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*Only for medical professionals to read for reference.
Wonderful continue! The European Union Against Rheumatism (EULAR) conference in 2021 will be held online, and rheumatology immunologists and doctors around the world will enjoy this academic feast
.
The "Medical Channel of Rheumatology and Kidney Disease" and a group of authoritative experts from Peking University People's Hospital will provide timely conference reports for everyone, and grasp the latest and hottest international frontier developments in the field of rheumatology immunology for the first time
.
01Professor Kristina Lejon from the University of Umeå in Sweden gave the title of “Decreased Levels of T Follicular Helper (CD4+CXCR5+) Cells and CD27+CD38+and CD27+CD38- B Cells in Ankylosing Spondylitis Patients Correlate with Marker of Inflammation" report, introduced the study of the correlation between CD4+CXCR5+ Tfh cells, CD27+CD38+ and CD27+CD38- B cells and the inflammatory state of patients with ankylosing spondylitis (AS)
.
By performing flow cytometry on CD4+CXCR5+ Tfh cells and CD27+CD38+ and CD27+CD38- B cells in the peripheral blood of AS patients with different genders and healthy controls, they found that these three groups of cells in AS patients were significantly reduced compared with healthy controls, and Observed in female patients, there is a significant correlation with the Bath AS Measurement Index (BASMI), which may be involved in the pathogenesis of AS
.
Figure 1: Tfh cell reduction in AS patients Figure 2: Abnormal B cell differentiation in AS patients Dr.
Viviana Marzaioli from University College Dublin, National University of Ireland, brought the title "CD209+/CD14+Dendritic Cells are enriched and activated at the site of inflammation and are modulated "by JAK/STAT signalling" report, introduced the pathogenic role of CD209+/CD14+ DC cells in inflammatory arthritis (IA)
.
Taking rheumatoid arthritis (RA) and psoriatic arthritis (PsA) and other IA peripheral blood and joint synovium as the research object, they found that there are CD209+/CD14+ DC cell subsets in the peripheral blood of patients with active IA, and This group of cells can infiltrate the joints of patients with RA and PsA
.
Further research found that JAK/STAT inhibitors can target this group of pathogenic DC cells, while tumor necrosis factor (TNF) inhibitors are ineffective
.
Figure 3: Overactivation of CD209+/CD14+ DC cell subsets in the peripheral blood of IA patients Figure 4: JAK/STAT inhibitors target to inhibit pathogenic CD209+/CD14+ DC cell subsets brought by Dr.
Megan Hanlon from the University College of Dublin, National University of Ireland The report titled "CD206+CD163+pathogenic macrophages enriched in Rheumatoid Arthritis synovial tissue with distinct transcriptional signatures" introduced the role and mechanism of CD206+CD163+ macrophages in the pathogenesis of RA
.
Studies have found that CD206+CD163+ macrophages are the main group of macrophages in the synovial tissues of normal people and RA patients
.
In the RA state, this group of cells is significantly enriched in synovial tissues, highly expressing CD40, and is positively correlated with DAS28
.
RNA-seq results show that the gene expression profile of CD206+CD163+ macrophages in RA synovial tissue is significantly different from that of CD206-CD163-macrophages, and is significantly different from peripheral blood M1 and M2 cells, showing a unique transcriptome Features
.
The results of metabonomic analysis also showed that CD206+CD163+ macrophages are a unique group of macrophages with a characteristic metabolic phenotype
.
Functional studies have further found that CD206+CD163+ macrophages express a variety of inflammatory factors and play an important role in the inflammatory lesions of RA synovial tissue
.
Figure 5: The role and mechanism of CD206+CD163+ macrophages in the pathogenesis of RA 02 Immune Molecules Dr.
Eric Malmhall-Bah from the University of Gothenburg in Sweden brought a report titled "Rho expression facilitates T cell migration to lymph nodes in response inflammation", The role of GGTase-I deficient macrophages in activating Rho protein-dependent CD4+ T cell migration in the pathogenesis of arthritis is introduced
.
They constructed macrophage GGTase-I conditional knockout mice (GLC mice).
Studies have suggested that GLC mice will exhibit excessive activation of Rho protein and erosive arthritis similar to RA
.
They further researched and found that T cells play an important role in arthritis in GLC mice, CD4+ T cells in GLC mice exhibit unique characteristics, and Rho protein in macrophages can affect CD4+ T cells in GLC mice
.
