Diagnostic markers and therapeutic targets for Kawasaki disease

A technology for Kawasaki disease and biomarkers, which can be used in disease diagnosis, biological testing, biomaterial analysis, etc., and can solve problems such as increased morbidity

Inactive Publication Date: 2016-08-17
CHILDRENS MEDICAL CENT CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The absence of definitive diagnostic markers limits the accuracy of the clinical evaluation of suspected KD, thereby significantly increasing the incidence

Method used

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  • Diagnostic markers and therapeutic targets for Kawasaki disease
  • Diagnostic markers and therapeutic targets for Kawasaki disease
  • Diagnostic markers and therapeutic targets for Kawasaki disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0088] Example 1. Study Design, Participants and Results

[0089] The study was conducted in two periods. For the discovery period, urine samples from 6 patients with KD (including those with or without coronary artery dilatation) were compared with urine samples from 6 patients who were initially suspected of having KD but eventually diagnosed with a febrile illness mimicking KD. Compare. The discovery analysis also included 3 inter-individual control samples collected from KD patients after completion of treatment and resolution of symptoms. The validation phase recruited patients for whom evaluation for possible KD was made, but before a final diagnosis was made. Serum samples collected from an independent validation cohort collected as part of the Pediatric HeartNet Final Study of Kawasaki Disease. See Newburger et al., 356 New Engl. J. Med. 663 (2007).

[0090] Urine was collected as a clean collection sample for all study patients. Samples were labeled with study nu...

Embodiment 2

[0093] Example 2. Urine protein analysis and immunoassay

[0094] To discover candidate markers of KD, thawed 5 ml urine aliquots were fractionated using ultracentrifugation, protein precipitation, SDS-polyacrylamide gel electrophoresis, and reverse-phase liquid chromatography, as published in detail. Kentsis et al., 3 Proteomics Clin. Appl. 1052 (2009). Individual urine protein fractions were subjected to liquid chromatography tandem using a nanoflow HPLC system (Eksigent, Dublin, CA) coupled to a hybrid linear ion trap-Fourier transform ion cyclotron resonance mass spectrometer (LTQFT Ultra, Thermo Scientific, Waltham, MA). mass spectrum. For each MS / MS spectrum, the 200 strongest peaks were extracted by using MASCOT (version 2.1.04, Matrix Science) against the Human International Protein Index database (version 3.69, http: / / www.ebi.ac.uk / IPI ) to search. Assessment of identification accuracy was performed by searching the bait database consisting of the reversed protein...

Embodiment 3

[0104] Example 3. Urinary model of coronary arteries and meprin A immunohistochemistry

[0105] An established murine model of coronary arteritis based on intraperitoneal injection of group B Lactobacillus casei cell wall extract (LCWE). Lehman et al., 48 Clin. Immunol. Immunopathol. 108 (1988). L. casei group B was grown and cell wall extracts (LCWE) were prepared as described. Schulte et al., 183 J. Immunol 5311 (2009). Briefly, 6-week-old C57 / BL6 mice were injected with 250 μg LCWE in phosphate-buffered saline (PBS) or with saline alone. After 14 days, mice were sacrificed and coronary arteritis was identified in serial sections (7 [mu]m), fixed with formalin and stained with hematoxylin and eosin. For immunohistochemical analysis, sections were pretreated with 0.3% PBS in hydrogen peroxide for 30 min. Meprin A (clone F-20, Santa Cruz Biotech., Santa Cruz, CA) or isotype control antibody (goat serum, Santa Cruz Biotech.) was used 1:100 in bovine serum albumin with 0.5% ...

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Abstract

The present invention provides compositions and methods for the diagnosis and treatment of Kawasaki disease. More specifically, the proteome of KD patients is enriched in meprin A, filamin B, and filamin C, which serve as biomarkers (and potential therapeutic targets) for KD. Accordingly, detection of these biomarkers using the compositions and methods provided herein can inform the delivery of therapy to a subject.

Description

[0001] federal government funding [0002] This invention was made in part with Federal Government support under Grant Numbers U01HL068285, RR02172, U01HL068270, U01HL068269, U01HL068292, U01HL068290, U01HL068288, U01HL068281, and U01HL068279 awarded by the National Institutes of Health. The United States Federal Government has certain rights in this invention. [0003] Cross References to Related Applications [0004] This application claims the benefit of U.S. Provisional Application No. 61 / 475,936, filed April 15, 2011, and U.S. Provisional Application No. 61 / 579,007, filed December 22, 2011, under 35 U.S.C. § 119(e), the The contents of each of the US provisional applications are incorporated herein by reference in their entirety. technical field [0005] The present invention provides diagnostic markers and therapeutic targets related to Kawasaki disease (KD). More specifically, the proteome of KD patients is enriched in meprin A (meprin A), filamin B and filamin C, wh...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): G01N33/68
CPCG01N33/6893G01N2333/47G01N2333/96486G01N2800/328G01N2800/60G01N33/68G01N33/564
Inventor 亚历克斯·肯特赛斯苏姗·金汉诺·斯泰恩
Owner CHILDRENS MEDICAL CENT CORP
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