Application of reagent for inhibiting MHC-I and/or II signaling pathway in treatment of biliary atresia

A technology of MHC-II and MHC-I, applied in the field of biomedicine, which can solve problems such as undisclosed or verified

Pending Publication Date: 2022-05-06
GUANGZHOU WOMEN AND CHILDRENS MEDICAL CENTER
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, none of the above-mentioned documents has disclosed or verified: what indicators can be used to detect early and accurately whether there is BA-related immune damage and deal with it; how to diagnose, prevent and / or treat early or prognostic BA diseases to achieve Safe and accurate and effective purpose

Method used

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  • Application of reagent for inhibiting MHC-I and/or II signaling pathway in treatment of biliary atresia
  • Application of reagent for inhibiting MHC-I and/or II signaling pathway in treatment of biliary atresia
  • Application of reagent for inhibiting MHC-I and/or II signaling pathway in treatment of biliary atresia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0600] Example 1. Defects in B-cell production and self-tolerance lead to expansion of autoreactive B cells in children with BA

[0601] Existing studies have reported that the hematopoiesis of the liver occurs in the human fetal liver and will stop after birth (Holt and Jones, 2000). There is still a complete process of B cell development in the body.

[0602] method:

[0603] Single-cell RNA sequencing and analysis were performed on BA patients (n=6) and corresponding control liver tissues (selected from 6 cases of choledochal cyst and 6 cases of other diseases), to study the development of B cells and autoreactivity in the liver of children with BA The phenomenon of B cell expansion, in which, the distribution of cell subgroups at different stages of B cell development is analyzed using t-SNE diagrams, the gene expression of each B cell subgroup is displayed using violin plots, and the heat map is used to analyze the differences in B cell development Stage marker gene exp...

Embodiment 2

[0618] Example 2. Biliary atresia with high IgM / IgG4 ratio has a good prognosis

[0619] method:

[0620] By measuring the concentration of each subtype of immunoglobulin (including IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgD and IgE) in the serum of BA children (26 cases) after Kasai operation, and then detecting all types of IgM and IgE in serum IgG4, and the ratio of IgM / IgG4 was compared to evaluate the prognosis of BA patients after Kasai operation.

[0621] result:

[0622] figure 2 It is the survival curve of BA children with high IgM / IgG4 ratio and low IgM / IgG4 ratio in serum after Kasai operation; the high and low ratios are obtained through bioinformatics cluster analysis and classification of 26 children.

[0623] Depend on figure 2 It can be seen that the jaundice-free survival probability of BA children with high IgM / IgG4 ratio (13 cases) is about 62.5%, and the jaundice-free survival probability of BA children with low IgM / IgG4 ratio (13 cases) is about 12.5%. A...

Embodiment 3

[0626] Example 3. Increased Ro / SSA-specific IgG is an indication of biliary atresia

[0627] method:

[0628] ELISA was used to detect and quantify IgM (DsDNA-specific IgM, Nucleosome-specific IgM, RNP-specific IgM, Ro / SSA-specific IgM), Ro / SSA-specific self-reactive IgG concentration, and comparative analysis.

[0629] Result description:

[0630] image 3 It is the IgM and IgG concentrations in serum and liver of BA children, CC control group and other control groups. Depend on image 3 It can be seen that the concentrations of various IgMs (including DsDNA-specific IgM, Nucleosome-specific IgM, RNP-specific IgM, and Ro / SSA-specific IgM) in BA children were significantly lower than those in CC controls. group and other control groups, showing a significant difference (P Figure 4 Shown: Ro / SSA-specific autoreactive IgG can be very effective in distinguishing BA subjects from CC cases (AUC=0.767), and Ro / SSA-specific autoreactive IgG can be used as one of the diagnostic ...

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Abstract

The invention relates to the field of biomedicine, in particular to application of a reagent for inhibiting MHC-I and / or II signal channels in treatment of biliary atresia. According to the present invention, the research on the BA disease model induced by infection of rhesus rotavirus (RRV) on young rats discovers that the reagent for inhibiting the MHC-I and / or II signal channel can significantly reduce the liver injury degree and inhibit the BA disease progress, such that the clinical value of the reagent for inhibiting the MHC-I and / or II signal channel in BA treatment is confirmed.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to the application of a reagent for inhibiting MHC-I and / or II signaling pathways in the treatment of biliary atresia. Background technique [0002] Biliary atresia (BA) occurs during the perinatal period of infants (for example, from 28 weeks of pregnancy to 4 weeks after birth), and the incidence rate varies from 1 / 5000 to 1 / 18000 in different countries and regions. Its etiology and pathogenesis are still unknown, and it is generally believed to be jointly determined by developmental and / or environmental factors (such as viral infection, etc.), manifested as jaundice and liver failure caused by severe cholangitis-mediated extrahepatic bile duct obstruction, and the prognosis is poor , high fatality rate. The basic pathological changes of biliary atresia are, for example, progressive inflammation of intrahepatic and external bile ducts, liver fibrosis, and liver cirrhosis. T...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K39/395A61P1/16
CPCA61K45/00A61K39/3955A61P1/16A61K39/395A61K38/00
Inventor 张玉霞徐艳慧陈章华王俊林泽锋夏慧敏
Owner GUANGZHOU WOMEN AND CHILDRENS MEDICAL CENTER
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