WO2012103324A2 - Method for detection of intestinal, and blood-brain barrier permeability and testing materials thereto - Google Patents

Method for detection of intestinal, and blood-brain barrier permeability and testing materials thereto Download PDF

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Publication number
WO2012103324A2
WO2012103324A2 PCT/US2012/022706 US2012022706W WO2012103324A2 WO 2012103324 A2 WO2012103324 A2 WO 2012103324A2 US 2012022706 W US2012022706 W US 2012022706W WO 2012103324 A2 WO2012103324 A2 WO 2012103324A2
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WO
WIPO (PCT)
Prior art keywords
igg
iga
igm
brain barrier
protein
Prior art date
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Ceased
Application number
PCT/US2012/022706
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English (en)
French (fr)
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WO2012103324A3 (en
Inventor
Aristo Vojdani
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Immunosciences Lab Inc
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Immunosciences Lab Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to RU2013139476A priority Critical patent/RU2607479C2/ru
Priority to HK14102850.9A priority patent/HK1189938B/xx
Priority to AU2012211328A priority patent/AU2012211328A1/en
Priority to KR1020137022644A priority patent/KR101941308B1/ko
Priority to CN201280015809.0A priority patent/CN103460044B/zh
Priority to NZ614707A priority patent/NZ614707B2/en
Priority to BR112013019380A priority patent/BR112013019380A2/pt
Priority to MX2013008746A priority patent/MX2013008746A/es
Priority to JP2013551330A priority patent/JP6068362B2/ja
Priority to CA2828194A priority patent/CA2828194A1/en
Application filed by Immunosciences Lab Inc filed Critical Immunosciences Lab Inc
Priority to EP12739704.0A priority patent/EP2668498B1/en
Publication of WO2012103324A2 publication Critical patent/WO2012103324A2/en
Publication of WO2012103324A3 publication Critical patent/WO2012103324A3/en
Priority to IL227676A priority patent/IL227676A/en
Anticipated expiration legal-status Critical
Priority to AU2016259430A priority patent/AU2016259430B2/en
Priority to AU2016262726A priority patent/AU2016262726B2/en
Priority to IL250871A priority patent/IL250871B/en
Ceased legal-status Critical Current

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Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/564Immunoassay; 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/195Assays involving biological materials from specific organisms or of a specific nature from bacteria
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/06Gastro-intestinal diseases
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/70Mechanisms involved in disease identification
    • G01N2800/709Toxin induced

Definitions

  • the native gut-related antigen is preferably selected from the list consisting of: (1) an intestinal structural protein; (2) a tight junction protein; (3) a binding receptor to the tight junction protein; and (4) a cell junction protein.
  • testing occurs for antibodies to one or more of actin/actomyosin, occludin and/or zonulin, intestinal ZOT receptor, and matrix metalloproteinase-3 (MMP-3).
  • Figure 9 is a diagram showing a comparison of IgG, IgM and IgA against bacterial lipopolysaccharide and occludin/zonulin in healthy donors and patients with gastric autoimmunity.
  • the emphasis of the methodology of the present invention is on large molecules that are antigenic and which, upon their release from the barriers, have the capacity to challenge the immune system, resulting in the production of specific IgG, IgM and/or IgA antibodies against them, which are detected in blood, blood serum, and/or saliva samples.
  • the analytical procedure for IgG, IgM, and/or IgA antibody against LPS, intestinal and/or BBB proteins is now discussed.
  • all reagents were allowed to reach room temperature before the test assay was commenced.
  • the test assay procedure includes preparing the desired number of coated wells or plates with the desired number and type of antigens and/or peptides. Once the microtiter wells are prepared, about 100 ⁇ of 1 : 100 diluted control calibrator are added to Rows A and B of the microtiter plate as shown in Figure 7, which can be done using a multi-channel pipettor.
  • the plates were then incubated for about 60 minutes at room temperature. After incubation, the wells were then emptied and washed four times with PBS using an ELISA Washer. About 100 ⁇ of optimally diluted alkaline phosphatase-labeled goat anti-human IgA was added to the IgA plate or about 100 ⁇ of enzyme-labeled IgG was added to the IgG plate and anti-IgM was added to the IgM plate at optimal dilution.
  • Neurological examination revealed reduced corrected visual acuity of 6/48 in the right eye and 6/36 in the left eye with normal eye movements.
  • the patient had pyramidal weakness in both legs with mildly-based gait.
  • Pinprick examination demonstrated hemisensory level below D10 on both sides.
  • Vojdani A Vojdani E
  • Cooper EL Antibodies to myelin basic protein, myelin oligodendrocytes peptides, ⁇ - ⁇ -crystallin, lymphocyte activation and cytokine production in patients with multiple sclerosis. J Internal Med, 2003; 254: 363-74.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Cell Biology (AREA)
  • Analytical Chemistry (AREA)
  • Biotechnology (AREA)
  • Pathology (AREA)
  • Microbiology (AREA)
  • General Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Organic Chemistry (AREA)
  • Rehabilitation Therapy (AREA)
  • Rheumatology (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/US2012/022706 2011-01-28 2012-01-26 Method for detection of intestinal, and blood-brain barrier permeability and testing materials thereto Ceased WO2012103324A2 (en)

