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*Only for medical professionals to read for reference Want to easily understand the progress of BD? Must read! In recent years, the frontiers of Behcet’s disease/syndrome (BD/BS, hereinafter referred to as BD) have emerged endlessly.
At the “First National Clinical Research Center for Skin and Immune Diseases Annual Meeting” jointly sponsored by China Systemic Lupus Erythematosus Research Collaboration Group (CSTAR), National Rheumatism Data Center (CRDC) and China Rheumatology and Immunology Medical Association (CRCA) At the CSTAR/CRDC/CRCA Annual Conference", Director Zheng Wenjie of the Department of Rheumatology and Immunology of Peking Union Medical College Hospital sorted out the latest research according to the pathogenesis, clinical manifestations and treatment of BD.
Let us take a look! Progress 1: Innate immunity is more important than we think in the development of BD.
In recent years, the understanding of BD is more inclined to think that it is a polygenic auto-inflammatory disease.
Its outstanding features are the same as auto-inflammatory diseases, including Toll-like receptors (TLRs) signaling pathway, activation of natural immune cells and super inflammatory response, overexpression of pro-inflammatory cytokines.
1 Overactivation and infiltration of neutrophils-a crucial link, a review published on Front lmmunol last year "Understanding Behcet's Disease in the Context of Innate Immunity Activation" recognized the importance of innate immunity and emphasized The excessive activation and infiltration of neutrophils at the injured site is a crucial part in the recurrent acute inflammation of BD.
Figure 1 An article published on Front lmmunol.
Excessive activation and infiltration of neutrophils at the injured site is one of the main features of recurrent acute inflammation in BD.
In patients with BD, acupuncture-reaction epidermis, panniculitis, submucosal blood vessel wall or thrombus in the heart can be seen infiltration of inflammatory cells, mainly neutrophils.
Figure 3 Infiltration of inflammatory cells dominated by neutrophils.
Previous studies have shown that both sebum panniculitis and inflamed vascular tissues of BD patients can express neutrophil extracellular capture network (NETs), that is, neutrophils are in inflammatory conditions.
The fibrous net-like structure released to the outside of the cell when the phase is activated, and the article published by Professor Zheng Wenjie in Front Immunol in 2021 further confirms that the neutrophils of BD patients are stimulated by phorbol lipid (PMA) or without stimulation.
In all cases, more NETs are produced than normal people.
Figure 3 Neutrophils in patients with BD produce more NETs than normal people under PMA stimulation or without stimulation.
In addition, NETs in patients with BD stimulate macrophages to secrete interleukin-8 (IL-8) and tumor necrosis The level of factor-α (TNF-α) was significantly higher than that of the normal population, and the ability of BD to promote IFN-y+CD4+T cell differentiation was also enhanced.
The content of histone H4 in NETs in BD patients is higher than that in normal people.
After blocking histone H4 in NETs, the level of IL-8 produced by BD NETs stimulated by macrophages will be reduced.
2 Abnormal monocytes Monocytes are the bridge between innate immunity and adaptive immunity.
In 2020, a study published by Professor Wenjie Zheng on clin immunol showed that monocytes in patients with BD have an imbalance of Fcy receptor (Ig Fc fragment binding receptor), and this imbalance is related to disease activity.
Figure 4 Fcy receptor imbalance exists in monocytes of BD patients.
In addition, there are also abnormalities in BD monocyte subpopulations.
IM increases and NCM decreases.
These two are also closely related to the disease activity of BD.
Figure 5 Abnormality of BD monocyte subpopulations.
In addition, BD-CM and IM secrete pro-inflammatory cytokines increased, and BD-CM promotes Th1 differentiation.
Progress 2: BD has the same inflammation path as autoinflammatory diseases, and the clinical features overlap each other.
1 Clinical manifestations, men and women are "different", 40 years old is a "division line" The clinical features of BD and hereditary autoinflammatory diseases overlap each other.
It can be manifested as mucosal ulcers, joint disease, and uveitis.
In addition, the inflammation recurred and relieved repeatedly, and there was no obvious triggering factor for the attack.
Last year, a study by Professor Zheng Wenjie and others showed that the male to female ratio of BD patients in my country was about 1.
41, with a median age of 34 years.
Male patients often present with ophthalmitis, vascular involvement, pseudofolliculitis, and acupuncture reactions; female patients have more common genital ulcers.
