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

Institut Pasteur21 enrolled

Overview

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.

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

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: 2 years

Secondary Outcomes

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.