Don't want to develop rheumatoid arthritis, it's right to pay attention to this antibody!

*Only for medical professionals' reference.
In the first few years before the onset of typical symptoms of RA, patients have already produced autoantibodies in their bodies
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 Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that is mediated by cytokines and is characterized by symmetrical joint swelling and pain of the extremities.
If not treated in time, it will cause stiffness and deformity of the affected joints.
And loss of function seriously affects the patient’s quality of life
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It is worth noting that a few years before the onset of typical symptoms of RA, patients have already produced autoantibodies, and the discovery of RA-related autoantibodies makes early diagnosis and early treatment of RA a reality
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In the 13th "Rheumatoid Arthritis International Forum", Professor Zhao Jinxia from Peking University Third Hospital gave a wonderful report on "early diagnosis of preclinical rheumatoid arthritis"
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Preclinical RA includes 5 stages.
Professor Zhao Jinxia introduced that individuals at risk of RA before the onset, that is, preclinical, mainly include the following stages: RA risk individuals based on genetic and environmental risk factors, no laboratory abnormalities and inflammatory conditions Symptoms or signs of arthritis; based on laboratory abnormalities (such as ACPA, RF positive), individuals at risk of RA without symptoms or signs of inflammatory arthritis; based on symptoms of inflammatory arthritis (such as arthralgia/morning stiffness) Individuals at risk of RA have no clinical or imaging evidence of synovitis; imaging shows synovitis, but there is no clinically obvious inflammatory arthritis; clinically obvious inflammatory arthritis has not yet reached the RA classification criteria
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Among them, autoantibodies have important direct and indirect pathogenic effects in the occurrence and development of RA
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Direct pathogenic effect means that autoantibodies bind to functional autoantigens expressed in target organs to directly inhibit or induce their functions
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The indirect effect refers to that immune complexes induced by autoantibodies activate inflammatory mediators or the complement system through FcγR, resulting in systemic or local tissue damage
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Anti-citrullinated protein antibody (ACPA) occupies a very important position in the development of RA
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In the progression of RA, humoral immunity against citrullinated self-antigens can be triggered by environmental factors at the mucosal site, and then individuals carrying ACPA can remain disease-free for a long time, which indicates that the initial antibody library cannot obviously trigger the pathogenesis of disease
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The ACPA library can eventually target key cell signaling molecules through the evolution of somatic hypermutation and antigen-driven selection
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Therefore, ACPA may have triggered certain pathogenic signals before the onset of the disease, such as pain and bone erosion, and promoted the development of arthritis under the "second blow".
Therefore, the onset of RA is related to the increase in ACPA levels and the further increase in antibody diversity.
Expansion related
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At present, there have been many relevant research results on the pathogenic effects of ACPA.
The main pathogenic effects that have been teased out include: (1) macrophage activation; (2) promotion of osteoclast activation and bone loss; (3) ) Regulate synovial fibroblasts; (4) Induces new type of programmed cell death (NETosis) and the formation of NET-derived immune complexes; (5) Induces pain; (6) Other effects: activates mast cells, promotes complement activation, Activate platelets
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Professor Zhao Jinxia compared the similarities and differences of early arthritis symptoms between ACPA-positive and negative patients.
She said that ACPA-positive patients are more likely to have both upper and lower limbs, while ACPA-negative patients are less likely to have lower limbs.
However, both types of patients There is almost no difference in joint pain and joint swelling
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So from the phenotype of RA in the preclinical stage, are there similarities and differences between APCA-positive and negative patients? Professor Zhao Jinxia gave a detailed account for everyone through a cohort study
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This is a study of patients who eventually developed arthritis in a cohort of patients with clinically suspected joint pain at the Leiden Center (n=67)
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The study compared the symptoms and signs of arthralgia in ACPA-positive and negative patients at the onset of symptoms, and the time to develop arthritis, and found the clinical differences between the two types of patients in the symptom phase, further explaining the possibility of the development of RA in the two types of patients It's different
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Figure: How can the clinical differences between the two types of patients in the symptom phase accurately predict and identify preclinical RA patients at an early stage? Professor Zhao Jinxia first introduced in detail the early RA (ERA) classification and diagnostic criteria that are particularly suitable for clinical applications, mainly including: (1) Morning stiffness ≥30 minutes; (2) Polyarthritis: at least 3 of the 14 joint areas (3) Hand arthritis: at least 1 joint swelling of wrist, palm finger or proximal interphalangeal joint; (4) RF positive; (5) anti-CCP antibody positive
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The above conditions can be diagnosed with more than 3 items
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In 2017, the European Union Against Rheumatism (EULAR) aims to define new clinical parameters describing CSA by defining the clinical characteristics of patients with clinically suspected arthralgia (CSA), as follows: The history of the recent joint symptoms that occurred, less than 1 year ; Metacarpophalangeal joint (MCP) symptoms; morning stiffness lasts longer than 60 minutes; more severe symptoms appear in the morning; first-degree relatives of RA patients
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Physical examination: Difficulty in making a fist; the metacarpophalangeal joint squeeze test is positive
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Professor Zhao Jinxia said that the above two diagnostic criteria mentioned the concept of "morning stiffness" (MS), so what is the correlation between MS and subclinical arthritis in CSA patients? A laboratory examination and hand-foot MRI examination of 575 patients with CSA found that compared with patients without MS, patients with MS more frequently developed subclinical synovitis, subclinical tenosynovitis, and elevated CRP
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In patients whose CSA develops into RA, MS is more closely related to subclinical synovitis and CRP, and the correlation increases with the duration of MS
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In addition to MS, ACPA is still an important factor predicting the development of RA
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Professor Zhao Jinxia said that studies on ACPA-positive individuals showed that the development rate of RA was 40%-60% during a follow-up period of 2-5 years
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In addition, other factors that affect the development of RA should not be omitted, including: RF positive, joint pain and tenderness, smoking, obesity, and imaging development of subclinical arthritis
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Nowadays, many new markers of RA are in full swing, such as Scavenger Receptor A (SR-A)
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This is a pattern recognition receptor, which is mainly expressed on myeloid cells.
Its sensitivity in RA is 66.
41%, which can be used as one of the markers of early RA
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Professor Zhao Jinxia believes that the combined application of multiple antibodies may be more helpful in identifying individuals at high risk of RA patients, such as the combined use of ACPA, RF, and anti-carbamylated protein (CarP) antibodies
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In addition to RA markers, imaging is also an important RA detection method
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High-resolution peripheral quantitative computed tomography (HR-PQCT) is an emerging imaging technology in recent years.
It can qualitatively and quantitatively measure the three-dimensional microstructure and volumetric bone mineral density of trabecular bone in the body, with extremely high accuracy and relative accuracy.
Low-dose radiation
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In addition, MRI is also an important method to detect early joint inflammation, so the combined detection results of HR-PQCT and MRI for the early diagnosis of RA are naturally more accurate
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Professor Zhao Jinxia also mentioned that in addition to synovitis, tenosynovitis is also an early feature of RA and is an independent predictor of the development of RA in patients with CSA and UA
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Where is the future research road for the diagnosis and treatment of preclinical RA? In this regard, Professor Zhao Jinxia believes that in the future, we will continue to develop and verify new clinical indicators and biomarkers, and at the same time formulate an accurate prediction model that evolves from preclinical rheumatoid arthritis (Pre-RA) and CSA to RA
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It is still controversial whether to give specific treatment to pre-RA patients who are at high risk of developing RA
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However, there is no doubt that in the clinical diagnosis and treatment of RA patients, it is necessary to determine targeted interventions to promote antigen-specific tolerance, so as to intervene in the continuous extra-articular immune changes that occur in the preclinical stage, and bring more changes to the patients.
Good treatment effect
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