CN115166250A - Use of T cells as biomarkers for monitoring or predicting the efficacy of anti-HBV treatment or predicting the risk of relapse - Google Patents
Use of T cells as biomarkers for monitoring or predicting the efficacy of anti-HBV treatment or predicting the risk of relapse Download PDFInfo
- Publication number
- CN115166250A CN115166250A CN202210842043.9A CN202210842043A CN115166250A CN 115166250 A CN115166250 A CN 115166250A CN 202210842043 A CN202210842043 A CN 202210842043A CN 115166250 A CN115166250 A CN 115166250A
- Authority
- CN
- China
- Prior art keywords
- cells
- cxcr5
- relapse
- predicting
- group
- Prior art date
- Legal status (The legal status 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 status listed.)
- Pending
Links
- 210000001744 T-lymphocyte Anatomy 0.000 title claims abstract description 80
- 238000011282 treatment Methods 0.000 title claims abstract description 38
- 238000012544 monitoring process Methods 0.000 title claims abstract description 12
- 239000000090 biomarker Substances 0.000 title claims abstract description 9
- 102100031658 C-X-C chemokine receptor type 5 Human genes 0.000 claims abstract description 44
- 101000922405 Homo sapiens C-X-C chemokine receptor type 5 Proteins 0.000 claims abstract description 44
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 claims abstract description 43
- 210000003289 regulatory T cell Anatomy 0.000 claims abstract description 28
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 10
- 230000035876 healing Effects 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 claims description 24
- 210000004027 cell Anatomy 0.000 claims description 22
- 230000000694 effects Effects 0.000 claims description 16
- 230000002829 reductive effect Effects 0.000 claims description 12
- 210000005259 peripheral blood Anatomy 0.000 claims description 8
- 239000011886 peripheral blood Substances 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 229960004556 tenofovir Drugs 0.000 claims description 7
- 230000007423 decrease Effects 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 5
- 238000011284 combination treatment Methods 0.000 claims description 2
- 208000002672 hepatitis B Diseases 0.000 abstract description 30
- 208000000419 Chronic Hepatitis B Diseases 0.000 abstract description 24
- 230000000840 anti-viral effect Effects 0.000 abstract description 11
- 108010050904 Interferons Proteins 0.000 abstract description 5
- 102000014150 Interferons Human genes 0.000 abstract description 5
- 229940079322 interferon Drugs 0.000 abstract description 5
- 238000009826 distribution Methods 0.000 description 17
- 108010092851 peginterferon alfa-2b Proteins 0.000 description 12
- 241000700721 Hepatitis B virus Species 0.000 description 11
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 10
- 238000011160 research Methods 0.000 description 10
- 239000000427 antigen Substances 0.000 description 9
- 102000036639 antigens Human genes 0.000 description 9
- 108091007433 antigens Proteins 0.000 description 9
- 230000008859 change Effects 0.000 description 8
- 238000001514 detection method Methods 0.000 description 5
- 238000005206 flow analysis Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 102100025277 C-X-C motif chemokine 13 Human genes 0.000 description 4
- 101000858064 Homo sapiens C-X-C motif chemokine 13 Proteins 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 230000001276 controlling effect Effects 0.000 description 4
- 230000003325 follicular Effects 0.000 description 4
- 238000007710 freezing Methods 0.000 description 4
- 230000008014 freezing Effects 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 108091036055 CccDNA Proteins 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- 230000005867 T cell response Effects 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 3
- 238000007405 data analysis Methods 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 3
- 210000002443 helper t lymphocyte Anatomy 0.000 description 3
- 210000002865 immune cell Anatomy 0.000 description 3
- 230000007365 immunoregulation Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 101710142246 External core antigen Proteins 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 210000001280 germinal center Anatomy 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 210000001806 memory b lymphocyte Anatomy 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 210000004180 plasmocyte Anatomy 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 210000005212 secondary lymphoid organ Anatomy 0.000 description 2
- 238000012353 t test Methods 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 208000022309 Alcoholic Liver disease Diseases 0.000 description 1
- 108050006947 CXC Chemokine Proteins 0.000 description 1
- 102000019388 CXC chemokine Human genes 0.000 description 1
- 101710132601 Capsid protein Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010057573 Chronic hepatic failure Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 208000010334 End Stage Liver Disease Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 101001045751 Homo sapiens Hepatocyte nuclear factor 1-alpha Proteins 0.000 description 1
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 1
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 1
- 101100369992 Homo sapiens TNFSF10 gene Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000035999 Recurrence Diseases 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 108700012411 TNFSF10 Proteins 0.000 description 1
- 102100024598 Tumor necrosis factor ligand superfamily member 10 Human genes 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000008649 adaptation response Effects 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000011444 chronic liver failure Diseases 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000007771 core particle Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000009615 deamination Effects 0.000 description 1
- 238000006481 deamination reaction Methods 0.000 description 1
- 230000005860 defense response to virus Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 208000028208 end stage renal disease Diseases 0.000 description 1
- 201000000523 end stage renal failure Diseases 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000008713 feedback mechanism Effects 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 210000004475 gamma-delta t lymphocyte Anatomy 0.000 description 1
- 208000005252 hepatitis A Diseases 0.000 description 1
- 201000010284 hepatitis E Diseases 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 108091008042 inhibitory receptors Proteins 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000003519 mature b lymphocyte Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 108010092853 peginterferon alfa-2a Proteins 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- 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
- G01N33/576—Immunoassay; Biospecific binding assay; Materials therefor for hepatitis
- G01N33/5761—Hepatitis B
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
-
- 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
- G01N33/558—Immunoassay; Biospecific binding assay; Materials therefor using diffusion or migration of antigen or antibody
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/10—Investigating individual particles
- G01N15/14—Optical investigation techniques, e.g. flow cytometry
- G01N2015/1486—Counting the particles
-
- 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
- G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses
- G01N2333/01—DNA viruses
- G01N2333/02—Hepadnaviridae, e.g. hepatitis B virus
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- General Health & Medical Sciences (AREA)
- Pathology (AREA)
- Cell Biology (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Communicable Diseases (AREA)
- Zoology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Dispersion Chemistry (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The invention discloses the use of T cells as biomarkers in the preparation of products for monitoring or predicting the efficacy of anti-HBV therapy, said T cells including Treg cells, CD4+ T cells, CD8+ T cells; also disclosed is the use of T cells as biomarkers for the preparation of a product for predicting the risk of recurrence after clinical functional healing in anti-HBV therapy, said T cells comprising CD8+ subset CXCR5+ CD8+ T cells and CD4+ subset CXCR5+ CD4+ T cells. The invention can be applied to guide chronic hepatitis B interferon antiviral treatment, provides a new immune target for exploring chronic hepatitis B antiviral treatment, improves the cure rate and reduces the recurrence rate.