Vascular lesions and gastrointestinal ulcers are common in patients over 40 years old, while pseudofolliculitis and acne-like rash are common in patients under 40 years old.
2 Involvement of large vessels accounts for "half of the cause of death" Among the main causes of death in BD patients in my country, the main cause of involvement of large vessels (54.
2%), including ruptured aneurysms, venous thrombosis/occlusion, and severe valve disease.
Figure 6 The main cause of death of BD patients in my country is very important due to the involvement of large blood vessels in BD, and it has also been included in the 2014 new International Standards for Behcet's Disease (ICBD).
BD complicated with heart valve disease has an insidious onset, lack of specificity in cardiac performance, with moderate/severe aortic insufficiency (ascending aortic dilation or aneurysm, valve prolapse, neoplastic formation, valve perforation or tear, and paravalvular abscess ) Mainly, less involving the mitral and tricuspid valves.
The risk of postoperative complications of BD combined with valvular disease is extremely high (49.
2%-100%), mainly including repeated paravalvular leaks and anastomotic aneurysms.
After complications occur, the mortality rate is as high as 60%, and the risk of reoperation is as high as 30%-90%.
Studies have also shown that the control of the primary disease in the perioperative period is closely related to the incidence of complications such as postoperative paravalvular leakage.
All of these conditions can increase the risk of postoperative paravalvular leaks and other complications: no immunosuppressive agents were used before surgery; preoperative CTX accumulation was low; preoperative erythrocyte sedimentation rate (ESR) was significantly increased; no postoperative use Immunosuppressive agent.
Progress 3: Progress in BD drug treatment 1 What is the effect of interferon on BD uveitis? According to the latest EULAR guidelines for clinical management of Behçet’s syndrome in 2018, TNF-α inhibitors are drugs with a higher level of evidence for the treatment of BD.
However, there are also some contraindications for the monoclonal antibody TNF-α, such as recurrence of tuberculosis, Combined with HBV infection and so on. This requires researchers to focus on drugs other than TNF-α inhibitors.
In 2019, Professor Wenjie Zheng published a study on the use of interferon combined with hormone immunosuppressants to treat refractory BD uveitis.
Figure 7 In 2019, Professor Wenjie Zheng published a study on Therapeutic Advances in Chronic Disease.
This study is the first domestic and foreign research report on the use of IFNα-2a combined with hormones and immunosuppressive agents for refractory BD uveitis, and proves this The therapy is safe, effective and inexpensive.
Professor Zheng Wenjie believes that this therapy can be recommended as the first-line treatment for refractory BD uveitis in the Chinese population.
2secukinumab anti-interleukin-17A monoclonal antibody In 2020, a multi-center study on the long-term effectiveness and safety of secukinumab (an IL-17A monoclonal antibody) on refractory mucosa and joint BD was published in Ann Rheum On Dis.
Figure 8 The study published in Ann Rheum Dis in 2020.
The study believes that the treatment of secukinumab 300mg/m has certain benefits for oral ulcers and arthritis, as well as scrotal ulcers, axial arthritis and intestinal lesions.
beneficial.
3MAGIC syndrome, which biologics is better? The syndrome in which BD and recurrent polychondritis (RP) coexist is called MAGIC syndrome.
For this part of patients, Professor Zheng Wenjie found through research that infliximab (IFX) is effective, while tocilizumab (TCZ) The curative effect is not satisfactory.
Summary: In recent years, the research on BD has made fruitful progress from the molecular level to the clinical treatment.
As the core force in the field of rheumatology and immunology in my country, the team led by Professor Zheng Wenjie has made outstanding contributions to the research of BD.
At this conference, Professor Zheng Wenjie Luo listed many outstanding recent achievements, such as innate immunity is very important in the occurrence and development of BD, especially the excessive activation and infiltration of neutrophils; and monocyte Fcy receptors The imbalance is related to the activity of the disease.
BD has the same inflammation path as autoinflammatory diseases, and the clinical features overlap with each other.
Large vessel involvement is the main cause of death in BD patients in my country, while heart valve disease has an insidious onset, but the risk of postoperative complications is extremely high (49.
2%-100 %), and the mortality rate after complications is as high as 60%.
On the treatment level, Professor Zheng Wenjie recommended interferon combined with hormones and immunosuppressants as the first-line treatment for refractory BD uveitis in the Chinese population.