In addition, the use of CTLA4-FP to interfere with the interaction between macrophages and T cells will reduce T cell activation in GLC mice and the inflammatory phenotype of mice
.
Figure 6: GLC mouse CD4+ T cells exhibit unique immunological characteristics.
Professor Maria I Bokarewa from the University of Gothenburg in Sweden brought a report entitled "IGF1R dependent cell interaction and regulation of autoantibody production in rheumatoid arthritis", introducing insulin-like growth The study of the key role of factor 1 receptor (IGF1R) signaling in cell communication and antibody production
.
They found that inhibition of IGF1R would lead to the expansion of CD21+ antigen-presenting cells and a significant reduction in the expression of ICOSL; inhibition of IGF1R would also lead to the expansion of the marginal zone and the aggregation of IgM+CD21+ B cells in the marginal zone; in addition, inhibition of IGF1R It can also lead to the production of a variety of autoantibodies such as anti-CCP, RF, and anti-DNA
.
Figure 7: Inhibition of IGF1R leads to the accumulation of IgM+CD21+ B cells in the marginal zone.
Figure 8: Inhibition of IGF1R leads to the production of autoantibodies.
03 New immunomodulatory drugs Dr.
Jyothsna Visweswaraiah of Merck, USA brought the title "Generation of PT101, a highly The report "selective IL-2 mutein for treatment of autoimmune diseases" introduced the application research of a highly selective mutant IL-2—PT101 in the treatment of autoimmune diseases
.
PT101 was developed by replacing asparagine at position 88 of IL-2 to reduce its affinity with IL-2Rβ, and then through structural modification to increase its affinity with IL-2Rα, and then endow it with the characteristics of a drug
.
Studies have shown that PT101 can selectively increase Treg cells without affecting NK cells
.
In vitro experiments in humans and rhesus monkeys have shown that PT101 can selectively increase Treg in a dose-dependent manner; experiments in healthy volunteers have also shown that PT101 can increase total Treg and CD25bright Treg without affecting NK cells and Pro-inflammatory T cells
.
These findings suggest that PT101 can be considered as a treatment option for autoimmune diseases such as SLE
.
Figure 9: Construction of highly selective mutant IL-2--PT101 Figure 10: Compared with wild-type IL-2, PT101 selectively activates human and rhesus monkey Treg cells in vitro.
Dr.
Ivan Zvyagin of the University brought a report titled "AS-related TCR beta clonotypes are present in different inflamed tissues of patients with spondyloarthropathies", introducing different types of spondyloarthritis (SpA) patients with different tissue ankylosing spondylitis (AS) Related TCR beta clonotype research
.
They treated a variety of SpA (including AS, PsA, juvenile idiopathic arthritis) and combined extra-articular manifestations (ulcerative colitis, Crohn’s disease and uveitis) patients with peripheral blood, joint fluid, intestinal tissue and Conjunctival swabs were subjected to TCR sequencing, and HLA-B27 typing was tested
.
The results showed that the AS-related bTCR clonotypes that have been found so far are widespread in the synovial fluid of different types of SpA patients, and there is a strong correlation with the genotype of HLA-B27
.
Interestingly, AS-related bTCR clones can also be detected in other sites of inflammation in patients with SpA with extra-articular manifestations, such as the small intestine of patients with IBD and the conjunctiva of patients with uveitis
.
Figure 11: AS-related bTCR clonotypes are commonly found in the synovial fluid of different types of SpA patients.
Figure 12: AS-related bTCR clones can also be detected in other inflammation sites of SpA patients with extra-articular manifestations.
Hu Fanlei commented on rheumatism Immune disease is an autoimmune disease with a complex pathogenesis, which not only includes a large number of activation of natural immune response, but also involves excessive activation of adaptive immune response
.
Innate immune cells such as monocytes/macrophages, dendritic cells, mast cells, natural killer cells, and adaptive immune cells such as T cells and B cells all play an important role in the pathogenesis of rheumatism
.
In addition to the classic subpopulations, the identification of new immune cell subpopulations is a major trend in immunological research at present, which will provide new clues for the in-depth understanding of the pathogenesis of rheumatism and immunotherapy strategies; and the tissue-specific new immune system Cell research will further provide help for the immunological diagnosis and treatment of organ-specific rheumatic immune diseases
.
The breaking of immune homeostasis and the activation of autoimmunity are the key and initiating link of the onset of rheumatoid immune diseases.