Description
Technical Field
The invention relates to the technical field of biomedicine, in particular to application of T cells as biomarkers in monitoring or predicting the curative effect of anti-HBV treatment or predicting the risk of relapse.
Background
Chronic Hepatitis B (CHB) is a type of infectious disease caused by Hepatitis B Virus (HBV) that seriously jeopardizes public life safety. The treatment of chronic hepatitis B aims to reduce the occurrence of cirrhosis, liver failure and HCC, improve the life quality of patients and prolong the survival time. The actual functional cure is the aim currently pursued by medical workers, and the functional cure is different from inactive HBV carriers after drug withdrawal, namely HBsAg negative conversion, anti-HBs negative or positive, HBeAg negative, serum HBVDNA is lower than the lower detection limit, and the risk of HCC is reduced along with time; the distinction from "complete cure" is that the intrahepatic cccDNA is still in a detectable state but inactive. The first-line medicine polyethylene glycol interferon (Peg-IFN) for clinical cure has a direct antiviral and immunoregulation dual-action mechanism, can obviously improve the HBsAg loss rate of patients with chronic hepatitis B, can block the formation of core particles in the antiviral action, regulates and controls cccDNA epigenetics, and ISGs-mediated antiviral defense in infected cells and non-infected cells, thereby achieving the purposes of reducing HBVDNA and reducing the expression of HBV antigens (HBsAg, HBcAg and HBeAg); in the action of immune regulation, the TRAIL expression of NK cells can be increased, CD56brihgt NK cells are activated, CD8+ T cell response is increased slightly and CD4+ T cell response is regulated, so that the generation of IFN-gamma for direct antivirus is enhanced, T cell response is promoted, and finally the effect of clinical cure is achieved. While the study by WuD et al suggests that: the antiviral immunity efficacy of the reshaped organism is the future of patients with chronic hepatitis B by combining multi-target intervention of immunoregulation on the basis of continuous virus control. In recent years, more and more attention is paid to researchers in immunoregulation research. XiaY et al believe that T cell-produced IFN- γ and TNF- α can reduce HBVcccDNA by inducing deamination and subsequent cccDNA decay; wang et al believe that the interaction mechanism of Foxp3 (a surface marker for Tregs) and IL-17/IL-23 may become a new point of breakthrough for HBV clearance, and that Foxp3 is positively associated with HBVDNA and HBsAg.
While in CHB, CXCL13 and IL-21 axis activation have a significant correlation with the occurrence of functional healing. Shen Z et al have demonstrated through animal models that IL-21 and IL-33 are closely associated with the clearance of HBV. The C-X-C chemokine receptor5 (CXCR 5) and the homologous receptor CXCL13 are members of CXC subtype in chemokine superfamily, can chemotactic mature B cells and T follicular helper cells to migrate to B cell follicles and growth centers and secrete memory B cells and plasma cells. The subgroup of CD8+ T cells CXCR5+ CD8+ T cell follicular cytotoxic T cells play an important role in controlling chronic viral infections. The research of the group of the Red teaching questions found that: the proportion of gamma delta T cells is positively correlated with HBV replication and negatively correlated with the inflammation degree of the liver, and the lower the proportion of the effector memory subgroup is, the better the curative effect of Peg-IFN alpha-2 a on the CHB combined with TDF is.
In conclusion, a plurality of researches prove to the people that the importance of enhancing the host immune function in the combination of Peg-IFN and TDF anti-HBV treatment is one of the key factors for improving the clinical cure rate of chronic hepatitis B. However, after clinical functional cure is achieved, about 9.6% of patients have recurrence, i.e. positive HBsAg or positive HBV-DNA. Therefore, the research on the difference between relapse and non-relapse has important significance for guiding chronic hepatitis B interferon antiviral treatment, providing a new immune target for exploring chronic hepatitis B antiviral treatment, improving the cure rate and reducing the relapse rate.
Disclosure of Invention
One of the objects of the present invention is to provide the use of T cells including Treg cells, CD4+ T cells, CD8+ T cells as biomarkers for the preparation of a product for monitoring or predicting the efficacy of anti-HBV therapy.