Priority Applications (15)

Application Number Priority Date Filing Date Title
HK14102850.9A HK1189938B (en) 2011-01-28 2012-01-26 Method for detection of intestinal, and blood-brain barrier permeability and testing materials thereto
AU2012211328A AU2012211328A1 (en) 2011-01-28 2012-01-26 Method for detection of intestinal, and blood-brain barrier permeability and testing materials thereto
KR1020137022644A KR101941308B1 (ko) 2011-01-28 2012-01-26 장, 혈액-뇌 장벽 투과성 검출 방법 및 테스트 물질
CN201280015809.0A CN103460044B (zh) 2011-01-28 2012-01-26 用于检测肠和血脑屏障通透性的方法及其测试材料
NZ614707A NZ614707B2 (en) 2011-01-28 2012-01-26 Method for detection of intestinal, and blood-brain barrier permeability and testing materials thereto
BR112013019380A BR112013019380A2 (pt) 2011-01-28 2012-01-26 método para detecção de permeabilidade da barreira hematoencefálica, e intestinal e materiais de teste da mesma
MX2013008746A MX2013008746A (es) 2011-01-28 2012-01-26 Metodo para la deteccion de permeabilidad intestinal y de la barrera hemato-encefalica y materiales de prueba para este.
CA2828194A CA2828194A1 (en) 2011-01-28 2012-01-26 Method for detection of intestinal, and blood-brain barrier permeability and testing materials thereto
JP2013551330A JP6068362B2 (ja) 2011-01-28 2012-01-26 腸および血液脳関門の透過性を検出する方法、およびその試験材料
RU2013139476A RU2607479C2 (ru) 2011-01-28 2012-01-26 Способ обнаружения проницаемости кишечного, а также гематоэнцефалического барьера и материалы для соответствующих тестов
EP12739704.0A EP2668498B1 (en) 2011-01-28 2012-01-26 Method for detection of intestinal, and blood-brain barrier permeability and testing materials thereto
IL227676A IL227676A (en) 2011-01-28 2013-07-28 A method for detecting permeability through the intestine and through a blood-brain barrier and substances for testing
AU2016259430A AU2016259430B2 (en) 2011-01-28 2016-11-18 Method for detection of intestinal, and blood-brain barrier permeability and testing materials thereto
AU2016262726A AU2016262726B2 (en) 2011-01-28 2016-11-24 Method for detection of intestinal, and blood-brain barrier permeability and testing materials thereto
IL250871A IL250871B (en) 2011-01-28 2017-03-01 A method for detecting permeability through the intestine and through the blood-brain barrier and testing substances from them

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161437244P 2011-01-28 2011-01-28
US61/437,244 2011-01-28

Publications (2)

Publication Number Publication Date
WO2012103324A2 true WO2012103324A2 (en) 2012-08-02
WO2012103324A3 WO2012103324A3 (en) 2012-11-01

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PCT/US2012/022706 Ceased WO2012103324A2 (en) 2011-01-28 2012-01-26 Method for detection of intestinal, and blood-brain barrier permeability and testing materials thereto

Country Status (12)

Country Link
US (2) US8663911B2 (enExample)
EP (1) EP2668498B1 (enExample)
JP (1) JP6068362B2 (enExample)
KR (1) KR101941308B1 (enExample)
CN (2) CN105823887B (enExample)
AU (3) AU2012211328A1 (enExample)
BR (1) BR112013019380A2 (enExample)
CA (2) CA2964555C (enExample)
IL (2) IL227676A (enExample)
MX (1) MX2013008746A (enExample)
RU (2) RU2016149216A (enExample)
WO (1) WO2012103324A2 (enExample)

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WO2015009907A1 (en) 2013-07-17 2015-01-22 The Johns Hopkins University A multi-protein biomarker assay for brain injury detection and outcome
CN107533048A (zh) 2015-02-05 2018-01-02 美国免疫阵列公司 用于诊断脑损伤或神经退行性变的方法和组合物
US11131676B2 (en) 2016-02-25 2021-09-28 The Trustees Of Columbia University In The City Of New York Systemic immune activation and biomarkers of nonceliac wheat/gluten sensitivity
CN105974105A (zh) * 2016-05-16 2016-09-28 河北艾驰生物科技有限公司 基质金属蛋白酶-3(mmp3)检测试剂盒
JP6782886B2 (ja) 2017-01-19 2020-11-11 国立大学法人島根大学 腸粘膜の透過性の診断薬、診断方法、診断装置
CN108191977B (zh) * 2017-12-25 2018-12-18 首都医科大学宣武医院 用于检测缺血性脑卒中血脑屏障早期损伤的抗体及其应用
CN108152492B (zh) * 2017-12-25 2019-03-08 首都医科大学宣武医院 用于检测缺血性脑卒中血脑屏障早期损伤的抗体及其应用
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