Looking forward to more outstanding achievements in 2021.
At the “First National Clinical Research Center for Skin and Immune Diseases Annual Meeting” jointly sponsored by China Systemic Lupus Erythematosus Research Collaboration Group (CSTAR), National Rheumatism Data Center (CRDC) and China Rheumatology and Immunology Medical Association (CRCA) At the CSTAR/CRDC/CRCA Annual Conference", Director Zheng Wenjie of the Department of Rheumatology and Immunology of Peking Union Medical College Hospital sorted out the latest research according to the pathogenesis, clinical manifestations and treatment of BD.
Let us take a look! Progress 1: Innate immunity is more important than we think in the development of BD.
In recent years, the understanding of BD is more inclined to think that it is a polygenic auto-inflammatory disease.
Its outstanding features are the same as auto-inflammatory diseases, including Toll-like receptors (TLRs) signaling pathway, activation of natural immune cells and super inflammatory response, overexpression of pro-inflammatory cytokines.
1 Overactivation and infiltration of neutrophils-a crucial link, a review published on Front lmmunol last year "Understanding Behcet's Disease in the Context of Innate Immunity Activation" recognized the importance of innate immunity and emphasized The excessive activation and infiltration of neutrophils at the injured site is a crucial part in the recurrent acute inflammation of BD.
Figure 1 An article published on Front lmmunol.
Excessive activation and infiltration of neutrophils at the injured site is one of the main features of recurrent acute inflammation in BD.
In patients with BD, acupuncture-reaction epidermis, panniculitis, submucosal blood vessel wall or thrombus in the heart can be seen infiltration of inflammatory cells, mainly neutrophils.
Figure 3 Infiltration of inflammatory cells dominated by neutrophils.
Previous studies have shown that both sebum panniculitis and inflamed vascular tissues of BD patients can express neutrophil extracellular capture network (NETs), that is, neutrophils are in inflammatory conditions.
The fibrous net-like structure released to the outside of the cell when the phase is activated, and the article published by Professor Zheng Wenjie in Front Immunol in 2021 further confirms that the neutrophils of BD patients are stimulated by phorbol lipid (PMA) or without stimulation.
In all cases, more NETs are produced than normal people.
Figure 3 Neutrophils in patients with BD produce more NETs than normal people under PMA stimulation or without stimulation.
In addition, NETs in patients with BD stimulate macrophages to secrete interleukin-8 (IL-8) and tumor necrosis The level of factor-α (TNF-α) was significantly higher than that of the normal population, and the ability of BD to promote IFN-y+CD4+T cell differentiation was also enhanced.
The content of histone H4 in NETs in BD patients is higher than that in normal people.
After blocking histone H4 in NETs, the level of IL-8 produced by BD NETs stimulated by macrophages will be reduced.
2 Abnormal monocytes Monocytes are the bridge between innate immunity and adaptive immunity.
In 2020, a study published by Professor Wenjie Zheng on clin immunol showed that monocytes in patients with BD have an imbalance of Fcy receptor (Ig Fc fragment binding receptor), and this imbalance is related to disease activity.
Figure 4 Fcy receptor imbalance exists in monocytes of BD patients.
In addition, there are also abnormalities in BD monocyte subpopulations.
IM increases and NCM decreases.
These two are also closely related to the disease activity of BD.
Figure 5 Abnormality of BD monocyte subpopulations.
In addition, BD-CM and IM secrete pro-inflammatory cytokines increased, and BD-CM promotes Th1 differentiation.
Progress 2: BD has the same inflammation path as autoinflammatory diseases, and the clinical features overlap each other.
1 Clinical manifestations, men and women are "different", 40 years old is a "division line" The clinical features of BD and hereditary autoinflammatory diseases overlap each other.
It can be manifested as mucosal ulcers, joint disease, and uveitis.
In addition, the inflammation recurred and relieved repeatedly, and there was no obvious triggering factor for the attack.
Last year, a study by Professor Zheng Wenjie and others showed that the male to female ratio of BD patients in my country was about 1.
41, with a median age of 34 years.
Male patients often present with ophthalmitis, vascular involvement, pseudofolliculitis, and acupuncture reactions; female patients have more common genital ulcers.