In the above technical scheme, the changes of the CD4+ T cell content, treg cell content and CD4/CD8 ratio are used to predict or monitor the efficacy of anti-HBV treatment; compared with a reference, the content of CD4+ T cells of the subject is remarkably reduced, the CD4/CD8 ratio shows a remarkably reduced trend, the content of Treg cells is remarkably reduced, and the medicine has a curative effect, and vice versa; preferably, the reference is the normal population and/or the cell content of the subject prior to administration.
It is another object of the invention to provide the use of T cells comprising CD8+ subgroup CXCR5+ CD8+ T cells and CD4+ subgroup CXCR5+ CD4+ T cells as a biomarker for the manufacture of a product for predicting the risk of relapse after reaching a clinically functional cure in anti-HBV therapy.
In the above-described protocol, a significant decrease in CXCR5+ CD8+ T cells and CXCR5+ CD4+ T cells in the subject, as compared to the reference in the non-relapsed group, is indicative of a high risk of HBsAg relapse, whereas a high level of occupancy in T cells by CXCR5+ CD8+ T cells and CXCR5+ CD4+ T cells is indicative of no or low risk of relapse.
It is a further object of the present invention to provide the use of an agent for detecting the amount of Treg cells, CD4+ T cells, CD8+ T cells in the manufacture of a product for monitoring or predicting the efficacy of an anti-HBV treatment.
In the technical scheme, the change of the content of CD4+ T cells, the content of Treg cells and the ratio of CD4/CD8 is used for predicting or monitoring the curative effect of anti-HBV treatment; compared with the reference, the content of CD4+ T cells of the subject is obviously reduced, the CD4/CD8 ratio shows a trend of obviously reducing, the content of Treg cells is obviously reduced, and the medicine has the curative effect, and vice versa.
Still another object of the present invention is to provide the use of a substance for detecting the amount of CD8+ subgroup CXCR5+ CD8+ T cells and CD4+ subgroup CXCR5+ CD4+ T cells in the manufacture of a product for predicting the risk of recurrence after clinical functional cure in anti-HBV treatment.
In the above-described protocol, a significant decrease in CXCR5+ CD8+ T cells and CXCR5+ CD4+ T cells in the subject, as compared to the reference in the non-relapsed group, is indicative of a high risk of HBsAg relapse, whereas a high level of occupancy in T cells by CXCR5+ CD8+ T cells and CXCR5+ CD4+ T cells is indicative of no or low risk of relapse.
In the above application technical scheme, the T cell refers to a T cell in peripheral blood; the anti-HBV treatment is Peg-IFN treatment, preferably combination treatment of Peg-IFN and tenofovir.
The substance is selected from antibody and chip.
The beneficial effects of the invention are:
according to the invention, after the Peg-IFN alpha and TDF are combined to treat chronic hepatitis B to achieve clinical functional cure, the influence of various immune cell functions on clinical relapse and the difference between relapse and non-relapse are analyzed, and the expression conditions of various immune cells in a whole blood sample after interferon treatment achieves functional cure are observed. Through the research results, the chronic hepatitis B interferon antiviral treatment is guided, a new immune target is provided for exploring chronic hepatitis B antiviral treatment, the cure rate is improved, and the recurrence rate is reduced.
According to research, the invention discovers that the distribution situation and dynamic change of peripheral blood T lymphocytes after the Peg-IFN combined TDF is clinically cured can be obviously seen through experimental results and clinical data analysis, wherein the total proportion of CD4+ T cells and Treg cells is in a descending trend, the total proportion of CD8+ T cells is not obviously changed, and the change of the CD4+ T cells, the Treg cells and the CD4/CD8 ratio can be used for monitoring and predicting the curative effect of the Peg-IFN alpha-2 b combined tenofovir in anti-HBV treatment; CXCR5 plays an important role in clinical healing and relapse after Peg-IFN and tenofovir are combined in anti-HBV treatment, the total occupation ratio of Tfh and Tfc is higher in both the Cure group and the Re group, and the total occupation ratio of the Tfh and the Tfc is lower in both the CL group and the HC group, so that when surface antigen clearance is achieved, both Tfh and Tfc are maintained at a higher concentration, and the rapid decline of the Tfh and the Tfc is probably used for indicating HBsAg reviving, and the occupation ratio is maintained to be high, so that HBsAg clearance is facilitated and clinical functional healing is achieved.
Drawings
Figure 1 is a graph of flow analysis of CD3, CD4, CD8 and Treg cells in PBMCs.
FIG. 2 shows the distribution of CD4+ T cells in each group.
FIG. 3 is the distribution of CD8+ T cells in each group.
FIG. 4 is the distribution of the ratio of CD4+ T cells to CD8+ T cells in each group.
Figure 5 is the distribution of Treg cells in each group.
Fig. 6 is a flow analysis diagram of Tfh cells and Tfc cells in PMBC.
Figure 7 is the distribution of CXCR5+ CD4+ T cells among the groups.
Figure 8 is the distribution of CXCR5+ CD8+ T cells among the groups.
Detailed Description
The invention is further illustrated by the following examples, which are not intended to be limiting.
The experimental methods in the following examples are all conventional methods unless otherwise specified; the reagents used are, unless otherwise specified, conventional in the art and are commercially available.
Example 1
1 materials and methods
1.1 study subjects
As subjects, 35 CHB patients were included who were admitted to the department of the college of chongqing medicine from 2019.10 to 2021.10.