Immune balance therapy is one of the fundamental ways to achieve the remission of rheumatoid immune diseases
.
Research conducted by the Rheumatology Team of Peking University People's Hospital and several teams at home and abroad led by Professor Li Zhanguo has shown that low-dose IL-2 has great advantages in restoring immune balance and treating rheumatism, especially SLE, and has been clinically applied
.
Further transformation and upgrading of the drug to improve its efficacy and stability will have important clinical significance and application prospects
.
Some studies have shown that TCR and BCR of rheumatoid diseases such as RA and SLE exhibit unique variable region characteristics and present some dominant sequences
.
With the maturity and improvement of immune repertoire technology, the systematic analysis of TCR and BCR repertoire of rheumatoid immune diseases and identification of their dominant sequences will have important theoretical guiding significance for the development of antibody drugs and the design of therapeutic TCR/BCR peptide vaccines.
And application value
.
Expert profile Hu Fanlei, Department of Rheumatology and Immunology, Peking University People’s Hospital/Beijing Key Laboratory of Rheumatology, Associate Researcher, Doctoral Supervisor, Deputy Secretary-General of the Clinical Immunization Branch of the Chinese Society of Immunology, Youth Committee ENDOCR METAB IMMUNE Magazine Section Editor, Frontiers in Immunology, Experimental and The editorial board member of Therapeutic Medicine, Beijing Science and Technology Rising Star China Immunology Academic Award-Young Scholar Award winner, has long been engaged in research on the pathogenesis of autoimmune diseases (especially rheumatoid arthritis) and immunological diagnosis and treatment, and has achieved a series of innovative results for nearly 5 years.
The first/corresponding author has published 22 SCI papers, including Nature Communications, Annals of the Rheumatic Diseases, Journal of Autoimmunity, Journal of Immunology, European Journal of Immunology, etc.
Undertake the National Natural Science and Youth Project, Beijing Science and Technology New Star Project, etc.
More than 10 projects; jointly undertake 1 project of the National Natural Science Research Plan.
Obtained (please) 6 national invention patents.
Received multiple scientific research awards, including the first prize of the University Science and Technology Progress Award, the second prize of the Chinese Medical Science and Technology Award, etc.
Wonderful continue! The European Union Against Rheumatism (EULAR) conference in 2021 will be held online, and rheumatology immunologists and doctors around the world will enjoy this academic feast
.
The "Medical Channel of Rheumatology and Kidney Disease" and a group of authoritative experts from Peking University People's Hospital will provide timely conference reports for everyone, and grasp the latest and hottest international frontier developments in the field of rheumatology immunology for the first time
.
01Professor Kristina Lejon from the University of Umeå in Sweden gave the title of “Decreased Levels of T Follicular Helper (CD4+CXCR5+) Cells and CD27+CD38+and CD27+CD38- B Cells in Ankylosing Spondylitis Patients Correlate with Marker of Inflammation" report, introduced the study of the correlation between CD4+CXCR5+ Tfh cells, CD27+CD38+ and CD27+CD38- B cells and the inflammatory state of patients with ankylosing spondylitis (AS)
.
By performing flow cytometry on CD4+CXCR5+ Tfh cells and CD27+CD38+ and CD27+CD38- B cells in the peripheral blood of AS patients with different genders and healthy controls, they found that these three groups of cells in AS patients were significantly reduced compared with healthy controls, and Observed in female patients, there is a significant correlation with the Bath AS Measurement Index (BASMI), which may be involved in the pathogenesis of AS
.
Figure 1: Tfh cell reduction in AS patients Figure 2: Abnormal B cell differentiation in AS patients Dr.
Viviana Marzaioli from University College Dublin, National University of Ireland, brought the title "CD209+/CD14+Dendritic Cells are enriched and activated at the site of inflammation and are modulated "by JAK/STAT signalling" report, introduced the pathogenic role of CD209+/CD14+ DC cells in inflammatory arthritis (IA)
.
Taking rheumatoid arthritis (RA) and psoriatic arthritis (PsA) and other IA peripheral blood and joint synovium as the research object, they found that there are CD209+/CD14+ DC cell subsets in the peripheral blood of patients with active IA, and This group of cells can infiltrate the joints of patients with RA and PsA
.
Further research found that JAK/STAT inhibitors can target this group of pathogenic DC cells, while tumor necrosis factor (TNF) inhibitors are ineffective
.