Vascular lesions and gastrointestinal ulcers are common in patients over 40 years old, while pseudofolliculitis and acne-like rash are common in patients under 40 years old.
2 Involvement of large vessels accounts for "half of the cause of death" Among the main causes of death in BD patients in my country, the main cause of involvement of large vessels (54.
2%), including ruptured aneurysms, venous thrombosis/occlusion, and severe valve disease.
Figure 6 The main cause of death of BD patients in my country is very important due to the involvement of large blood vessels in BD, and it has also been included in the 2014 new International Standards for Behcet's Disease (ICBD).
BD complicated with heart valve disease has an insidious onset, lack of specificity in cardiac performance, with moderate/severe aortic insufficiency (ascending aortic dilation or aneurysm, valve prolapse, neoplastic formation, valve perforation or tear, and paravalvular abscess ) Mainly, less involving the mitral and tricuspid valves.
The risk of postoperative complications of BD combined with valvular disease is extremely high (49.
2%-100%), mainly including repeated paravalvular leaks and anastomotic aneurysms.
After complications occur, the mortality rate is as high as 60%, and the risk of reoperation is as high as 30%-90%.
Studies have also shown that the control of the primary disease in the perioperative period is closely related to the incidence of complications such as postoperative paravalvular leakage.
All of these conditions can increase the risk of postoperative paravalvular leaks and other complications: no immunosuppressive agents were used before surgery; preoperative CTX accumulation was low; preoperative erythrocyte sedimentation rate (ESR) was significantly increased; no postoperative use Immunosuppressive agent.
Progress 3: Progress in BD drug treatment 1 What is the effect of interferon on BD uveitis? According to the latest EULAR guidelines for clinical management of Behçet’s syndrome in 2018, TNF-α inhibitors are drugs with a higher level of evidence for the treatment of BD.
However, there are also some contraindications for the monoclonal antibody TNF-α, such as recurrence of tuberculosis, Combined with HBV infection and so on. This requires researchers to focus on drugs other than TNF-α inhibitors.
In 2019, Professor Wenjie Zheng published a study on the use of interferon combined with hormone immunosuppressants to treat refractory BD uveitis.
Figure 7 In 2019, Professor Wenjie Zheng published a study on Therapeutic Advances in Chronic Disease.
This study is the first domestic and foreign research report on the use of IFNα-2a combined with hormones and immunosuppressive agents for refractory BD uveitis, and proves this The therapy is safe, effective and inexpensive.
Professor Zheng Wenjie believes that this therapy can be recommended as the first-line treatment for refractory BD uveitis in the Chinese population.
2secukinumab anti-interleukin-17A monoclonal antibody In 2020, a multi-center study on the long-term effectiveness and safety of secukinumab (an IL-17A monoclonal antibody) on refractory mucosa and joint BD was published in Ann Rheum On Dis.
Figure 8 The study published in Ann Rheum Dis in 2020.
The study believes that the treatment of secukinumab 300mg/m has certain benefits for oral ulcers and arthritis, as well as scrotal ulcers, axial arthritis and intestinal lesions.
beneficial.
3MAGIC syndrome, which biologics is better? The syndrome in which BD and recurrent polychondritis (RP) coexist is called MAGIC syndrome.
For this part of patients, Professor Zheng Wenjie found through research that infliximab (IFX) is effective, while tocilizumab (TCZ) The curative effect is not satisfactory.
Summary: In recent years, the research on BD has made fruitful progress from the molecular level to the clinical treatment.
As the core force in the field of rheumatology and immunology in my country, the team led by Professor Zheng Wenjie has made outstanding contributions to the research of BD.
At this conference, Professor Zheng Wenjie Luo listed many outstanding recent achievements, such as innate immunity is very important in the occurrence and development of BD, especially the excessive activation and infiltration of neutrophils; and monocyte Fcy receptors The imbalance is related to the activity of the disease.
BD has the same inflammation path as autoinflammatory diseases, and the clinical features overlap with each other.
Large vessel involvement is the main cause of death in BD patients in my country, while heart valve disease has an insidious onset, but the risk of postoperative complications is extremely high (49.
2%-100 %), and the mortality rate after complications is as high as 60%.
On the treatment level, Professor Zheng Wenjie recommended interferon combined with hormones and immunosuppressants as the first-line treatment for refractory BD uveitis in the Chinese population.
Looking forward to more outstanding achievements in 2021.
