Correlation of disease activity with clonal expansions of human papillomavirus 16-specific CD8+ T-cells in patients with severe erosive oral lichen planus

Patent metadata

Field	Value
Publication number	US-10018629-B2
Application number	US-201414910612-A
Country	US
Kind code	B2
Filing date	Aug 8, 2014
Priority date	Aug 8, 2013
Publication date	Jul 10, 2018
Grant date	Jul 10, 2018

Abstract

A massive clonal expansion of activated CD8 + T-cells with increased frequency of HPV 16-specific CD8 + T-cells was discovered to be a characteristic of oral lichen planus (OLP), indicating a causal link between HPV infection and the dysimmune process. The invention relates to compositions and methods for the diagnosis and treatment of OLP patients.

First claim

We claim:

1. A method for detecting the presence of an immune response against a human papilloma virus infection in a blood sample of an oral lichen planus (OLP) patient, said method comprising:
isolating T cells from a blood sample from an OLP patient; and
detecting the presence of an immune response against a human papilloma virus infection in the blood sample by detecting CDR3β length distribution profiles of the TCRVβ3 gene segment in the CD8+ T cells expressing a TCRVβ3 specific for HPV16.

2. The method of claim 1 , further comprising treating the patient with an anti-HPV treatment or anti-HPV drug.

3. The method of claim 2 , wherein the anti-HPV treatment or anti-HPV drug is cidofovir.

4. The method of claim 1 , further comprising preparing nucleic acids from the blood sample and contacting the nucleic acids with an HPV specific primer or probe.

5. A method for detecting the presence of an immune response against a human papilloma virus infection in a blood sample of an oral lichen planus (OLP) patient, said method comprising:
isolating T cells from the blood sample; and
detecting expansion of a clonal population of CD8+TCRVβ3+ T cells recognizing the HPV16 E711-20 epitope in the sample,
wherein said clonal population has a single CDR3β sequence in the TCRVβ3 gene segment.

6. The method of claim 5 , wherein the CDR3β sequence in the TCRVβ3 gene segment in the CD8+ T cells of the cell sample encodes any one of SEQ ID NOs 1-10.

7. The method of claim 5 , further comprising treating the patient with an anti-HPV treatment or anti-HPV drug.

8. The method of claim 7 , wherein the anti-HPV treatment or anti-HPV drug is cidofovir.

9. The method of claim 5 , further comprising preparing nucleic acids from the cell sample and contacting the nucleic acids with an HPV specific primer or probe.

Assignees

• Pasteur Institut
• Inst Nat Sante Rech Med
• Univ Paris Diderot Paris 7
• Assist Publique—Hopitaux De Paris
• Pasteur Institut
• Univ Paris Diderot Paris 7

Inventors

• Gougeon Marie-Lise
• Viguier Manuelle
• Bachelez Hervé
• Fazilleau Nicolas

Classifications

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title

• A61K31/675

  having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate · CPC title

• G01N33/505

  involving T-cells · CPC title

• C12Q1/6869

  Methods for sequencing · CPC title

• C12Q1/04

  Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor {(C12Q1/6897 takes precedence)} · CPC title