WO2020043693A1 - Diagnostic de la sclérose en plaques - Google Patents

Diagnostic de la sclérose en plaques Download PDF

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Publication number
WO2020043693A1
WO2020043693A1 PCT/EP2019/072775 EP2019072775W WO2020043693A1 WO 2020043693 A1 WO2020043693 A1 WO 2020043693A1 EP 2019072775 W EP2019072775 W EP 2019072775W WO 2020043693 A1 WO2020043693 A1 WO 2020043693A1
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WO
WIPO (PCT)
Prior art keywords
cells
level
ratio
monocytes
detected
Prior art date
Application number
PCT/EP2019/072775
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English (en)
Inventor
Gerd MEYER ZU HOERSTE
Heinz Wiendl
Sven MEUTH
Original Assignee
Westfälische Wilhelms-Universität Münster
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Application filed by Westfälische Wilhelms-Universität Münster filed Critical Westfälische Wilhelms-Universität Münster
Publication of WO2020043693A1 publication Critical patent/WO2020043693A1/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
    • G01N33/569—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
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
    • G01N2333/70514—CD4
    • 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
    • G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
    • G01N2333/70517—CD8
    • 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
    • G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
    • G01N2333/70535—Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)
    • 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
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/28—Neurological disorders
    • G01N2800/285—Demyelinating diseases; Multipel sclerosis

Definitions

  • the objective of the present invention is to comply with this need.
  • Also comprised by the present invention may be the method as defined elsewhere herein, wherein detecting the level of NK cells comprises measuring CD45, CD16 and/or CD56; wherein detecting the level of CD4 + T cells comprises measuring CD45, CD3 and/or CD4; wherein detecting the level of B cells comprises measuring CD45, CD19 and/or CD138; wherein detecting the level of CD8 + T cells comprises measuring CD45, CD3 and/or CD8; wherein detecting the level of CD14 + CD16 monocytes comprises measuring CD45, CD14 and/or CD16; and/or wherein detecting the level of CD14 + CD16 + monocytes comprises measuring CD45, CD14 and/or CD16.
  • CSF cerebrospinal fluid
  • Fig. 3 Late B lineage cells accumulate in the CSF in MS.
  • Fig. 6 Patient characteristics.
  • Fig. 11 Calculation of four different composite scores of treatment-na ' fve patients with relapsing-remitting multiple sclerosis in comparison to patients suffering from idiopathic intracranial hypertension as a control.
  • CSF cerebrospinal fluid
  • MS multiple sclerosis
  • CNS central nervous system
  • MS has also been classified as an autoimmune disease. It refers to a demyelinating disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged.
  • MS disease activity can be monitored by cranial scans, including magnetic resonance imaging (MRI) of the brain, accumulation of disability, as well as rate and severity of relapses.
  • MRI magnetic resonance imaging
  • Said adjustment factor being multiplied with the ratio of the level of CD8+ T cells to the level of CD4+ T cells may be at least about 2, at least about 2.2, at least about 2.5, at least about 3.0, at least about 3.3, at least about 3.5, at least about 3.6; or be any number in the range of about 2 to about 8, preferably about 2.2 to about 6.7, preferably about 2.5 to about 5.7, preferably about 3.0 to about 4.8, preferably about 3.3 to about 4.4, preferably about 3.5 to about 4.2, preferably about 3.6 to about 4.0, or most preferably about 2, about 2.1 , about 2.2, about 2.3, about 2.4, about 2.5, about 2.7, about 2.8, about 2.9, about 3.0, about 3.1 , about 3.2, about 3.3, about 3.4, about 3.5, about 3.6, about 3.7, about 3.8, about 3.81 , about 3.82, about 3.83, about 3.84, about 3.85, about 3.9, about 4.0, about 4.1 ,
  • said specific cell levels may be detected by using a flow cytometry device, preferably using flow cytometry analysis being combined with immunofluorescence as described elsewhere herein.
  • said flow cytometry device as defined above may be a FACS.
  • said FACS may be connected to a computer, tablet, smartphone or any other technical device / apparatus being used as a further means for performing said FACS analysis.
  • said FACS may not be connected to a computer, tablet, smartphone or any other technical device / apparatus being used as a further means for performing said FACS analysis.
  • the present invention also envisages a computer program comprising instructions to cause the data processing system as defined in [00152] or the flow cytometry device as defined in [00156] above to execute the steps of
  • the control group consisted of 22 patients diagnosed with idiopathic intracranial hypertension (IIH) (Tab. 2). Patients were recruited and processed in three consecutive cohorts. CSF cells from cohort 1 were used for unsorted single cell RNA-seq (6 IIH vs. 6 MS patients). CSF cells from cohort 2 were analysed by flow cytometry only (7 IIH vs. 11 MS patients), and from cohort 3 were flow sorted for RNA-seq of CD3 + CD4 + CXCR5 + TFH cells (9 IIH vs. 9 MS patients). Patient details are provided in Table 2 and Figure 6. All patients gave written informed consent. The study was performed in accordance with the declaration of Helsinki and approved by the local ethics committees.
  • Exclusion criteria for all patients were: 1 ) immunologically relevant co-morbidities (e.g. rheumatologic diseases), 2) severe concomitant infectious diseases (e.g. HIV, meningitis, encephalitis), 3) pregnancy or breastfeeding, 4) younger than 18 years, 5) mental illness impairing the ability to give informed consent, 6) artificial blood contamination during the lumbar puncture resulting in >200 red blood cells / mI in routine CSF analysis.
  • MS patients whose diagnostic work-up revealed a diagnosis other than MS within four weeks of clinical follow-up were retrospectively excluded from the study.
  • the recruitment algorithm is illustrated in Figure 6C.

