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*Only for medical professionals to read and refer to the first article of the conference, it is still hot! 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" combined with authoritative experts from Peking University People's Hospital to report on the meeting in a timely manner, and to grasp the latest and hottest international frontier developments in the field of rheumatology and immunology for the first time
.
In the special session on the molecular mechanism of connective tissue disease, 8 experts and scholars in this field from top hospitals around the world shared special reports and multimedia presentations with us, and conducted in-depth discussions on hotspots, difficult issues and latest developments in disease treatment
.
People's knowledge and understanding of connective tissue diseases including systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS) has gone through a very long process
.
It is now generally believed that SLE is a complex inflammatory autoimmune disease, which is mainly characterized by immune regulatory dysfunction.
Its onset is related to genetic environmental factors, estrogen levels in the body and many other factors, and it is more common for young women
.
One of the characteristics of SLE is the appearance of multiple autoantibodies
.
Just like the name of the disease, SLE can damage multiple systems and multiple organs, so the clinical manifestations of patients are diverse and difficult to heal
.
SS is a chronic systemic autoimmune disease.
In addition to the involvement of the exocrine glands, there will be many extra-glandular manifestations, such as systemic lymphadenopathy, kidney damage, and neurological, lung, joint, skin, and muscle diseases and so on
.
With the rapid advancement of research, our understanding of diseases has been continuously improved in the past two to three decades, including the discovery of disease genetics, pathogenesis, key cytokines and therapeutic drugs, which have greatly improved the diagnosis rate and The level of treatment
.
01 Molecular Splicing and Clinical Activity Professor Chary Lopez-Pedrera from the University of Cordoba in Spain brought the title "Splicesome alterations in leukocytes from patients with antiphospholipid syndrome, systemic lupus erythematosus and antiphospholipid syndrome with lupus patients are closely related to their main clinical features" report
.
At present, the genetic factors of patients with systemic autoimmune diseases with multiple antibodies, susceptibility to thrombosis, or organ involvement are still unknown, and the relevant research on the post-transcriptional mechanism is still lacking
.
Therefore, it is very important to identify the common and unique splicing mechanism of immune cells in patients with APS, SLE and SLE combined with APS, and the correlation with the clinical manifestations of these immune diseases
.
The researchers recruited 50 healthy people and patients with related diseases to explore the molecular changes on their lymphocytes, neutrophils and monocytes and the mechanisms of these changes
.
Studies have shown that the leukocyte splicing mechanism of patients with APS, SLE, APS and SLE has changed and is related to clinical disease activities.
The analysis of the mechanism also explains the unique composition of cardiovascular and renal involvement in these diseases
.
Figure 1: Changes in the splicing mechanism of leukocytes in patients with APS, SLE, APS and SLE.
02 Cytokine-a new therapeutic target Cytokine has been recognized as an important mediator of inflammation and joint damage in rheumatic immune diseases.
The mechanism of cytokine action and its mechanism Targeted therapy is a hot research direction that clinical and scientific researchers pay attention to
.
Dr.
Stacey Dillon introduced the important role of ALPN-303 in the treatment of SLE and other B cell-related diseases
.
BAFF/APRIL is an important cytokine in the differentiation and development of B cells.
ALPN-303, as a BAFF/APRIL antagonist, has attracted the attention of scientists
.
Cell experiments and animal experiments have proved that ALPN-303 can inhibit B cell survival and disease activity more than TACI-Fc, reflecting a good immune regulation effect
.
Professor Yan Po Tsao from Taiwan Veterans General Hospital introduced that NLPR12 may be a biomarker of disease activity in SLE patients.
NLPR12 is negatively correlated with interferon expression.
At the same time, the team also discovered a potential transcription factor TF-1 that can be negative.
Regulating the expression of NLPR12 and the correlation of interferon signaling in lupus
.
At present, the level of CXCL13 in the serum and saliva of SS patients is getting more and more attention.
Loukas Chatzis of the National University of Capodistria in Athens, Greece recruited multiple groups of patients with primary Sjogren’s syndrome (pSS) and In healthy controls, the detection of CXCL13 levels in their ectopic germinal centers, serum and saliva, etc.
, proved that CXCL13 is related to the severity of salivary gland lesions and lymphoma in patients with SS, and that CXCL13 in serum is closely related to pathology, clinical manifestations and predicting the development of NHL Related
.
