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Diagnostic marker of rheumatoid arthritis and application thereof

A rheumatoid, arthritis technology, applied in the field of RA diagnostic markers

Active Publication Date: 2019-09-24
INST OF CHINESE MATERIA MEDICA CHINA ACAD OF CHINESE MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

30% of ACPA-positive / RF-positive patients with clinically suspected arthralgia did not develop RA within 2 years, therefore, suspected arthralgia and current clinical autoantibodies are not enough to accurately identify patients who will develop RA
[0007] As mentioned above, RA is a chronic autoimmune disease. Although the detection of autoantibody markers currently used in clinical practice plays an important role in the diagnosis of the disease, some RA patients are still negative for autoantibodies. Some patients with positive autoantibodies did not develop RA

Method used

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  • Diagnostic marker of rheumatoid arthritis and application thereof
  • Diagnostic marker of rheumatoid arthritis and application thereof
  • Diagnostic marker of rheumatoid arthritis and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Example 1 The role of RNase L in the pathogenesis and development of clinical RA patients

[0050] Obtain 20 clinical specimens of knee joint synovium from patients with RA and osteoarthritis (OA) after total knee arthroplasty in Wangjing Hospital of China Academy of Chinese Medical Sciences, Guang'anmen Hospital of Traditional Chinese Medicine, and China-Japan Friendship Hospital. There were no significant differences in baseline levels such as age. The synovial fluid was centrifuged at 3000rpm / min, and the supernatant was taken, and stored at -80°C; part of the synovial tissue was paraffin-embedded and sectioned, and part of it was cryopreserved to extract protein and RNA for subsequent detection.

[0051] 1. Significantly high expression of RNase L in the synovium of RA patients

[0052] We compared and analyzed the expression of RNase L in the joint synovium of patients with RA and OA. The results of immunohistochemical detection (performed according to the method ...

Embodiment 2

[0060] Example 2 Effect of RNase L on the pathogenesis of CIA mice

[0061] RNase L - / - Mice and WT mice (C57BL / 6J) were introduced from the laboratory of Prof. Aimin Zhou in the United States, and the genotype was identified by PCR method. C57BL / 6 WT mice and RNase L - / - The mice were randomly divided into two groups, namely WT-Control group, WT-Model group, RNase L - / - -Control group, RNase L - / - -Model group. In the model group, the collagen-induced arthritis (CIA) model was established. The model preparation method was to intradermally inject 0.1ml of chicken type II collagen and complete Freund's adjuvant emulsifier at the base of the tail of each mouse. 1. Secondary immunization with emulsifier on day 21; Control group was treated with equal volume of saline as control. From day 21, the joint swelling and joint index were observed, and knee joints were taken, routinely embedded in paraffin, sectioned, HE stained, and histopathologically scored.

[0062] 1. RNase L ...

Embodiment 3

[0069] Example 3 RNase L can promote the differentiation of macrophages to the M1 pro-inflammatory phenotype

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Abstract

The invention provides the use of an antibody reactive with RNase L or a fragment thereof for the preparation of a medicament for diagnosing a rheumatoid arthritis (RA) disease. The invention also provides the use of a ribonuclease L gene as a biomarker for the preparation of a medicament for diagnosing a rheumatoid arthritis disease. The RNase L is significantly highly expressed in the joint synovial membrane of a RA patient and is positively correlated with the secretion of TNF[alpha]. After RNase L gene knockout, a CIA mouse model incidence and arthritis score are significantly inhibited. The above results confirm that the RNase L promotes the occurrence and development of the RA. The RNase L is mainly expressed in macrophages, and promotes the differentiation of macrophages into proinflammatory M1 by activating a JAK / STAT1 pathway, thereby promoting a RA inflammatory response. In summary, the RNase L can be used as a biomarker of the rheumatoid arthritis diseases.

Description

technical field [0001] The invention belongs to the field of biological detection, and in particular relates to a RA diagnostic marker and its application. Background technique [0002] Rheumatoid arthritis (Rheumatoid arthritis, RA) is an autoimmune disease characterized by chronic synovitis and cartilage erosion, eventually leading to the destruction of bones and joints. Because the disease is continuous and recurrent, the disability rate is very high. High, it is a clinically refractory disease, which brings a heavy economic burden to the patient's family and society. According to the latest report, the two-year disability rate of untreated patients is about 50%, and the three-year disability rate is 70%. Due to the great differences in the incidence of RA, the sensitivity of RA diagnosis is not high at present, and a considerable part of early RA has bone and joint destruction before clinical diagnosis. , comprehensive diagnosis has been the continuous attention of the...

Claims

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Application Information

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IPC IPC(8): G01N33/564G01N33/573G01N33/532G01N33/533
CPCG01N33/564G01N33/573G01N33/532G01N33/533
Inventor 孔祥英林娜苏晓慧刘春芳刘翠玲苏红昌
Owner INST OF CHINESE MATERIA MEDICA CHINA ACAD OF CHINESE MEDICAL SCI
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