Inclusion criteria were: (1) adult (age > 18 years) patients with chronic hepatitis B, but less than 60 years of age; (2) agree to treatment with Peg-IFN α -2b in combination with Tenofovir (TDF) and can adhere to an out-patient follow-up; (3) the study and treatment risks were known and informed consent was signed.
Exclusion criteria: (1) combined with other viral infections, such as hepatitis A, hepatitis C, hepatitis E, HIV infection, etc.; (2) contraindications for IFN therapy: such as severe infection, schizophrenia, severe end-stage liver disease, pregnant women, etc.; (3) combined with severe chronic diseases, such as coronary heart disease, alcoholic liver disease, end-stage renal disease, severe lupus erythematosus and the like; (4) some severe adverse reactions occurred with Peg-IFN α -2b in combination with TDF.
Stopping the medicine standard: normal liver function; HBsAg is less than 0.04IU/mL (can not be detected); HBV DNA is less than 100IU/mL.
Recording personal information and clinical information of the patients who enter the group, wherein the personal information and the clinical information comprise age, sex, treatment period and the like; the follow-up condition of the patient during the treatment period comprises indexes of blood routine, liver function, hepatitis B, HBV DNA content, AFP and the like. The study has been approved by the ethical committee of the first hospital affiliated with the university of Chongqing medical sciences (2020-409).
1.2 Experimental reagents and instruments
1.2.1 Main Experimental reagents
1.2.2 Main laboratory instruments and Equipment
1.3 Experimental methods
1.3.1 specimen Collection
Peripheral blood of 10ml was collected from healthy volunteers and patients enrolled in the study at an outpatient clinic and collected using vacuum blood collection tubes. And specimen processing was performed within two hours.
1.3.2PBMC extraction
(1) 1200r/min 10min centrifugal blood sample
(2) Aspirate 1ml serum into a 1.5ml EP tube
(3) Adding the residual plasma into a 15ml centrifuge tube containing 4ml of PBS, and mixing uniformly
(4) Slowly add 4ml of the solution (45 ℃ inclined slow add)
(5) Placing into centrifuge 400G 40min, slowly ascending and slowly descending
(6) The serum is put into a centrifuge 12000r 10min for centrifugation and then sucked into a new EP tube
(7) Sucking the suspended PBMC in the centrifuge tube by capillary tube
(8) Putting into a centrifuge for 300G 8min for centrifugation
(9) Sucking out the upper liquid
(10) Cell counting
(11) Centrifuging in a centrifuge at 300G 5min
(12) Sucking out the supernatant liquid
(13) Adding RPMI1640 (800 ul or 1.2 ml) into the centrifuge tube
(14) Slowly dropwise adding equivalent cell freezing solution
(15) Mixing, separating to 1.5ml freezing tube (2 tube or three tubes)
(16) After gradient freezing, putting the freezing tube into liquid nitrogen for preservation
1.3.3 cell Resuscitation
(1) Preparation of RPMI1640+10% FBS about 5ml as the culture Medium
(2) Taking the PBMC out of the liquid nitrogen tank, putting the PBMC into a water bath kettle at 37 ℃, and transferring the PBMC into a culture medium when ice cubes are dissolved almost;
(3) Centrifuging: 300g,5min, room temperature, discarding the supernatant;
(4) Counting with PBS, sucking 20ul PBMC, placing into a cell counter, and ensuring the number not less than 2 × 10 under a mirror 6 ；
(5) Centrifuging: 300g,5min, room temperature, discard the supernatant and divide them into three tubes 50. Mu.l. Times.3 tubes, tube1 blank tube, tube2 sample tube, tube3 isotype control.
1.3.4 flow cytometry analysis of Peripheral Blood Mononuclear Cells (PBMC)
(1) Fc blocking: adding 2.5 μ l of blocking agent into 50 μ l of cell system, keeping away from light for 8min, and washing-free;
(2) Antibodies were added to each tube:
tube1 (blank): is free of
Tube2 (sample Tube):
PE MouseAnti-Human CD3：0.5μl
FITC MouseAnti-Human CD8：2μl
PerCP-Cy5.5 MouseAnti-Human CD4：1μl
BV650 MouseAnti-Human CD25：1μl
BV421 Rat Anti-Human CXCR5(CD185)：0.5μl
Alexa
647Mouse Anti-Human CD127：2μl
tube3 (isotype control):
PE Mouse Anti-Human CD3：0.5μl
FITC Mouse Anti-Human CD8：2μl
PerCP-Cy5.5 Mouse Anti-Human CD4：1μl
BV650 Mouse IgG1,κIsotype Control：0.5μl
Alexa
647Mouse IgG1,κIsotype Control：0.5μl
BV421 Mouse IgG2b,κIsotype Control：0.5ul
(3) After adding 1ml PBS, the mixture is kept still for 20min in dark.
(4) Centrifuging: 300g,5min, room temperature, discarding the supernatant;
(5) Adding 400ul PBS again, 300g at room temperature, and centrifuging for 5min for re-suspension;
(6) Moving into a flow tube through a filter membrane;
(7) Preparing a single male pipe: using a BD TM CompBeads Anti-Mouse Ig, kappa and BD TM CompBeads
The Negative Control 1 was mixed into 6 tubes, 50ul each, and added to PE Mouseanti-Human CD3, FITC Mouseanti-Human CD8, perCP-Cy5.5 Mouseanti-Human CD4, BV650 Mouse IgG1,. Kappa.Isotype Control, alexa
647Mouse IgG1,. Kappa.Isotype Control,. BV421 Mouse IgG2b,. Kappa.Isotype Control.