Figure 2: ALPN-303 can inhibit B cell survival and disease activity more than TACI-Fc Figure 3: The potential transcription factor TF-1 can negatively regulate the expression of NLPR12 Figure 4: CXCL13 in serum is related to clinical and laboratory indicators , 03 Immune cells-maintain the body's immune balance Nikolopoulos D from the National University of Capodistria in Athens introduced the NZB/W lupus model that can reproduce the performance of neuropsychiatric lupus erythematosus, the small glue in the hippocampus of lupus mice The shift of the plasma cell population to the activated state may lead to increased antigen presentation
.
The hippocampus in patients with lupus may be a target organ of the immune system, which can lead to decreased serotonin synthesis and decreased norepinephrine levels
.
Subsequently, Dr.
Daniele Mauro from the University of Campania introduced the concept of memory T cells (TRM), which has recently been recognized as a lymphatic system that enters the tissues rather than the circulation.
It does not respond to antigen responses and immediately produces effector functions.
, Plays an important role in the pathogenesis of pSS
.
Studies have shown that TRM that expresses CD103 in pSS patients is significantly increased and participates in the inflammation of tissues and organs.
Anti-CD103 treatment can well alleviate the performance of pSS
.
Figure 5: TRM expressing CD103 in pSS patients increased significantly.
04 Clinical studies-evaluation of preventive diagnosis and treatment.
At present, many studies have explored the relationship between infection and SLE, but there are survival deviations.
Only health and survival are considered, while previous infections and deaths are not Included, so it is not universal
.
Dr.
Kai Zhao from Simon Fraser University in Canada pointed out that the main cause of death for SLE patients is infection, whether in the early or late course of the disease
.
They conducted an SLE cohort study based on a large sample.
The study showed that 1/5 of SLE patients had serious infections; 21% of the mortality rate was related to infection
.
At the same time, compared with non-SLE, the risk of severe infection in SLE patients has increased by 82%, and the infection-related mortality rate of SLE has increased by 62%.
.
In addition, Professor Sabih UI Hassan from the Leeds Institute of Rheumatology and Musculoskeletal Medicine introduced the relationship between ANA antibodies and individuals without clinical autoimmune diseases
.
The researchers conducted annual long-term follow-up of 150 high-risk individuals, and compared and analyzed individuals who had progressed and those who did not.
The study showed that a large proportion of ANA-positive people developed clinically major diseases.
Although SLE standards are not applicable, they have also proven to exceed Three years of ANA positive without clinical criteria is associated with a major immune imbalance
.
Figure 6: ANA positives without clinical standards for more than 3 years are related to major immune imbalance.
At present, with the development of basic medicine, our understanding of autoimmune diseases has deepened from clinical to immune mechanism, exploring the molecules of connective tissue disease Mechanism has become an important direction and upsurge of modern rheumatic immune disease research
.
Various immune cells, cytokines, small molecules and their unique multi-target pathways provide an important cornerstone for the in-depth study of the pathogenesis of rheumatic immune diseases and the development of clinical diagnosis and treatment
.
The pursuit of targeted mechanisms.
The treatment of precise targets has brought innovations in clinical treatment.
At present, the emergence of biological agents and targeted drugs for various cells and molecules has a milestone significance for the treatment of rheumatic immune diseases
.
However, although these drugs combined with conventional therapeutic drugs such as glucocorticoids and immunosuppressants can effectively improve the survival rate and quality of life of some patients with connective tissue diseases, some patients still have not been relieved clinically.
Clinicians and basic researchers should still Continue to actively explore more effective and safer treatment options to benefit more patients
.
Expert profile Professor Jing He Chief physician, professor, and doctoral supervisor of the Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing Science and Technology Rising Star, National Youth Science and Technology Innovation Leader, National Ten Thousand Talents Program, Mao Yisheng, Beijing Youth Science and Technology Award, Clin Rheum, Deputy Chief Editor, Chinese Medical Association Young committee member of the Rheumatology Branch Young committee member of the Chinese Society of Immunology Main research results As a clinical research physician, dedicated to the clinical and basic research of autoimmune diseases such as systemic lupus erythematosus and Sjogren’s syndrome
.
Precursor follicular helper T cells and their pathogenic mechanisms have been discovered in patients with rheumatoid arthritis; the application of low-dose interleukin-2 in the treatment of systemic lupus erythematosus has been successful, and studies have found that this new immunotherapy method can effectively control patients with lupus erythematosus And research has proved the mechanism of interleukin-2 to regulate immune balance and treat autoimmune diseases
.
As the first author, his research results have been published in Immunity (IF 19.
7), Nature Medicine (IF 30.
357), Ann Rheum Dis, Rheumatism Yearbook (IF 14.
29) and Lancet Rheum.
He has published more than 90 papers, including more than 40 SCI papers, and has been invited to write reviews for journals such as Nat Rev Rheum and Clin Rheum.
He has spoken at many international conferences
.
