WO2024104551A1 - Utilisation de la population de lymphocytes t cd4+ à mémoire effectrice slamf4+ ccr5+ en tant que biomarqueur dans la polyarthrite rhumatoïde - Google Patents

Utilisation de la population de lymphocytes t cd4+ à mémoire effectrice slamf4+ ccr5+ en tant que biomarqueur dans la polyarthrite rhumatoïde Download PDF

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WO2024104551A1
WO2024104551A1 PCT/EP2022/081802 EP2022081802W WO2024104551A1 WO 2024104551 A1 WO2024104551 A1 WO 2024104551A1 EP 2022081802 W EP2022081802 W EP 2022081802W WO 2024104551 A1 WO2024104551 A1 WO 2024104551A1
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cells
slamf4
ccr5
effector memory
tconv
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PCT/EP2022/081802
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Jérôme BITON
Natacha Bessis
Marie-Christophe Boissier
Mégane LACAUD
Houda Ghozlane BOUZIDI
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INSERM (Institut National de la Santé et de la Recherche Médicale)
Université Paris Xiii Paris-Nord
Assistance Publique - Hôpitaux De Paris (Aphp)
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Priority to PCT/EP2022/081802 priority Critical patent/WO2024104551A1/fr
Publication of WO2024104551A1 publication Critical patent/WO2024104551A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56966—Animal cells
    • G01N33/56972—White blood cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/52—Assays involving cytokines
    • G01N2333/521—Chemokines
    • G01N2333/523—Beta-chemokines, e.g. RANTES, I-309/TCA-3, MIP-1alpha, MIP-1beta/ACT-2/LD78/SCIF, MCP-1/MCAF, MCP-2, MCP-3, LDCF-1or LDCF-2
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/70596—Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/715—Assays involving receptors, cell surface antigens or cell surface determinants for cytokines; for lymphokines; for interferons
    • G01N2333/7158—Assays involving receptors, cell surface antigens or cell surface determinants for cytokines; for lymphokines; for interferons for chemokines
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/10—Musculoskeletal or connective tissue disorders
    • G01N2800/101—Diffuse connective tissue disease, e.g. Sjögren, Wegener's granulomatosis
    • G01N2800/102—Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
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  • Molecular Biology (AREA)
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  • General Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Rheumatology (AREA)
  • Rehabilitation Therapy (AREA)
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  • Tropical Medicine & Parasitology (AREA)
  • Virology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

Les lymphocytes T classiques (Tclass) CD4+ Foxp3 jouent un rôle clé dans le processus inflammatoire impliqué dans la polyarthrite rhumatoïde (PR). Il est maintenant de plus en plus clair que dans la PR, la stimulation de Tclass chronique n'induit pas un niveau suffisant d'épuisement pour inhiber leur réponse pathologique. Les objectifs des inventeurs ont été de déterminer si des récepteurs de SLAMF sont impliqués dans l'établissement de la réponse pro-inflammatoire de Tclass et si ces récepteurs représentent une protection contre l'épuisement de Tclass. Ainsi, les inventeurs ont obtenu des lymphocytes T du sang immunophénotypés provenant de patients PR (n = 64) et de donneurs sains (DS) (n = 14) à l'aide d'un panneau de cytométrie en flux à 13 marqueurs. L'expression de récepteurs de SLAMF a été déterminée parmi quatre sous-populations de Tclass ayant différents états d'activation (naïfs, mémoire centrale, mémoire effectrice et lymphocytes T CD4+ effecteurs à différenciation terminale). Pour évaluer le tropisme inflammatoire et la fonctionnalité de différentes sous-populations de Tclass, l'expression de CCR5 a été étudiée. Seule la fréquence des lymphocytes SLAMF4+ parmi les lymphocytes T de la mémoire effectrice (Tem ; CCR7-, CD45RA-) a été corrélée à l'activité de la maladie. Plus particulièrement, les inventeurs ont montré que seul SLAMF4+ Tem exprimant CCR5 était lié à l'activité PR. Les inventeurs ont révélé que SLAMF4+ CCR5+ Tem représente une sous-population de Tclass distincte résistante à l'inhibition médiée par PD-1 et fortement liée à l'activité PR.
PCT/EP2022/081802 2022-11-14 2022-11-14 Utilisation de la population de lymphocytes t cd4+ à mémoire effectrice slamf4+ ccr5+ en tant que biomarqueur dans la polyarthrite rhumatoïde WO2024104551A1 (fr)

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PCT/EP2022/081802 WO2024104551A1 (fr) 2022-11-14 2022-11-14 Utilisation de la population de lymphocytes t cd4+ à mémoire effectrice slamf4+ ccr5+ en tant que biomarqueur dans la polyarthrite rhumatoïde

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PCT/EP2022/081802 WO2024104551A1 (fr) 2022-11-14 2022-11-14 Utilisation de la population de lymphocytes t cd4+ à mémoire effectrice slamf4+ ccr5+ en tant que biomarqueur dans la polyarthrite rhumatoïde

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