(6) Repeating the operations in (3) and (6);
(7) Debugging the instrument and detecting on the computer.
(8) Data analysis was performed by FlowJo.
1.4 statistical analysis
Mapping and analysis were performed using GraphPadPrism 8.0. In the measurement data, adopting t test to meet the normality and the homogeneity of variance; the variance is irregular and a Welch's correction t test is adopted; the normality was not satisfied using the Mann-Whitney rank sum test. The counting data were examined precisely by Fisher's. When P is less than 0.05, the difference between groups has statistical significance.
2 results
2.1 the distribution and dynamic changes of T lymphocytes in peripheral blood after clinical cure are obvious by combining Peg-IFN with TDF to resist HBV
We performed some grouping of PBMCs: the health control group (HC, n = 10), the HBsAg Clearance group (clear group, CL, n = 10), the Cure group (Cure, n = 10), the relapse group (Recrudescence, RE, n = 15), the health control group is a sample of a Healthy population in which HBsAg is negative and HBsAb is positive, the HBsAg Clearance group is a sample of a patient who has reached HBsAg negative by the first detection after the therapy of Peg-IFN in combination with TDF, the Cure group is a sample of a patient in which HBsAg becomes negative and remains for half a year or more after the therapy of Peg-IFN in combination with TDF, and the relapse group is a sample of a patient in which HBsAg becomes negative after the therapy of Peg-IFN in combination with TDF and has returned to positive after the follow-up visit. Flow analysis was performed on CD3, CD4, CD8 and Treg cells in their PMBC (fig. 1).
2.1.1CD4+T cell distribution
The percentage of CD4+ T cells to T cells (abbreviated as CD4+ T total) was statistically significant between Re and HC, and between Re and CL, with HC higher than Re (P = 0.0029), CL higher than Re (P < 0.001), and the difference between Re and curr not statistically significant (P > 0.05), as shown in fig. 2.
2.1.2CD8T cell distribution
Percentage of CD8+ T cells to T cells (abbreviated as CD8+ T total) in flow analysis, the differences between Re and HC, re and Cure, and Re and CL were not statistically significant (P > 0.05), as shown in fig. 3.
Ratio of 2.1.3CD4+ T cells to CD8+ T cells
The ratio of CD4+ T cells to CD8+ T cells (abbreviated CD4/CD8 ratio) was statistically significant between the Re and CL groups, with the CL group being higher than the Re group (P = 0.010) and the differences between the Re and HC, re and Cure groups being statistically insignificant (P > 0.05), see fig. 4.
2.1.4Treg cell distribution
The proportion of Treg cells in T cells (abbreviated as Treg proportion) was statistically significant between the Re group and the CL group, the Re group and the HC group, the CL group was higher than the Re group (P = 0.003), the HC group was higher than the Re group (P = 0.03), and the difference between the Re group and the Cure group was not statistically significant (P > 0.05), as shown in fig. 5.
In conclusion, it can be found that the distribution of CD4+ and Treg cells of PBMC of peripheral blood after hepatitis B surface antigen clearance, clinical cure and relapse of patients treated with the combination of Peg-IFN alpha-2 b and TDF for CHB is obviously different. Similarly, the dynamic changes of the immune cells have a certain correlation with the curative effect of the Peg-IFN alpha-2 b, wherein the change of the CD4+ T cells is most obvious, and the CD4+ T cells all show a descending trend from the hepatitis B surface antigen clearance period to clinical cure or relapse, compared with the non-obvious change trend of the CD8+ T cells; the CD4/CD8 ratio is different between the CL group and the Re group and between the CL group and the Cure group, the CD4/CD8 ratio from the CL stage to the Re stage shows a descending trend, and the CD4/CD8 ratio from the CL stage to the Cure stage is not obviously different. Changes in CD4+ T cells, treg cells and CD4/CD8 ratio can be used to predict or monitor the efficacy of Peg-IFN α -2b in combination with TDF.
2.2CXCR5 plays an important role in the process of relapse after the clinical cure by the combination of Peg-IFN alpha-2 b and TDF anti-HBV treatment
Similarly, we performed flow analysis of two subsets of CXCR5 follicular helper T cells (CXCR 5+ CD4+ T cells) and follicular cytotoxic T cells (CXCR 5+ CD8+ T cells) (fig. 6) to investigate the differences between HBsAg Cleared (CL), cured (Cure), relapsed (Re) and Healthy Control (HC).
2.2.1CXCR5+ CD4+ T cell distribution
The proportion of CXCR5+ CD4+ T in T cells (abbreviated as TFH proportion) was statistically different between the Re group and the CL group (P < 0.001), the Re group and the HC group, and the Re group and the Cure group, with the CL group higher than the Re group (P = 0.0097), the HC group higher than the Re group (P = 0.031), as shown in fig. 7.
2.2.2CXCR5+ CD8+ T cell distribution
The ratio of CXCR5+ CD8+ T in T cells (abbreviated as TFC ratio) was statistically different between Re and CL groups, higher than Re (P = 0.0006), HC higher than Re (P = 0.0021), and Re higher than Re (P = 0.023), as well as between Re and Cure, as shown in fig. 8.
