Professor Li Xiaofeng: New exploration in the treatment of AID, combining biological agents with non-drug therapy on the basis of conventional treatment

It is only for medical professionals to read and refer to clinical treatment plans for autoimmune diseases.
Experts have something to say that autoimmune diseases (AID) are a type of diseases in which the body attacks its own tissues due to abnormal immune system function.
There are many kinds of diseases.
Common diseases include rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and vasculitis
.

Many rheumatic diseases belong to AID.
Most of them have complicated causes, diverse clinical manifestations and pathological changes, involving multiple organs and multiple systems, and are highly heterogeneous
.

How to treat AID is a clinical medical problem that we have been diligently seeking.
In this issue, we invited Professor Li Xiaofeng from the Second Hospital of Shanxi Medical University to talk about his views and insights
.

 For the treatment of rheumatic diseases, especially AID, Professor Li Xiaofeng mentioned that the application of biologics is a milestone progress, and they provide doctors with The powerful treatment weapon has greatly improved the treatment level of many diseases and changed the previous treatment pattern
.

Targeted therapy led by biological agents is mainly targeted at a key mechanism or target in the development of the disease, such as important inflammatory factors involved in immune inflammatory response, signal transduction pathways or immune effector cells
.

Professor Li Xiaofeng pointed out that biological agents tend to take effect quickly, can quickly control inflammation and induce disease remission, which is a very effective treatment option in the acute phase
.

When talking about the safety of biological preparations, Professor Li Xiaofeng believes that compared with traditional therapeutic drugs (such as immunosuppressants), biological preparations selectively inhibit a certain target and have less impact on the body's normal immune response in the short term
.

After the patient's condition is stable, biological agents can be stopped as appropriate to control the occurrence of adverse reactions.
For patients who need to use biological agents for a long time, try to choose biological agents with relatively good safety
.

"We must correctly understand the mechanism of action of biological agents and grasp their therapeutic status
.
As
the so-called'good steel is used on the blade', the application of appropriate biological agents at the right time can help patients quickly and effectively control their disease
.

" Professor Li Xiaofeng said
.

 How to prescribe the right medicine, how to maximize the effectiveness of biological agents and achieve a balance between benefits and risks? There are many types of biological agents.
According to different targets and mechanisms, they can be roughly divided into the following categories: tumor necrosis factor-α (TNF-α) inhibitors, interleukins (such as IL-6, IL-17) inhibitors agents and biological agents (e.
g.
, rituximab, Beili You mAb) targeting B lymphocytes and T-lymphocytes targeted biologies (e.
g.
, abatacept) and the like
.

Various biological agents have very different effects in different types of diseases
.

Professor Li Xiaofeng pointed out that according to the type of immune response of different diseases, biological agents with different mechanisms of action should be selected for highly matched treatment
.

Professor Li Xiaofeng took SLE as an example to introduce the characteristics of its immune response and the choice of therapeutic drugs
.

SLE is a complex and multi-system AID.
In view of the core role of autoantibodies and autoreactive B cells in its pathogenesis, the biological agent beliyuumab targeting B lymphocyte stimulating factor (BLyS) It has played a good role in the treatment of SLE [1-2]
.

In addition, the abnormalities of T cells and their signal transduction, especially the imbalance between helper T cells 17 (Th17) and regulatory T cells (Treg), have also been related to the development of SLE [3]
.

Professor Li Xiaofeng introduced that Th17 cells mainly mediate tissue inflammation and continue the destruction process; while Treg cells fight inflammation and maintain immune tolerance.
Under normal conditions, the two maintain a balance
.

However, in clinical testing, an increase in the number of Th17 cells in SLE patients is often observed, while the number of Treg cells is significantly reduced or their function is impaired.
The balance between the two is imbalanced, which leads to the immune dysfunction [3-4]
.

Therefore, targeting costimulatory or adhesion receptors on T cells may be another treatment option for SLE
.

Figure 1: The balance of Treg cells and Th17 cells in SLE patients is unbalanced [3] (The increase in the left side of the balance represents a decrease in the number of Tregs, and the decrease on the right represents an increase in the number of Th17 cells; the red arrow indicates the relative transcription factor or cytokine in SLE patients Change in expression) Abatacept is a T cell costimulatory signal regulator, which can inhibit T cell activation induced by autoantigens by competing with CD28 to bind to CD80/CD86
.

Professor Li Xiaofeng pointed out that according to the mechanism of action of abatacept, it is suitable for the treatment of the acute phase of SLE and is conducive to the rapid control of patient symptoms
.

At the same time, he introduced to us the experience of using abatacept in the treatment of SLE: a case of SLE patients treated with conventional immunosuppressants, the condition is difficult to control, the erythrocyte sedimentation rate is still elevated, and the level of urine protein remains high (++++)
.

After the addition of abatacept treatment, the patient not only returned to normal indicators and significantly reduced urine protein, but also reduced the original hormone and immunosuppressant dosage.
This fully reflects the remission induction effect of abatacept in the acute phase of the disease, and It proves the importance of the fit between the mechanism of action of the drug and the pathological mechanism of the disease to the clinical efficacy
.

In addition, Professor Li Xiaofeng also pointed out that safety is the first priority for rational drug use
.

Although biological agents have significant efficacy, there are still certain safety risks in long-term use
.

"The body's immune system has two very important functions, one is to prevent and fight infection; the other is immune surveillance
.

Biological agents block certain key links in the immune system, which may interfere with the normal immune function, thereby increasing The risk of infection or tumor occurrence
.