Figure 3: Overactivation of CD209+/CD14+ DC cell subsets in the peripheral blood of IA patients Figure 4: JAK/STAT inhibitors target to inhibit pathogenic CD209+/CD14+ DC cell subsets brought by Dr.
Megan Hanlon from the University College of Dublin, National University of Ireland The report titled "CD206+CD163+pathogenic macrophages enriched in Rheumatoid Arthritis synovial tissue with distinct transcriptional signatures" introduced the role and mechanism of CD206+CD163+ macrophages in the pathogenesis of RA
.
Studies have found that CD206+CD163+ macrophages are the main group of macrophages in the synovial tissues of normal people and RA patients
.
In the RA state, this group of cells is significantly enriched in synovial tissues, highly expressing CD40, and is positively correlated with DAS28
.
RNA-seq results show that the gene expression profile of CD206+CD163+ macrophages in RA synovial tissue is significantly different from that of CD206-CD163-macrophages, and is significantly different from peripheral blood M1 and M2 cells, showing a unique transcriptome Features
.
The results of metabonomic analysis also showed that CD206+CD163+ macrophages are a unique group of macrophages with a characteristic metabolic phenotype
.
Functional studies have further found that CD206+CD163+ macrophages express a variety of inflammatory factors and play an important role in the inflammatory lesions of RA synovial tissue
.
Figure 5: The role and mechanism of CD206+CD163+ macrophages in the pathogenesis of RA 02 Immune Molecules Dr.
Eric Malmhall-Bah from the University of Gothenburg in Sweden brought a report titled "Rho expression facilitates T cell migration to lymph nodes in response inflammation", The role of GGTase-I deficient macrophages in activating Rho protein-dependent CD4+ T cell migration in the pathogenesis of arthritis is introduced
.
They constructed macrophage GGTase-I conditional knockout mice (GLC mice).
Studies have suggested that GLC mice will exhibit excessive activation of Rho protein and erosive arthritis similar to RA
.
They further researched and found that T cells play an important role in arthritis in GLC mice, CD4+ T cells in GLC mice exhibit unique characteristics, and Rho protein in macrophages can affect CD4+ T cells in GLC mice
.
In addition, the use of CTLA4-FP to interfere with the interaction between macrophages and T cells will reduce T cell activation in GLC mice and the inflammatory phenotype of mice
.
Figure 6: GLC mouse CD4+ T cells exhibit unique immunological characteristics.
Professor Maria I Bokarewa from the University of Gothenburg in Sweden brought a report entitled "IGF1R dependent cell interaction and regulation of autoantibody production in rheumatoid arthritis", introducing insulin-like growth The study of the key role of factor 1 receptor (IGF1R) signaling in cell communication and antibody production
.
They found that inhibition of IGF1R would lead to the expansion of CD21+ antigen-presenting cells and a significant reduction in the expression of ICOSL; inhibition of IGF1R would also lead to the expansion of the marginal zone and the aggregation of IgM+CD21+ B cells in the marginal zone; in addition, inhibition of IGF1R It can also lead to the production of a variety of autoantibodies such as anti-CCP, RF, and anti-DNA
.
Figure 7: Inhibition of IGF1R leads to the accumulation of IgM+CD21+ B cells in the marginal zone.
Figure 8: Inhibition of IGF1R leads to the production of autoantibodies.
03 New immunomodulatory drugs Dr.
Jyothsna Visweswaraiah of Merck, USA brought the title "Generation of PT101, a highly The report "selective IL-2 mutein for treatment of autoimmune diseases" introduced the application research of a highly selective mutant IL-2—PT101 in the treatment of autoimmune diseases
.
PT101 was developed by replacing asparagine at position 88 of IL-2 to reduce its affinity with IL-2Rβ, and then through structural modification to increase its affinity with IL-2Rα, and then endow it with the characteristics of a drug
.
Studies have shown that PT101 can selectively increase Treg cells without affecting NK cells
.
In vitro experiments in humans and rhesus monkeys have shown that PT101 can selectively increase Treg in a dose-dependent manner; experiments in healthy volunteers have also shown that PT101 can increase total Treg and CD25bright Treg without affecting NK cells and Pro-inflammatory T cells
.
These findings suggest that PT101 can be considered as a treatment option for autoimmune diseases such as SLE
.