Flow experiment results show that the distribution of TFH cells and TFC cells of patients treated by Peg-IFN alpha-2 b and TDF with CHB is obviously different after hepatitis B surface antigen clearance, clinical cure and relapse. During the period from hepatitis B surface antigen clearance to clinical cure or relapse, both TFH cells and TFC cells present a descending trend, during the initial stage of hepatitis B surface antigen clearance, TFH cells and TFC cells of peripheral blood of a patient are in a high-expression state higher than that of a healthy group, and after the patient achieves functional cure along with the advancement of treatment process, both Tfh cells and Tfc cells present a descending trend lower than that of the healthy group, while in a relapse group, tfh cells and Tfc cells of the patient present an expression trend lower than that of the cure group, so that the depletion of the Tfh cells and the Tfc cells is closely related to the curative effect of Peg-IFN alpha-2 b combined TDF, and the anti-HBV curative effect of Peg-IFN alpha-2 b combined treatment or new immune targets are predicted through the detection of such subcellular populations to reduce the relapse rate and improve the cure rate.
3 analysis and conclusion
Our study found that: while the overall proportion of CD4+ T cells in both the Cure and Re groups was lower than that in the HC and CL groups, our previous studies found that the overall proportion of CD4+ T cells in CHB patients was higher than that in the HC group and that of CD8+ T cells was lower than that in the HC group, and that T cell dysfunction and failure in the Cure and Re groups was restored compared to CHB patients by the CD4/CD8 ratio, CD8+ T cells are characterized by clearance of aberrant factors or resistance to invasion by foreign factors through massive expansion and differentiation into cytotoxic effector cells. Depletion of CD8+ T cells is associated with a progressive impairment of their function, especially in terms of expansion capacity, secretion of cytokines and elimination of antigens. We have collected clinical data showing that both the HBV-DNA of the Cure group and the Re group are below the lower detection limit compared to CHB patients, although the HBV-DNA of the Re group is increased with the lapse of time; in the distribution of Treg cells, the Re group is obviously lower than the HC group and the CL group, the Treg cells are a subgroup of CD4+ T cells, have the functions of immune negative regulation, can inhibit the auxiliary effect of the CD4+ T cells on the CD8+ T cells, and can nonspecifically inhibit the activation and proliferation of the CD4+ T cells and the CD8+ T cells by secreting suppressive cytokines. Treg cells are more active in the Re group than in the Cure group, which can reflect by negative feedback mechanism that clearance of the Re group for HBsAg is weaker than that of the Cure group. Therefore, for the curative effect of realizing whether the functional cure is relapsed, the Treg cells and the CD8+ T cells are good monitoring indexes, and meanwhile, the detection of other indexes such as HBV DNA, AST, ALT and the like also needs to be analyzed together, and the curative effect can be better predicted only by controlling the dynamic change of each index.
Two subsets, follicle helper T cells (Tfh, CXCR5+ CD4+ T cells), follicle cytotoxic T cells (Tfc, CXCR5+ CD8+ T cells), have received increasing attention and emphasis from experts in the treatment of CHB in recent years. Their marker surface molecule CXCR5 and its ligand CXCL13 have also been included in extensive research.
The concordant role of the Tfh cell subpopulation in humoral immunity for adaptive immune responses, as well as the accessory role of the production of various classes of antibodies, is the direction of our major research. Mature Tfh cells are located in follicles of Secondary Lymphoid Organs (SLOs), and differentiate into memory B cells and plasma cells by assisting activation of B cells located therein in the Germinal Center (GC) and generate corresponding mature antibodies. Moreover, tfh cells play very important roles and roles in cancer control, antimicrobial pathogen infection, and prevention of autoimmune hyperactivity as a reservoir for HIV. Of course, the Tfh cell subpopulation is no exception in anti-HBV. In the present study, it was found that the Tfh total occupancy was lower in both the Re and Cure groups than in the CL and HC groups, and that the Re group was also lower than the Cure group. This indicates that the Tfh total ratio is directly related to HBsAg clearance and has good immunological value for predicting the efficacy of treatment with Peg-IFN-alpha in combination with TDF.
CXCR5+ CD8+ T cells, a special CD8+ subset, are a subset of cells that have been discovered in recent years and are included in research. Im Se Jin et al performed detailed characteristic study on the cells of this subgroup at the transcriptome level, and found that the subgroup is an adaptive response to the exhausted PD-1+ CD8+ T cells. Has similar stem cell characteristics during chronic infection of chronic hepatitis B, namely self-renewal and differentiation into terminal CXCR5+ CD8+ T cells to exert antiviral efficacy. The transcription factor TCF1 is crucial for the generation of this subpopulation, whereas the blockade of PD-1 can cause a sharp expansion and differentiation of this subpopulation towards terminal stages. CXCR5+ CD8+ T cells play a key role in controlling viral replication, these CXCR5+ CD8+ T cells, which are affected by CXCL13 chemotaxis, migrate into B cell follicles have fewer inhibitory receptors and exhibit greater cytotoxicity than a subset of CXCR 5-; also shown is greater therapeutic potential in HIV. The research shows that TFC total ratio is lower than that of a CL group and a HC group in both Re and Cure groups, and that the Re group is also lower than that of the Cure group, so that TFC cells show better antiviral efficacy in the initial stage of CL, while in the Re group, HBsAg relapse occurs due to exhaustion of CD8+ T cells, while in the Cure group, tfc total ratio is higher than that of the Re group, so that Tfc plays a critical role in controlling replication of HBV viruses, and CXC5+ CD8+ T cells can serve as a breakthrough point for improving Cure rate and reducing relapse rate of anti-HBV treatment.
