If the antibody is positive and there are symptoms, it must be lupus that "meets the diagnostic criteria"?

*It is only for medical professionals to read for reference.
Prevention is the last word! The 23rd Asia-Pacific Rheumatism Alliance (APLAR) Online Conference was successfully held in Kyoto, Japan from August 28 to 31, 2021.
Professor David Karp from the Southwestern Medical Center in the United States brought you "Understanding Preclinical Immunity Status—— Can we prevent systemic lupus erythematosus" special report
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As we all know, the prognosis of the disease is closely related to regular screening and strict preventive measures.
For example, strict control of high blood pressure can prevent cardiovascular and cerebrovascular accidents, and injection of the new crown vaccine can prevent COVID-19 virus infection
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So is it possible to prevent rheumatism with some measures? How to assess our risk of rheumatism? How should we target treatment? Professor Karp put forward his own unique insights in response to the above problems
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Incomplete lupus erythematosus: Where is the incompleteness? Professor Karp introduced that there are only a small number of people at high risk of systemic lupus erythematosus (SLE) in the world, and related risk factors include genetics, sun exposure, metabolic abnormalities, and diet
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After the onset of SLE, the first thing that changes is the state of the immune system, such as anti-nuclear antibody (ANA), anti-SSA (Ro) antibody, anti-SSB (La) antibody, various cytokines and chemical factors, and B cell gene expression The change of EBV and the reactivation of monocytes to Epstein-Barr virus (EBV) are involved
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Then there will be some non-specific SLE symptoms, such as leukopenia, decreased platelets, decreased levels of complement C3 and C4, scattered skin erythema and joint swelling
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This stage can also be called "Incomplete Lupus Erythematosus" (Incomplete Lupus Erythematosus, the preclinical stage of lupus, ILE), which is the preclinical stage before the onset of SLE, which is characterized by the expression of autoantibodies and non-specific clinical symptoms
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If the patient fails to see a doctor in time during this period, subsequent irreversible tissue damage may occur
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Figure 1 ILE standards and main clinical manifestations.
Knowing yourself and the enemy can help you survive.
In summary, the window period for early detection and prevention of SLE is the period when the immune system changes and symptoms appear
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So, what are the early characteristics of changes in the immune system? How many patients will have typical SLE manifestations? Can we reverse the changes in the immune system and bring it back to normal? ■ ANA-related gene testing can screen high-risk populations for SLE.
A large number of retrospective studies and cohort studies have found that "preclinical immune status" is very common in the population, and 8% of healthy people will also be ANA positive
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Gene sequencing results showed that in 773 SLE patients and 579 control groups, there were approximately 125,000 mutation sites, and most of these mutations affected gene expression rather than protein structure
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The researchers conducted the test simultaneously on healthy people who were ANA-positive, and the results showed that some gene mutation sites in SLE patients also existed in this part of the healthy people
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This indicates that there is a certain "grey area" between gene locus changes and the occurrence of diseases.
The use of ANA-related gene testing can greatly help us early detection and screening of people at high risk of SLE
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Table 1 Comparison of gene mutation sites between ANA-positive healthy people and SLE patients ■ Immune system changes precede clinical symptoms.
The production of autoantibodies is also an important part of immune system changes.
Common autoantibodies in rheumatism include ANA, anti-SSA antibodies, and SSB antibodies, anti-dsDNA antibodies
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A survey of SLE patients from the US military was published on NEJM.
88% of patients had at least one autoantibody positive before the diagnosis, and the appearance of autoantibodies was 9.
4 years earlier than the diagnosis on average
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In addition, Professor Karp also introduced his team's experiment using UT Southwestern autoantigen gene chip to screen autoantibody titers in different populations (healthy ANA-, healthy ANA+, ILE and SLE).
The results showed that with ANA expression As the disease progresses, more autoantibodies are produced; before the diagnosis of SLE, the expression of many cytokines is also on the rise
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All in all, changes in the immune system precede clinical symptoms, so we can predict the occurrence of SLE by detecting regulatory factors such as autoantibodies and interferons
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Figure 2 Using autoantibodies and interferon to predict SLE Since the incidence of SLE is not very high, screening tests need to be as specific as possible
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Obviously, ANA cannot be used as an independent factor to assess the risk of SLE.
It also needs to be jointly assisted based on genetic risk factors, other autoantibodies, cytokines and other related tests
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Professor Karp pointed out that most of the previous data are retrospective, and we need more prospective randomized trials to confirm the feasibility of SLE risk assessment
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■ 2%~5% of ILE patients are transformed into SLE, so how to judge whether a patient is changing from "preclinical stage" to "clinical stage"? Faced with this problem, observing healthy people is obviously inefficient and cost-effective work
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It is the most preferable to evaluate through gene-related testing, but it cannot be popularized in clinical practice at present, and it can only be judged by observing whether it meets the standard of ILE
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In a cohort study of ILE, it was also pointed out that age, American College of Rheumatology (ACR) classification criteria, and SLE disease activity score (SLEDAI) were statistically different between ILE and SLE patients.