.
The "Medical Channel of Rheumatology and Kidney Disease" combined with authoritative experts from Peking University People's Hospital to report on the meeting in a timely manner, and to grasp the latest and hottest international frontier developments in the field of rheumatology and immunology for the first time
.
In the special session on the molecular mechanism of connective tissue disease, 8 experts and scholars in this field from top hospitals around the world shared special reports and multimedia presentations with us, and conducted in-depth discussions on hotspots, difficult issues and latest developments in disease treatment
.
People's knowledge and understanding of connective tissue diseases including systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS) has gone through a very long process
.
It is now generally believed that SLE is a complex inflammatory autoimmune disease, which is mainly characterized by immune regulatory dysfunction.
Its onset is related to genetic environmental factors, estrogen levels in the body and many other factors, and it is more common for young women
.
One of the characteristics of SLE is the appearance of multiple autoantibodies
.
Just like the name of the disease, SLE can damage multiple systems and multiple organs, so the clinical manifestations of patients are diverse and difficult to heal
.
SS is a chronic systemic autoimmune disease.
In addition to the involvement of the exocrine glands, there will be many extra-glandular manifestations, such as systemic lymphadenopathy, kidney damage, and neurological, lung, joint, skin, and muscle diseases and so on
.
With the rapid advancement of research, our understanding of diseases has been continuously improved in the past two to three decades, including the discovery of disease genetics, pathogenesis, key cytokines and therapeutic drugs, which have greatly improved the diagnosis rate and The level of treatment
.
01 Molecular Splicing and Clinical Activity Professor Chary Lopez-Pedrera from the University of Cordoba in Spain brought the title "Splicesome alterations in leukocytes from patients with antiphospholipid syndrome, systemic lupus erythematosus and antiphospholipid syndrome with lupus patients are closely related to their main clinical features" report
.
At present, the genetic factors of patients with systemic autoimmune diseases with multiple antibodies, susceptibility to thrombosis, or organ involvement are still unknown, and the relevant research on the post-transcriptional mechanism is still lacking
.
Therefore, it is very important to identify the common and unique splicing mechanism of immune cells in patients with APS, SLE and SLE combined with APS, and the correlation with the clinical manifestations of these immune diseases
.
The researchers recruited 50 healthy people and patients with related diseases to explore the molecular changes on their lymphocytes, neutrophils and monocytes and the mechanisms of these changes
.
Studies have shown that the leukocyte splicing mechanism of patients with APS, SLE, APS and SLE has changed and is related to clinical disease activities.
The analysis of the mechanism also explains the unique composition of cardiovascular and renal involvement in these diseases
.
Figure 1: Changes in the splicing mechanism of leukocytes in patients with APS, SLE, APS and SLE.
02 Cytokine-a new therapeutic target Cytokine has been recognized as an important mediator of inflammation and joint damage in rheumatic immune diseases.
The mechanism of cytokine action and its mechanism Targeted therapy is a hot research direction that clinical and scientific researchers pay attention to
.
Dr.
Stacey Dillon introduced the important role of ALPN-303 in the treatment of SLE and other B cell-related diseases
.
BAFF/APRIL is an important cytokine in the differentiation and development of B cells.
ALPN-303, as a BAFF/APRIL antagonist, has attracted the attention of scientists
.
Cell experiments and animal experiments have proved that ALPN-303 can inhibit B cell survival and disease activity more than TACI-Fc, reflecting a good immune regulation effect
.
Professor Yan Po Tsao from Taiwan Veterans General Hospital introduced that NLPR12 may be a biomarker of disease activity in SLE patients.
NLPR12 is negatively correlated with interferon expression.
At the same time, the team also discovered a potential transcription factor TF-1 that can be negative.
Regulating the expression of NLPR12 and the correlation of interferon signaling in lupus
.
At present, the level of CXCL13 in the serum and saliva of SS patients is getting more and more attention.
Loukas Chatzis of the National University of Capodistria in Athens, Greece recruited multiple groups of patients with primary Sjogren’s syndrome (pSS) and In healthy controls, the detection of CXCL13 levels in their ectopic germinal centers, serum and saliva, etc.
, proved that CXCL13 is related to the severity of salivary gland lesions and lymphoma in patients with SS, and that CXCL13 in serum is closely related to pathology, clinical manifestations and predicting the development of NHL Related
.
Figure 2: ALPN-303 can inhibit B cell survival and disease activity more than TACI-Fc Figure 3: The potential transcription factor TF-1 can negatively regulate the expression of NLPR12 Figure 4: CXCL13 in serum is related to clinical and laboratory indicators , 03 Immune cells-maintain the body's immune balance Nikolopoulos D from the National University of Capodistria in Athens introduced the NZB/W lupus model that can reproduce the performance of neuropsychiatric lupus erythematosus, the small glue in the hippocampus of lupus mice The shift of the plasma cell population to the activated state may lead to increased antigen presentation
.