” Professor Li Xiaofeng pointed out, “After the patient’s condition is relieved and stabilized, biological agents can be stopped as appropriate to avoid the safety risks caused by their long-term use
.

If biological agents are used for a long time, they must pay attention to regular monitoring.
, Including tuberculosis, hepatitis B virus infection and tumor occurrence
.

"In the above cases of abatacept in the treatment of SLE, Professor Li Xiaofeng did not observe obvious adverse reactions, and previous research data also showed that abatacept is in The safety risks in related fields are low (such as tuberculosis, hepatitis B infection risk) [5-11], indicating that its safety is good
.

 Regulating the immune microecological balance is helpful to the sustained remission of the disease.
Due to the complex etiology, the exact pathogenesis of most AIDs is not yet clear and cannot be cured.
The treatment goals are mainly the long-term remission of the disease and the improvement of the quality of life of patients
.

Professor Li Xiaofeng specifically mentioned the topic of "immune microecology"
.

"The body's microecology and immune function are closely related
.

In recent years, more and more studies have found that the imbalance of the intestinal microecology can lead to abnormal functions of the body's immune system, and further trigger the occurrence and development of AID
.

" The intestine is the body's largest "immunity" Organ”, whose flora disorder is one of the key factors in the pathogenesis of AID, can mediate the over-activation of autoreactive T cells and the defect of self-tissue tolerance [12-13]
.

"We may be able to think about the occurrence, development and transformation of AID from this perspective, and adjust and improve our life>
.

"Professor Li Xiaofeng mentioned, "Adjust the activity of intestinal flora through life>
.

"Summary: AID is a series of chronic inflammatory reactions caused by imbalance of immune tolerance, which can cause damage to the body's own tissues
.

Its incidence is increasing year by year, but the pathogenesis is still unclear
.

Biological agents have been used in the field of AID treatment in recent years .
Innovative drugs widely used in China, are conducive to the rapid control of disease symptoms, alleviation of the disease, and significant effects
.
In-
depth understanding of the mechanism of action, treatment status and related risks of various biological agents is essential for the outcome of disease treatment
.

In addition, regulation and Improving life>
.

 Expert profile Professor Li Xiaofeng, chief subject leader, professor, doctoral tutor, and postdoctoral tutor of the Second Hospital of Shanxi Medical University enjoys special government allowances from the State Council, winner of the May 1st Labor Medal of Shanxi Province, and won the first National Famous Doctors Summit Forum "National Famous Doctors-Excellent Achievement" "Title and Shanxi Famous Doctor Title: Standing Committee Member, Chinese Medical Association Rheumatology Association, Vice President, Chinese Medical Association Rheumatology Branch, Chinese Medical Association Shanxi Branch Director, Chinese Medical Association Shanxi Branch Rheumatology Professional Committee Chairman, Cross-Strait Medical Exchange Health Association Rheumatology Vice Chairman of the Expert Committee, Chairman of the Infectology Group Vice Chairman of the Chinese Rheumatology Medical Association Vice Chairman of the Shanxi Medical Association Standing Committee Member of the Rheumatology Branch Chairman of the Shanxi Regional Alliance Chairman of the Chinese Journal of Rheumatology and Chinese Journal of Allergy Editors and other reference materials: [1] Choi J, Kim ST, Craft J.
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Curr Opin Immunol,2012,24(6):651-7.
[2]Song Hui.
The timing of using biologics in patients with lupus erythematosus: facts and controversies[J].
Chinese Journal of Clinicians,2015,43(7):13-16.
[3]Rother N,van der Vlag J.
Disturbed T Cell Signaling and Altered Th17 and Regulatory T Cell Subsets in the Pathogenesis of Systemic Lupus Erythematosus[J].
Front Immunol,2015,6:610.
[4]Moulton VR,Suarez-Fueyo A,Meidan E,et al.
Pathogenesis of Human Systemic Lupus Erythematosus:A Cellular Perspective[J].
Trends Mol Med,2017,23(7):615-635.
[5]Westhovens R,Robles M,Ximenes AC,et al.
Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors[J].
Ann Rheum Dis,2009,68(12):1870-7.
[6]Bathon J,Robles M,Ximenes AC, et al.
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[7]Weinblatt ME,Schiff M,Valente R,et al.
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Arthritis Rheum,2013 ,65(1):28-38.
[8]Schiff M,Weinblatt ME,Valente R,et al.
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Ann Rheum Dis,2014,73(1):86-94.
[9]Genovese MC,Schiff M,Luggen M,et al.
Longterm safety and efficacy of abatacept through 5 years of treatment in patients with rheumatoid arthritis and an inadequate response to tumor necrosis factor inhibitor therapy[J].
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[10]Padovan M, Filippini M,Tincani A, et al.
Safety of Abatacept in Rheumatoid Arthritis With Serologic Evidence of Past or Present Hepatitis B Virus Infection[J].
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[11]Kim PS,Ho GY ,Prete PE,Furst DE.
Safety and efficacy of abatacept in eight rheumatoid arthritis patients with chronic hepatitis B[J].
Arthritis Care Res(Hoboken),2012,64(8):1265-8.
[12]Cheng Ting, Li Xiaofeng , Niu Hongqing, et al.
Progress in research on intestinal flora regulating T cell immunity and participating in the pathogenesis of autoimmune diseases[J].
Chinese Journal of Rheumatology,2020,24(7):484-488.
[13]Guo Fengyi, Yang Xiao, Gao Tianshu.
Research progress of intestinal flora in autoimmune diseases[J].
Journal of International Immunology,2021,44(1):91-96.
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