Figure 9: Construction of highly selective mutant IL-2--PT101 Figure 10: Compared with wild-type IL-2, PT101 selectively activates human and rhesus monkey Treg cells in vitro.
Dr.
Ivan Zvyagin of the University brought a report titled "AS-related TCR beta clonotypes are present in different inflamed tissues of patients with spondyloarthropathies", introducing different types of spondyloarthritis (SpA) patients with different tissue ankylosing spondylitis (AS) Related TCR beta clonotype research
.
They treated a variety of SpA (including AS, PsA, juvenile idiopathic arthritis) and combined extra-articular manifestations (ulcerative colitis, Crohn’s disease and uveitis) patients with peripheral blood, joint fluid, intestinal tissue and Conjunctival swabs were subjected to TCR sequencing, and HLA-B27 typing was tested
.
The results showed that the AS-related bTCR clonotypes that have been found so far are widespread in the synovial fluid of different types of SpA patients, and there is a strong correlation with the genotype of HLA-B27
.
Interestingly, AS-related bTCR clones can also be detected in other sites of inflammation in patients with SpA with extra-articular manifestations, such as the small intestine of patients with IBD and the conjunctiva of patients with uveitis
.
Figure 11: AS-related bTCR clonotypes are commonly found in the synovial fluid of different types of SpA patients.
Figure 12: AS-related bTCR clones can also be detected in other inflammation sites of SpA patients with extra-articular manifestations.
Hu Fanlei commented on rheumatism Immune disease is an autoimmune disease with a complex pathogenesis, which not only includes a large number of activation of natural immune response, but also involves excessive activation of adaptive immune response
.
Innate immune cells such as monocytes/macrophages, dendritic cells, mast cells, natural killer cells, and adaptive immune cells such as T cells and B cells all play an important role in the pathogenesis of rheumatism
.
In addition to the classic subpopulations, the identification of new immune cell subpopulations is a major trend in immunological research at present, which will provide new clues for the in-depth understanding of the pathogenesis of rheumatism and immunotherapy strategies; and the tissue-specific new immune system Cell research will further provide help for the immunological diagnosis and treatment of organ-specific rheumatic immune diseases
.
The breaking of immune homeostasis and the activation of autoimmunity are the key and initiating link of the onset of rheumatoid immune diseases.
Immune balance therapy is one of the fundamental ways to achieve the remission of rheumatoid immune diseases
.
Research conducted by the Rheumatology Team of Peking University People's Hospital and several teams at home and abroad led by Professor Li Zhanguo has shown that low-dose IL-2 has great advantages in restoring immune balance and treating rheumatism, especially SLE, and has been clinically applied
.
Further transformation and upgrading of the drug to improve its efficacy and stability will have important clinical significance and application prospects
.
Some studies have shown that TCR and BCR of rheumatoid diseases such as RA and SLE exhibit unique variable region characteristics and present some dominant sequences
.
With the maturity and improvement of immune repertoire technology, the systematic analysis of TCR and BCR repertoire of rheumatoid immune diseases and identification of their dominant sequences will have important theoretical guiding significance for the development of antibody drugs and the design of therapeutic TCR/BCR peptide vaccines.
And application value
.
Expert profile Hu Fanlei, Department of Rheumatology and Immunology, Peking University People’s Hospital/Beijing Key Laboratory of Rheumatology, Associate Researcher, Doctoral Supervisor, Deputy Secretary-General of the Clinical Immunization Branch of the Chinese Society of Immunology, Youth Committee ENDOCR METAB IMMUNE Magazine Section Editor, Frontiers in Immunology, Experimental and The editorial board member of Therapeutic Medicine, Beijing Science and Technology Rising Star China Immunology Academic Award-Young Scholar Award winner, has long been engaged in research on the pathogenesis of autoimmune diseases (especially rheumatoid arthritis) and immunological diagnosis and treatment, and has achieved a series of innovative results for nearly 5 years.
The first/corresponding author has published 22 SCI papers, including Nature Communications, Annals of the Rheumatic Diseases, Journal of Autoimmunity, Journal of Immunology, European Journal of Immunology, etc.
Undertake the National Natural Science and Youth Project, Beijing Science and Technology New Star Project, etc.
More than 10 projects; jointly undertake 1 project of the National Natural Science Research Plan.
Obtained (please) 6 national invention patents.
Received multiple scientific research awards, including the first prize of the University Science and Technology Progress Award, the second prize of the Chinese Medical Science and Technology Award, etc.