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Cell Biology (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Virology (AREA)
  • Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Zoology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

La présente invention concerne un procédé de diagnostic d'un sujet atteint de sclérose en plaques qui comprend la détermination de différents rapports cellulaires dans un échantillon de liquide céphalorachidien (LCR) de test obtenu à partir dudit sujet, la combinaison desdits rapports cellulaires spécifiques indiquant si ledit sujet souffre ou non de la sclérose en plaques. En outre, la présente invention concerne un système de traitement de données comprenant un processeur conçu pour effectuer les étapes dudit procédé ci-dessus, un dispositif de cytométrie en flux capable de détecter les niveaux de cellules spécifiques dans un échantillon de LCR de test comprenant le système de traitement de données défini, un programme informatique comprenant des instructions destinées à amener le système de traitement de données ou le dispositif de cytométrie en flux à exécuter les étapes du procédé défini, ainsi qu'un support lisible par ordinateur sur lequel est stocké le programme informatique tel que défini. La présente invention concerne également un kit et un agent destinés à être utilisés dans le traitement de la sclérose en plaques.
PCT/EP2019/072775 2018-08-29 2019-08-27 Diagnostic de la sclérose en plaques WO2020043693A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
LULU100915 2018-08-29
LU100915 2018-08-29

Publications (1)

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WO2020043693A1 true WO2020043693A1 (fr) 2020-03-05

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022207748A1 (fr) * 2021-03-30 2022-10-06 Westfälische Wilhelms-Universität Münster Classification de manifestations de maladie neurologique ou psychiatrique à l'aide d'une analyse multidimensionnelle de liquide céphalorachidien
CN115290875A (zh) * 2022-08-15 2022-11-04 无锡市人民医院 一种6色tbnk淋巴细胞亚群检测试剂盒和检测方法
EP4379375A1 (fr) * 2022-12-01 2024-06-05 Universität Münster Classification de maladie du tissu conjonctif avec manifestation neurologique par analyse multidimensionnelle du sang périphérique

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022207748A1 (fr) * 2021-03-30 2022-10-06 Westfälische Wilhelms-Universität Münster Classification de manifestations de maladie neurologique ou psychiatrique à l'aide d'une analyse multidimensionnelle de liquide céphalorachidien
CN115290875A (zh) * 2022-08-15 2022-11-04 无锡市人民医院 一种6色tbnk淋巴细胞亚群检测试剂盒和检测方法
EP4379375A1 (fr) * 2022-12-01 2024-06-05 Universität Münster Classification de maladie du tissu conjonctif avec manifestation neurologique par analyse multidimensionnelle du sang périphérique

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