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1. (WO2019048569) METHODS AND KITS FOR DIAGNOSIS OF FAMILIAL MEDITERRANEAN FEVER
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Pub. No.: WO/2019/048569 International Application No.: PCT/EP2018/074053
Publication Date: 14.03.2019 International Filing Date: 06.09.2018
IPC:
G01N 33/68 (2006.01) ,G01N 33/569 (2006.01) ,G01N 33/564 (2006.01)
G PHYSICS
01
MEASURING; TESTING
N
INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33
Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48
Biological material, e.g. blood, urine; Haemocytometers
50
Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
68
involving proteins, peptides or amino acids
G PHYSICS
01
MEASURING; TESTING
N
INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33
Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48
Biological material, e.g. blood, urine; Haemocytometers
50
Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
53
Immunoassay; Biospecific binding assay; Materials therefor
569
for micro-organisms, e.g. protozoa, bacteria, viruses
G PHYSICS
01
MEASURING; TESTING
N
INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
33
Investigating or analysing materials by specific methods not covered by groups G01N1/-G01N31/131
48
Biological material, e.g. blood, urine; Haemocytometers
50
Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
53
Immunoassay; Biospecific binding assay; Materials therefor
564
for pre-existing immune complex or autoimmune disease
Applicants:
INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) [FR/FR]; 101, rue de Tolbiac 75013 Paris, FR
UNIVERSITÉ CLAUDE BERNARD - LYON 1 [FR/FR]; 43 Boulevard du 11 novembre 1918 69100 Villeurbanne, FR
ENS - ECOLE NORMALE SUPÉRIEURE DE LYON [FR/FR]; 46, Allée d'Italie 69007 Lyon, FR
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS) [FR/FR]; 3, Rue Michel Ange 75016 Paris, FR
HOSPICES CIVILS DE LYON [FR/FR]; 69002 Lyon, FR
Inventors:
HENRY, Thomas; FR
JAMILLOUX, Yvan; FR
LEFEUVRE, Lucie; FR
MARTIN, Amandine; FR
MAGNOTTI, Flora; FR
BELOT, Alexandre; FR
Agent:
INSERM TRANSFERT; 7 rue Watt 75013 Paris, FR
Priority Data:
17306158.107.09.2017EP
Title (EN) METHODS AND KITS FOR DIAGNOSIS OF FAMILIAL MEDITERRANEAN FEVER
(FR) PROCÉDÉS ET TROUSSES POUR LE DIAGNOSTIC DE LA FIÈVRE MÉDITERRANÉENNE FAMILIALE
Abstract:
(EN) The present invention relates to a non-invasive, specific and rapid diagnostic method of Familial Mediterranean fever (FMF) in a subject said method comprising the step of measuring the level of cytokine (IL-18 or IL-1 beta) secreted by immune primary cells (or cell death level of these cells) obtained from said subject, which have been beforehand treated with a Protein Kinase C (PKC) inhibitor, and optionally beforehand treated with a NF-kB activator such as LPS. Inventors show based on the extensive study of the inflammasome process of the monocytes, that PKC superfamily inhibitors trigger inflammasome activation in monocytes from FMF patients while they are not sufficient to do so in monocytes from healthy donors (HD) or from patient having hyperimmunoglobulinemia D syndrome (HIDS). Using cytokine release quantification or determination of real time cell death kinetics, inventors demonstrate that PKC superfamily inhibitors can discriminate FMF patients from HD or from patients with systemic inflammation from other aetiologies. These results thus set-up the basis for the development of a rapid functional specific diagnostic test for FMF. Methods of treatment are disclosed.
(FR) La présente invention concerne un procédé de diagnostic non invasif, spécifique et rapide de la fièvre méditerranéenne familiale (FMF) chez un sujet, ledit procédé comprenant l’étape de mesure du taux de cytokine (IL-18 ou IL-1 bêta) secrété par des cellules primaires immunitaires (ou le taux de mort cellulaire de ces cellules) obtenues à partir dudit sujet, qui ont été préalablement traitées avec un inhibiteur de protéine Kinase C (PKC), et éventuellement traitées préalablement avec un activateur de NF-kB tel que LPS. Les inventeurs ont démontré, sur la base de l’étude approfondie du processus d’inflammasome des monocytes, que les inhibiteurs de la superfamille PKC déclenchent l’activation de l’inflammasome dans les monocytes de patients atteints de FMF tandis qu’ils n’ont pas une action suffisante pour cela dans des monocytes de donneurs sains (HD) ou d’un patient ayant un syndrome d’hyperimmunoglobulinémie D (HIDS). Au moyen d’une quantification ou détermination de libération de cytokines de cinétique de mort cellulaire en temps réel, les inventeurs démontrent que des inhibiteurs de la superfamille PKC peuvent distinguer des patients atteints de FMF HD ou de patients présentant une inflammation systémique d’autres étiologies. Ces résultats établissent ainsi la base du développement d’un test de diagnostic spécifique fonctionnel rapide pour FMF. L’invention concerne en outre des procédés de traitement.
Designated States: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW
African Regional Intellectual Property Organization (ARIPO) (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Office (AM, AZ, BY, KG, KZ, RU, TJ, TM)
European Patent Office (EPO) (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG)
Publication Language: English (EN)
Filing Language: English (EN)