The hippocampus in patients with lupus may be a target organ of the immune system, which can lead to decreased serotonin synthesis and decreased norepinephrine levels
.
Subsequently, Dr.
Daniele Mauro from the University of Campania introduced the concept of memory T cells (TRM), which has recently been recognized as a lymphatic system that enters the tissues rather than the circulation.
It does not respond to antigen responses and immediately produces effector functions.
, Plays an important role in the pathogenesis of pSS
.
Studies have shown that TRM that expresses CD103 in pSS patients is significantly increased and participates in the inflammation of tissues and organs.
Anti-CD103 treatment can well alleviate the performance of pSS
.
Figure 5: TRM expressing CD103 in pSS patients increased significantly.
04 Clinical studies-evaluation of preventive diagnosis and treatment.
At present, many studies have explored the relationship between infection and SLE, but there are survival deviations.
Only health and survival are considered, while previous infections and deaths are not Included, so it is not universal
.
Dr.
Kai Zhao from Simon Fraser University in Canada pointed out that the main cause of death for SLE patients is infection, whether in the early or late course of the disease
.
They conducted an SLE cohort study based on a large sample.
The study showed that 1/5 of SLE patients had serious infections; 21% of the mortality rate was related to infection
.
At the same time, compared with non-SLE, the risk of severe infection in SLE patients has increased by 82%, and the infection-related mortality rate of SLE has increased by 62%.
.
In addition, Professor Sabih UI Hassan from the Leeds Institute of Rheumatology and Musculoskeletal Medicine introduced the relationship between ANA antibodies and individuals without clinical autoimmune diseases
.
The researchers conducted annual long-term follow-up of 150 high-risk individuals, and compared and analyzed individuals who had progressed and those who did not.
The study showed that a large proportion of ANA-positive people developed clinically major diseases.
Although SLE standards are not applicable, they have also proven to exceed Three years of ANA positive without clinical criteria is associated with a major immune imbalance
.
Figure 6: ANA positives without clinical standards for more than 3 years are related to major immune imbalance.
At present, with the development of basic medicine, our understanding of autoimmune diseases has deepened from clinical to immune mechanism, exploring the molecules of connective tissue disease Mechanism has become an important direction and upsurge of modern rheumatic immune disease research
.
Various immune cells, cytokines, small molecules and their unique multi-target pathways provide an important cornerstone for the in-depth study of the pathogenesis of rheumatic immune diseases and the development of clinical diagnosis and treatment
.
The pursuit of targeted mechanisms.
The treatment of precise targets has brought innovations in clinical treatment.
At present, the emergence of biological agents and targeted drugs for various cells and molecules has a milestone significance for the treatment of rheumatic immune diseases
.
However, although these drugs combined with conventional therapeutic drugs such as glucocorticoids and immunosuppressants can effectively improve the survival rate and quality of life of some patients with connective tissue diseases, some patients still have not been relieved clinically.
Clinicians and basic researchers should still Continue to actively explore more effective and safer treatment options to benefit more patients
.
Expert profile Professor Jing He Chief physician, professor, and doctoral supervisor of the Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing Science and Technology Rising Star, National Youth Science and Technology Innovation Leader, National Ten Thousand Talents Program, Mao Yisheng, Beijing Youth Science and Technology Award, Clin Rheum, Deputy Chief Editor, Chinese Medical Association Young committee member of the Rheumatology Branch Young committee member of the Chinese Society of Immunology Main research results As a clinical research physician, dedicated to the clinical and basic research of autoimmune diseases such as systemic lupus erythematosus and Sjogren’s syndrome
.
Precursor follicular helper T cells and their pathogenic mechanisms have been discovered in patients with rheumatoid arthritis; the application of low-dose interleukin-2 in the treatment of systemic lupus erythematosus has been successful, and studies have found that this new immunotherapy method can effectively control patients with lupus erythematosus And research has proved the mechanism of interleukin-2 to regulate immune balance and treat autoimmune diseases
.
As the first author, his research results have been published in Immunity (IF 19.
7), Nature Medicine (IF 30.
357), Ann Rheum Dis, Rheumatism Yearbook (IF 14.
29) and Lancet Rheum.
He has published more than 90 papers, including more than 40 SCI papers, and has been invited to write reviews for journals such as Nat Rev Rheum and Clin Rheum.
He has spoken at many international conferences
.