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After reading previous related literature, Professor Karp believes that 2% to 5% of ILE patients will become SLE every year
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At the same time, Professor Karp also pointed out the current problems
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One is that there is no internationally recognized definition of ILE; the other is that there is no detection method that can accurately screen the autoantibodies and cytokines that are closely related to the onset of SLE
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How should we prevent SLE? Hydroxychloroquine is widely used in the treatment of SLE based on long-term experience and very good safety
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A retrospective cohort study showed that early use of hydroxychloroquine can delay the onset of SLE by at least one year
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At the same time, research results show that the use of hydroxychloroquine to treat ILE patients can reduce the expression of IFN-related genes
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To prove and quantify the role of hydroxychloroquine in the preclinical stage of SLE
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Professor Karp introduced a prospective randomized controlled trial (RCT) study that hypothesizes that early use of hydroxychloroquine can prevent the accumulation of clinical abnormalities and change the immune response of SLE
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The study randomized ILE patients [ANA titer> 1:80, and met one or two additional criteria in the 2012 Systemic Lupus International Cooperative Clinic (SLICC) classification criteria] randomized to hydroxychloroquine and placebo
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The age range is 15-45 years old, and the treatment period is 96 weeks
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The primary endpoint is the increase in the number of SLE patients who meet the 2012 SLICC classification criteria
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The study will evaluate whether hydroxychloroquine can be used to measure the progress of SLE by accumulating criteria.
It will also investigate candidate biomarkers that guide treatment decisions and accumulate a sample biobank for further research in the SLE research community.

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Summary: In the end, Professor Karp gave his insights on two key questions: 1.
When should we start screening for the risk of SLE? Answer: Screening should be started earlier (15-40 years old), and screening every 3~5 years
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2.
How should I screen for SLE? A: comprehensive diagnosis by including ANA, anti-ENA and other autoantibodies and cytokines
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In terms of screening population delineation and treatment options, the existing research results are still unable to provide us with more evidence.
Professor Karp hopes that more convincing long-term data can give us answers in the future
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Experts comment that SLE is one of the most representative rheumatoid diseases.
It has multiple organ involvement, complex conditions, difficult diagnosis and treatment, and high mortality.
It is a major chronic disease that seriously threatens the health of our people, especially young women
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The specific pathogenesis is unclear, and genetic, environmental, metabolic and infectious factors are involved
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Of course, how to identify and intervene early to avoid irreversible organ damage is the current international and domestic difficulties and challenges in the prevention and treatment of SLE, especially for patients with incomplete lupus in the "pre-clinical state", rheumatologists should pay more attention , Implement more active screening methods and follow-up strategies
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Professor Karp's research has provided us with the most advanced concepts and updated information, but as it summarizes, it still needs to be confirmed by further high-quality clinical studies
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As an area with a high incidence of SLE, China has a large number of patients.
It should be actively explored in this regard.
Eventually, SLE will be strangled in the bud, and SLE may be "eliminated" or "cured" in the near future.
I look forward to such a beautiful day
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 Expert Profile: Associate Professor Zhao Jiuliang, Associate Professor, Assistant Director, and Doctor of Medicine, Department of Rheumatology and Immunology, Peking Union Medical College Hospital.
Mainly engaged in basic and clinical research on systemic lupus erythematosus, antiphospholipid syndrome, connective tissue disease-related pulmonary hypertension and other rheumatic immune diseases
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Participated successively in the national "Eleventh Five-Year Plan", "Twelfth Five-Year Plan", and "Thirteenth Five-Year Plan" related topics related to systemic lupus erythematosus
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He has spoken 13 times at national academic conferences and 9 international conferences on behalf of the team, and published more than 60 core journal articles at home and abroad, including 13 SCI papers as the first author and corresponding author, and won the International Youth Award of the Japanese Academy of Rheumatology and East Asian Rheumatology.
Youth Award of the Chinese Academy of Diseases, Travel Award of the International Lupus Congress, Outstanding Paper Award of the Chinese Society of Rheumatology, and the 2nd Association of Outstanding Youth Award.
Currently serving as Deputy Chairman of the Youth Committee of the Asia-Pacific Association of Rheumatology (APLAR), Department of Rheumatology and Immunology, Chinese Medical Association Deputy Chairman of the Youth Committee of the Physician Branch, member and secretary of the Rheumatology Branch of the Beijing Medical Association, member of the Standing Committee of the Rheumatology and Immunology Professional Committee of the Cross-Strait Medical and Health Exchange Association, and young editorial board member of "Peking Union Medical College" and "Chinese Journal of Clinical Immunity and Allergy" Source of this article: Medical Rheumatism Channel Author of this article: Bi Yuanyun Review of this article: Associate Professor Zhao Jiuliang Editor in charge of Peking Union Medical College Hospital: Cassette copyright declaration Reliable, but does not make any promises or guarantees regarding the timeliness of the published content, as well as the accuracy and completeness of the cited information (if any), and does not assume that the content is out of date and the cited information may be inaccurate any liability or incomplete and so caused
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Relevant parties are requested to check separately when adopting or using this as a basis for decision-making
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