In conclusion, the invention can show that the distribution and dynamic change of peripheral blood T lymphocytes are obvious after the Peg-IFN and TDF are combined to achieve clinical cure by anti-HBV through experimental results and clinical data analysis, wherein the total proportion of CD4+ T cells and Treg cells is in a descending trend, the total proportion of CD8+ T cells is not obviously changed, and the change of the ratio of CD4+ T cells, treg cells and CD4/CD8 can be used for monitoring and predicting the curative effect of Peg-IFN alpha-2 b and tenofovir in anti-HBV treatment.
CXCR5 plays an important role in clinical healing and relapse processes after anti-HBV treatment is achieved through Peg-IFN alpha-2 b and tenofovir. The total occupancy of Tfh and Tfc is higher in both the Cure group and the Re group than in the CL and HC groups, so that Tfh and Tfc are maintained at a higher concentration when surface antigen clearance is achieved, and their rapid decline is likely to indicate a return to positive HBsAg, which is more favorable to clearance of HBsAg and to achieve a clinically functional Cure. CXCR5/CXCR13 is expected to become a new immune target for achieving functional cure.
Claims (10)
- Use of t cells as biomarkers for the manufacture of a product for monitoring or predicting the efficacy of anti-HBV therapy, characterized in that: the T cells comprise Treg cells, CD4+ T cells and CD8+ T cells.
- 2. Use according to claim 1, characterized in that: using the changes in CD4+ T cell content, treg cell content and CD4/CD8 ratio to predict or monitor the efficacy of anti-HBV treatment; compared with a reference, the content of CD4+ T cells of the subject is remarkably reduced, the CD4/CD8 ratio shows a remarkably reduced trend, the content of Treg cells is remarkably reduced, and the medicine has a curative effect, and vice versa; preferably, the reference is the normal population and/or the cell content of the subject prior to administration.
- Use of t cells as biomarkers for the preparation of a product for predicting risk of relapse after clinical functional cure achieved in anti-HBV therapy, characterized by: the T cells include CD8+ subset CXCR5+ CD8+ T cells and CD4+ subset CXCR5+ CD4+ T cells.
- 4. Use according to claim 3, characterized in that: a significant decrease in CXCR5+ CD8+ T cells and CXCR5+ CD4+ T cells in the subject compared to the control of the non-relapsed group is indicative of a high risk of HBsAg relapse, whereas a high level of occupancy of CXCR5+ CD8+ T cells and CXCR5+ CD4+ T cells in T cells is indicative of no or low risk of relapse.
- 5. Use of a substance that detects the amount of Treg cells, CD4+ T cells, CD8+ T cells in the manufacture of a product for monitoring or predicting the efficacy of an anti-HBV treatment.
- 6. Use according to claim 5, characterized in that: using the changes in CD4+ T cell content, treg cell content and CD4/CD8 ratio to predict or monitor the efficacy of anti-HBV treatment; compared with the reference, the content of CD4+ T cells of the subject is obviously reduced, the CD4/CD8 ratio shows a trend of obviously reducing, the content of Treg cells is obviously reduced, and the medicine has the curative effect, and vice versa.
- 7. Use of a substance that detects the amount of CD8+ subpopulations CXCR5+ CD8+ T cells and CD4+ subpopulations CXCR5+ CD4+ T cells in the manufacture of a product for predicting the risk of recurrence following clinical functional healing in anti-HBV treatment.
- 8. Use according to claim 7, characterized in that: a significant decrease in CXCR5+ CD8+ T cells and CXCR5+ CD4+ T cells in the subject compared to the control of the non-relapsed group is indicative of a high risk of HBsAg relapse, whereas a high level of occupancy of CXCR5+ CD8+ T cells and CXCR5+ CD4+ T cells in T cells is indicative of no or low risk of relapse.
- 9. Use according to any one of claims 1 to 8, characterized in that: the T cells refer to T cells in peripheral blood; the anti-HBV treatment is Peg-IFN treatment, preferably combination treatment of Peg-IFN and tenofovir.
- 10. Use according to any one of claims 5 to 8, characterized in that: the substance is selected from antibody and chip.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210842043.9A CN115166250A (en) | 2022-07-18 | 2022-07-18 | Use of T cells as biomarkers for monitoring or predicting the efficacy of anti-HBV treatment or predicting the risk of relapse |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210842043.9A CN115166250A (en) | 2022-07-18 | 2022-07-18 | Use of T cells as biomarkers for monitoring or predicting the efficacy of anti-HBV treatment or predicting the risk of relapse |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115166250A true CN115166250A (en) | 2022-10-11 |
Family
ID=83494499
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210842043.9A Pending CN115166250A (en) | 2022-07-18 | 2022-07-18 | Use of T cells as biomarkers for monitoring or predicting the efficacy of anti-HBV treatment or predicting the risk of relapse |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115166250A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115040538A (en) * | 2022-05-23 | 2022-09-13 | 重庆医科大学 | Application of human CXCR5+ CD8+ T cell in preparing medicine for treating chronic hepatitis B |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20160272707A1 (en) * | 2013-09-11 | 2016-09-22 | Compugen Ltd. | Vstm5 antibodies, and uses thereof for treatment of cancer, infectious diseases and immune related diseases |
