s), so far unidentified. In a recent study, the research team at Institut Pasteur has demonstrated in a peculiar clinical form of lichen planus (erosive lichen planus), that the immunogenic target of CD8 T lymphocytes could be the immunodominant peptide of Human Papilloma Virus (HPV) 16.

In line with this recent work which shows for the first time a link between HPV-16 and an autoimmune disease, erosive lichen planus, the aim of te study is to to test the hypothesis that HPV could be also involved in the pathogenesis of other clinical forms of lichen, such as non erosive lichen planus or lichen sclerosus.

Regarding erosive lichen planus, the aim is to test the cytotoxic function of the previously identified CD8 T lymphocytes specific for HPV16 E711-20.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Besançon, France
    • Service de Dermatologie du CHU de Besançon
  • Paris, France
    • Service de Dermatologie de l'hôpital Saint Louis
  • Reims, France
    • Service de Dermatologie du CHU de Reims

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• At least 18 year-old
• Clinically or histologically confirmed lichen : Non-erosive lichen planus, Erosive lichen planus, or Sclerosus lichen
• At diagnosis of desease before treatment, or during flares of the disease, with or without intake or topical application of immunosuppressants
• Affiliated or beneficiary of a social security system
• Informed and written consent

Exclusion Criteria:

• Under 18 year-old,
• Legal protection measures,
• Inability to consent
• Pregnant or breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with lichen; Patients with non-erosive lichen planus, erosive lichen planus or lichen sclerosus. Human biological samples : Blood sample; Skin or mucosal brushing; Skin or mucosal biopsy	Procedure: Human biological samples; Blood sample; Skin or mucosal brushing; Skin or mucosal biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The use of the different segments of the Vbeta gene assessed by quantitative PCR, and the distribution of the different sizes of the complementarity determining regions (CDR) CDR3 by immunoscope.	In patients with a non-erosive type of lichen and with a lichen sclerosus et atrophicus, the hypothesis for oligoclonal bias in the T-cell receptor repertoire on peripheral and in situ CD4 and CD8 T lymphocytes will be tested realizing, on the 2 sorted subpopulations, a study of the use of the different segments of the Vbeta gene using quantitative Polymerase Chain Reaction (PCR) and a study of the distribution study of the different sizes of the CDR3 using immunoscope method. Depending on whether or not bias in the T-cell receptor repertoire exists, the study will be continued by looking for the same repertoire bias in situ, on injury site (skin or mucous, depending on the clinical type of lichen), and the research of clonal sequences (or clonotypes) from RNA of patients after cloning and complete sequencing. If clonotype T CD8 Vbeta3 are identified in these types of lichen, their specificity to HPV16 E711-20 wil be assessed by flow cytometry.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The functionality and the cytotoxicity of CD8 Vbeta3 peripheric T lymphocytes assessed by flow cytometry.	In patients with erosive lichen planus, the functionality and the cytotoxicity of CD8 Vbeta3 peripheric T lymphocytes will be assessed showing their ability to recognize and destroy a target carrier of HPV16 E711-20 peptide by flow cytometry.	2 years

Collaborators and Investigators

• Sponsor: Institut Pasteur
• Collaborators: Société de Dermatologie Française
• Investigators: Study Director: Marie-Lise Gougeon, Institut Pasteur

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2016
• Primary Completion (Actual): April 16, 2018
• Study Completion (Actual): April 16, 2018

Study Registration Dates

• First Submitted: April 22, 2016
• First Submitted That Met QC Criteria: May 2, 2016
• First Posted (Estimate): May 4, 2016

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: February 14, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Lichenoid Eruptions; Lichen Planus
• Other Study ID Numbers: 2015-058; ID-RCB number : 2015-A01697-42 (Other Identifier: French national registration number of the study)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No