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Methods and systems for selection and treatment of patients with inflammatory diseases

An inflammatory disease, active technology, applied in the field of selection and treatment of inflammatory disease patients and systems, can solve the problem of less personalized therapy

Pending Publication Date: 2021-02-12
CEDARS SINAI MEDICAL CENT +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, very few personalized therapies are available to patients

Method used

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  • Methods and systems for selection and treatment of patients with inflammatory diseases
  • Methods and systems for selection and treatment of patients with inflammatory diseases
  • Methods and systems for selection and treatment of patients with inflammatory diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[1246] Example 1: Identification of Genotypes

[1247] IBD patients were recruited at the Cedars-Sinai Inflammatory Bowel Disease Centers. The diagnosis of each patient was based on standard endoscopic, histological, and radiographic features. Blood samples were collected from patients at enrollment. Blood samples were also collected from individuals without IBD. All samples collected were genotyped at Cedars-Sinai Medical Center using Illumina whole genome arrays following the manufacturer's protocol (Illumina, San Diego, CA). Markers / SNPs were excluded from analysis if: there was a deviation in the Hardy–Weinberg balance in controls, p ≤ 0.0001; there was >2% defect in the SNP, and the minor allele frequency was 0.25) and excluded from analysis (PLINK). Generate race proportion estimates for all individuals using a mixture. Only subjects identified as Caucasian by admixture (proportion <0.75) were included in the analysis.

[1248] Multiple studies involving inflammator...

Embodiment 2

[1249] Example 2: eQTL in small bowel resection identifies polymorphisms as functionally associated with CD30L protein expression

[1250] Eighty-five Caucasian patients with Crohn's disease (CD) who underwent small bowel resection were recruited at the Cedars-Sinai Inflammatory Bowel Disease Centers. The diagnosis of each patient was based on standard standard endoscopic, histological, and radiographic features. Patients were selected on the basis of being diagnosed with CD and having undergone small bowel resection for the disease. Tissue biopsy samples were collected from uninvolved tissue sections resected from the small bowel after surgery. Expression quantitative trait locus mapping (eQTL) was performed on these samples. Table 13 provides polymorphisms associated with reduction of CD30. Table 14 provides polymorphisms associated with increased CD30. In tissue samples, a negative beta value indicates a decrease in gene expression, while a positive beta value indicates...

Embodiment 3

[1251] Example 3. Polymorphic expression affects the expression and function of CD30L and pro-inflammatory cytokines in peripheral blood

[1252] Crohn's disease (CD) patients were recruited at the Cedars-Sinai Inflammatory Bowel Disease Centers. The diagnosis of each patient was based on standard endoscopic, histological, and radiographic features. Patients were selected on the basis of being diagnosed with CD. Peripheral blood samples were collected from patients at enrollment. Peripheral blood mononuclear cells (PBMC) were isolated on standard Ficoll-Hypaque density gradients. PBMCs were stimulated in vitro for 72 hours under conditions that upregulated CD30L (phorbol 12-myristate 13-acetate (PMA) and ionomycin) or CD30 (anti-CD3 antibody and anti-CD28 antibody). Supernatants were collected at 6, 24 and 72 hours for cytokine analysis, and cells were collected after 72 hours and analyzed for CD30 and CD30L expression by flow cytometry. In subjects carrying (homozygous or...

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Abstract

Described herein are methods and systems for identifying subjects suitable for treatment with an inhibitor of CD30L activity or expression, such as an anti-CD30L antibody. Methods and systems disclosed herein identify subjects suitable for treatment based on a presence of a genotype that is indicative of a disease or condition in the subject for which an inhibitor of CD30L is a suitable treatment.Exemplary conditions include both Crohns disease and primary sclerosing cholangitis. Compositions used to detect the genotypes described herein, and methods of using them are also provided.

Description

[0001] cross reference [0002] This application claims U.S. Provisional Application Serial No. 62 / 664,720 filed April 30, 2018, U.S. Provisional Application Serial No. 62 / 681,557 filed June 6, 2018, and U.S. Provisional Application Serial No. 62 filed December 21, 2018 / 784,179, all of which are hereby incorporated by reference in their entirety. [0003] sequence listing [0004] This application contains a Sequence Listing, which has been filed electronically in ASCII format, and is hereby incorporated by reference in its entirety. Said ASCII copy, created on April 19, 2019, is named 52388-740_601_SL.txt and is 7,862,716 bytes in size. Background technique [0005] Inflammatory, fibrostenotic, and fibrotic diseases constitute a significant health burden worldwide due to the large number of affected individuals, diverse disease pathogenesis, and variable clinical presentation. One such disease is inflammatory bowel disease (IBD), which comes in two common forms: Crohn'...

Claims

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Application Information

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IPC IPC(8): C07K16/24A61K39/395C12Q1/6883
CPCC07K16/2875A61K2039/505A61P37/06A61P29/00C12Q1/6883C12Q2600/106C12Q2600/156A61P1/00
Inventor J·比尔斯伯勒D·P·麦戈文斯蒂芬·塔尔干阿尔卡·波达杰弗里·D·沃特金斯辛迪·T·迪克森
Owner CEDARS SINAI MEDICAL CENT
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