| CN106581672A (en) * | 2015-10-15 | 2017-04-26 | 广东思峰生物科技有限责任公司 | RhIL-12 containing medicine composition for treating non-active hepatitis B |
| WO2018204764A1 (en) * | 2017-05-05 | 2018-11-08 | Camp4 Therapeutics Corporation | Identification and targeted modulation of gene signaling networks |
| US20200246467A1 (en) * | 2019-02-06 | 2020-08-06 | Synthorx, Inc. | Il-2 conjugates and methods of use thereof |
-
2022
- 2022-07-18 CN CN202210842043.9A patent/CN115166250A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20160272707A1 (en) * | 2013-09-11 | 2016-09-22 | Compugen Ltd. | Vstm5 antibodies, and uses thereof for treatment of cancer, infectious diseases and immune related diseases |
| CN106581672A (en) * | 2015-10-15 | 2017-04-26 | 广东思峰生物科技有限责任公司 | RhIL-12 containing medicine composition for treating non-active hepatitis B |
| WO2018204764A1 (en) * | 2017-05-05 | 2018-11-08 | Camp4 Therapeutics Corporation | Identification and targeted modulation of gene signaling networks |
| US20200246467A1 (en) * | 2019-02-06 | 2020-08-06 | Synthorx, Inc. | Il-2 conjugates and methods of use thereof |
Non-Patent Citations (3)
| Title |
|---|
| X PANG 等: "Combination of pegylated interferon-alpha and nucleos(t)ide analogue treatment enhances the activity of natural killer cells in nucleos(t)ide analogue experienced chronic hepatitis B patients", CLINICAL AND EXPERIMENTAL IMMUNOLOGY, vol. 202, no. 1, 31 October 2020 (2020-10-31), pages 80 * |
| 王嘉悦: "聚乙二醇干扰素治疗慢乙肝实现功能性治愈的临床及免疫学特征研究", 《中国优秀硕士学位论文全文数据库 医药卫⽣科技辑》, 15 March 2022 (2022-03-15), pages 1 - 463 * |
| 郭志勇;贺文娟;裴军芳;: "聚乙二醇干扰素α-2a注射液联合替诺福韦酯治疗e抗原阳性慢性乙型肝炎疗效分析", 中国药物与临床, no. 22, 25 November 2019 (2019-11-25), pages 118 - 120 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115040538A (en) * | 2022-05-23 | 2022-09-13 | 重庆医科大学 | Application of human CXCR5+ CD8+ T cell in preparing medicine for treating chronic hepatitis B |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Livanos et al. | Intestinal host response to SARS-CoV-2 infection and COVID-19 outcomes in patients with gastrointestinal symptoms | |
| Romero et al. | Interferon (IFN)–γ–inducible protein–10: association with histological results, viral kinetics, and outcome during treatment with pegylated IFN-α2a and ribavirin for chronic hepatitis C virus infection | |
| Rubio et al. | Early posttransplantation donor-derived invariant natural killer T-cell recovery predicts the occurrence of acute graft-versus-host disease and overall survival | |
| Daichou et al. | Characteristic cytokine products of Th1 and Th2 cells in hemodialysis patients | |
| Chang et al. | Hepatitis B flare in hepatitis B e antigen-negative patients: a complicated cascade of innate and adaptive immune responses | |
| CN111454903B (en) | Immune cell in vitro culture, induction, activation and cryopreservation method and cell bank establishment thereof | |
| Tavakolpour et al. | Pathogenic and protective roles of cytokines in pemphigus: a systematic review | |
| Brandt | Adhesiveness to glass and phagocytic activity of neutrophilic leukocytes in myeloproliferative diseases | |
| Kas-Deelen et al. | Uninfected and cytomegalic endothelial cells in blood during cytomegalovirus infection: effect of acute rejection | |
| CN109568585B (en) | Application of CD38 inhibitor in preparation of anti-rheumatoid arthritis medicine | |
| Liang et al. | Correlations of disease severity and age with hematology parameter variations in patients with COVID‐19 pre‐and post‐treatment | |
| CN115166250A (en) | Use of T cells as biomarkers for monitoring or predicting the efficacy of anti-HBV treatment or predicting the risk of relapse | |
| Wiberg et al. | Profound but transient changes in the inflammatory milieu of the blood during autologous hematopoietic stem cell transplantation | |
| Ribeiro et al. | Cytokines profile in patients with acute and chronic hepatitis B infection | |
| Ciccocioppo et al. | The immune modulatory effects of umbilical cord-derived mesenchymal stromal cells in severe COVID-19 pneumonia | |
| Guo et al. | Obesity is associated with attenuated tissue immunity in COVID-19 | |
| Ruiz-Moreno et al. | Levamisole and interferon in children with chronic hepatitis B | |
| Wang et al. | Serum IL-5 levels predict HBsAg seroclearance in patients treated with Nucleos (t) ide analogues combined with pegylated interferon | |
| Pinto et al. | Genes Related to Antiviral Activity, Cell Migration, and Lysis Are Differentially Expressed in CD4+ T Cells in Human T Cell Leukemia Virus Type 1-Associated Myelopathy/Tropical Spastic Paraparesis Patients | |
| Müller et al. | Impaired lipopolysaccharide-inducible tumor necrosis factor productionin vitroby peripheral blood monocytes of patients with viral hepatitis | |
| CN111184742B (en) | Application of TREM-2+ T cells in preparation of drugs for treating tuberculosis | |
| CN112300992B (en) | NK cell culture solution and multistage activated NK cell culture method | |
| Lu et al. | Entecavir up-regulates dendritic cell function in patients with chronic hepatitis B | |
| Lin et al. | Dynamic changes of the proportion of HLA-DR and CD38 coexpression subsets on T lymphocytes during IFN-based chronic hepatitis B treatment | |
| CN114366758A (en) | Application of CD146+ mesenchymal stem cell subset in preparation of medicine for preventing and treating premature ovarian failure |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |