The weather vane of rheumatic immune disease-there are so many ways for biomarkers...

*Only for medical professionals to read and clarify this relationship, the condition is a thread~ For the diagnosis and condition monitoring of rheumatism, various biomarkers are very important
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Different biomarkers are used as weather vanes for different rheumatoid diseases.
Many people have spent a lot of energy just remembering their clinical significance.
Have you ever thought before the screen: There are also thousands of different biomarkers for rheumatoid diseases.
Links? At the 13th International Forum on Rheumatoid Arthritis (IFRA), Professor David S.
Pisetsky from Duke University summarized the complex "fate" between biomarkers for everyone
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Crucial: Biomarkers are of great significance to rheumatism and immune diseases.
In the diagnosis of rheumatism and immune diseases, the functions of biomarkers can be described as rich.
Disease risk factors, pay attention to the patient’s subclinical manifestations during the disease screening stage, clarify the diagnosis of the disease, classify the development stage of the disease when assessing the degree of disease activity, predict the prognosis of the disease, supplement the diagnosis, and guide the treatment of the disease
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For systems such as systemic lupus erythematosus (SLE), Sjogren’s syndrome (SS), systemic sclerosis (SSc) or myositis, the clinical significance of biomarkers is naturally needless to say
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Taking rheumatoid arthritis (RA) related research as an example, researchers continue to discover new biomarkers to identify seronegative patients, predict prognosis, guide treatment, and establish treatment goals.
It can also be used to improve disease resistance.
Rheumatism drugs (DMARDs) reference for stopping and stopping
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The level of biomarkers in RA patients can be affected by multiple systems, which are closely related to the characteristics of the disease itself.
The types include anti-nuclear antibodies, interferons, immune complexes, and complement activators
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Many autoantibodies have different specificities and sensitivities for different autoimmune diseases.
This determines that different autoantibody profiles can determine a certain type of autoimmune disease.
For example, doctors often pay more attention to the anti-cycloquinone of RA patients.
Anti-CCP (anti-CCP), rheumatoid factor (RF), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and anti-nuclear antibodies (ANA) and anti-DNA should be paid more attention to patients with SLE antibody (anti-DNA), anti-retinol binding protein antibody (anti-RBP), complement and interferon
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So, is there a biomarker that has significant clinical significance for both RA and SLE? Seek common ground while reserving differences: The expression forms of biomarkers for different autoimmune diseases are indeed different.
Knowing what they are is best to know why.
Although today we know that the expression of biomarkers for different immune diseases is different, the story behind this is It took several generations of researchers' hardships to understand it slowly
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As early as 1971, some researchers pointed out that there was no inevitable connection between RA patients and increased complement levels [1].
Then in 1982, researchers found that some tests have limited significance for RA disease assessment, while some tests are not RA has good predictive value for extra-articular and vascular involvement [2]
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In the years that followed, researchers continued to find that biomarkers such as anti-CCP antibodies and immune complexes have significant clinical significance for RA disease [3-5], while markers such as complement have more clinical significance for SLE disease.
Obviously [6]
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So far, it has been found that the expression profiles of biomarkers of different rheumatic immune diseases do have a certain rule of "reserving differences"
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So, can we "seeking common ground"? A 2007 study found that some characteristics of interferon can distinguish unique subgroups in RA patients, which are characterized by increased immune system activity, decreased blood coagulation and complement levels, and abnormal lipid metabolism [7]
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With continuous in-depth research, people have discovered that there is a real possibility of "seeking common ground": A study pointed out that type I interferon (IFN) pathways exist in 5 rheumatic immune diseases including SLE, RA, SSc, etc.
The activated state [8], even boldly predicting that these diseases can benefit from anti-IFN treatment! Then in 2010, two successive studies by the same research team found that the effects of interferon on the immune function of RA patients were inconsistent, so it is inferred that the expression of biomarkers in different RA patients is different [9-10], Later research undoubtedly made people more and more fascinated by the link between biomarkers and rheumatic immune diseases: RA patients using certain types of biological agents would actually produce lupus-like autoantibodies due to the increased levels of lupus-related cytokines [11] This study also coincides with the conclusion of another study 11 years ago: it is not only a certain type of biological agent that can induce the production of lupus-like antibodies, and it is not only the biological treatment of RA, which is a disease.
This inducing effect can be subtracted after the treatment of related biological agents is over.
It needs to be clear that this inducing effect is related to ANA, and this effect has nothing to do with the clinically seen lupus-like symptoms, but it is related to use For non-lupus patients with biological agents, it is still necessary to monitor the development of lupus-like symptoms [12]
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Get to the bottom of the question: The mystery of seeking common ground while reserving differences actually depends on this root cause.
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Researchers have spent decades clearing away the fog step by step, and finally found that the difference in biomarker spectrum of different rheumatic immune diseases is most fundamentally related to the physiological and pathological process of the disease itself.
Closely related
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Taking SLE as an example, the patient's immune complexes can mimic the receptors of nucleic acids, and thus produce type I IFN, which fundamentally leads to differences in the expression of biomarkers between it and RA patients
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Researchers have found that the level of anti-DNA antibodies is negatively correlated with complement, and the immune complexes produced by anti-DNA antibodies will stimulate the production of IFN.
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After the researchers have successively proved the internal connection between different autoantibodies, It is found that this is the fundamental reason for the regular differences in the biomarker profiles or autoantibody profiles of patients with different rheumatoid diseases
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Summary: Professor David S.
Pisetsky’s sharing took RA and SLE as examples, and explained that the expression of antinuclear antibodies in the two rheumatoid immune diseases is different, and there is a "seeking common ground while reserving differences" posture: Although RA and SLE can have ANA, but The expression of anti-CCP antibody in RA patients is more significant, while the level of complement in SLE changes more significantly
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The root cause of this difference is closely related to the pathophysiological manifestations of the disease itself.
For example, the expression of anti-DNA in SLE patients is inherently related to complement activation
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At the same time, the professor pointed out that this situation of seeking common ground while reserving differences may also mean that some current biomarkers need to be cautious about their clinical significance.
For example, IFN that is significantly expressed in SLE patients may also appear in specific types of RA.
This is also for the future The research provided some feasible directions
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References: [1]Franco AE,Schur P H.
Hypocomplementemia in rheumatoid arthritis[J].
Arthritis&Rheumatism,1971,14(2):231-238.
[2]McDougal JS,Hubbard M,Mcduffie FC,et al.
Comparison of five assays for immune complexes in the rheumatic diseases.
An assessment of their validity for rheumatoid arthritis[J].
Arthritis&Rheumatism:Official Journal of the American College of Rheumatology,1982,25(10):1156-1166.
[3]Zhao X ,Okeke NL,Sharpe O,et al.
Circulating immune complexes contain citrullinated fibrinogen in rheumatoid arthritis[J].
Arthritis research&therapy,2008,10(4):1-13.
[4]Sokolove J,Zhao X,Chandra PE,et al.
Immune complexes containing citrullinated fibrinogen costimulate macrophages via Toll-like receptor 4 and Fcγreceptor[J].
Arthritis&Rheumatism,2011,63(1):53-62.
[5]Nydegger UE,Zubler RH,Gabay R,et al.
Circulating complement breakdown products in patients with rheumatoid arthritis.
Correlation between plasma C3d,circulating immune complexes,and clinical activity[J].
The Journal of clinical investigation,1977,59(5):862-868.
[6]Ramsey‐Goldman R ,Alexander RV,Massarotti EM,et al.
Complement activation in patients with probable systemic lupus erythematosus and ability to predict progression to American College of Rheumatology--classified systemic lupus erythematosus[J].
Arthritis&Rheumatology,2020,72(1):78-88 .
[7]Van der Pouw Kraan T,Wijbrandts CA,Van Baarsen LGM,et al.
Rheumatoid arthritis subtypes identified by genomic profiling of peripheral blood cells:assignment of a type I interferon signature in a subpopulation of patients[J].
Annals of the rheumatic diseases,2007,66(8):1008-1014.
[8]Higgs BW,Liu Z,White B,et al.
Patients with systemic lupus erythematosus,myositis,rheumatoid arthritis and scleroderma share activation of a common type I interferon pathway[J].
Annals of the rheumatic diseases,2011,70(11):2029-2036.
[9]Cantaert T,Van Baarsen LG,Wijbrandts CA,et al.
Type I interferons have no major influence on humoral autoimmunity in rheumatoid arthritis[J].
Rheumatology,2010,49(1):156-166.
[10]van Baarsen LGM,Wijbrandts CA,Rustenburg F ,et al.
Regulation of IFN response gene activity during infliximab treatment in rheumatoid arthritis is associated with clinical response to treatment[J].
Arthritis research&therapy,2010,12(1):1-10.
[11]Ishikawa Y,Fujii T, Ishikawa SK,et al.
Immunogenicity and lupus-like autoantibody production can be linked to each other along with type I interferon production in patients with rheumatoid arthritis treated with infliximab:a retrospective study of a single center cohort[J].
PloS one,2016,11(9):e0162896.
[12]De Rycke L,Baeten D,Kruithof E,et al.
The effect of TNFalpha blockade on the antinuclear antibody profile in patients with chronic arthritis:biological and clinical implications[J].
Lupus,2005,14(12):931-937.
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