Regulation of LncRNA For Breg in Patients With Thymoma and Autoimmune Diseases
Study Details
Study Description
Brief Summary
Initially investigators will find LncRNA which to be able to affect Notch2 signaling pathway; then confirm the relationship between Notch2 and LncRNA, and analysis the regulation mode of LncRNA to Notch2 signaling pathway, and to observe the correlation between LncRNA and thymoma complicated with autoimmune diseases.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Detailed Description
-
This study plans to research the correlation between Bregs and thymoma complicated with autoimmune diseases and the regulation the severity of the disease.
-
Clarify different expression levels of Notch2 signaling pathway in thymoma complicated with autoimmune diseases, and the effect on Regulatory B Cells(Bregs).
-
Find the effective regulation mode of Notch2 signaling pathway and the regulation of Bregs cell development and function in LncRNA.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Tm group Simple thymoma group:The patients have suffered thymoma only and have no other complications. |
|
Tm+MG group Thymoma complicated with myasthenia gravis (MG) group: The patients have suffered thymoma and myasthenia gravis in the mean time. |
|
Tm+MG+AD group Thymoma complicated with myasthenia gravis and other autoimmune diseases (AD) group: The patients have suffered thymoma, myasthenia gravis and other autoimmune diseases in the mean time. |
Outcome Measures
Primary Outcome Measures
- The relationship between LncRNA and Notch2 signaling pathway [2016.10.01~2018.09.31-up to 24 months]
Using of Real-Time Polymerase Chain Reaction(RT-PCR) and Western-Blot to find special LncRNA that can affect the Notch2 signaling pathway LncRNA's and Notch2 signaling pathway's gene and protein expression level Then, using of SiRNA to inhibit the expression of LncRNA or plasmid transfection to raise the expression of LncRNA, and observation of changes of Notch2 signaling pathway.
Secondary Outcome Measures
- The regulated effect of Notch2 signaling pathway to the development of Bregs and the cell function [2016.10.01~2018.09.31-up to 24 months]
Peripheral blood was obtained from participants, and Regulatory B Cells(Bregs) were extracted and cultured. SiRNA-Notch2 to inhibit the expression of Notch2 signaling pathway and plasmid transfection of Notch2 to raise the expression of Notch2 signaling pathway, Then, observation of the quantity (*10^6/ml) and morphological changes of Bregs; the expression differences of Notch2 signaling pathway and content level (pg/ml) of Interleukin-10 (IL-10) in culture supernatant
Other Outcome Measures
- The relevance of Bregs and thymoma with autoimmune diseases [2016.10.01~2018.09.31-up to 24 months]
Natural disease course (number of days) Treatment options: hormone dosage (mg), cytotoxic drug dosage (mg), 28 day mortality (%), treatment success rate. Laboratory examination: white blood cell (*10^9/L), hemoglobin (g/L), urinary protein (mg/L), titers of autoimmune antibody. Vital signs: heart rate (bpm), body temperature.
Eligibility Criteria
Criteria
Inclusion Criteria:
- (1) The patients with the diagnosis of mediastinal tumors (thymoma, thymic hyperplasia);
(2) The patients with the diagnosis of autoimmune diseases;
(3) Age of 18 years or older which expected to stay in ICU for≥5 days.
(4) APACHE II score > 15;
(5) The patients or authorized clients agree to participate in the clinical trial and sign the informed consent.
Exclusion Criteria:
- (1) the patients with circulatory, respiratory failure and major organ dysfunction after being endangered and transferred to ICU;
(2) patients with severe liver and renal dysfunction;
(3) pregnant or lactating women;
(4) patients who have not signed the informed consent;
(5) any factors that may be expected to increase the risk of patients or other factors that may interfere with the outcome of clinical trials.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Tianjin Medical University Cancer Institute and Hospital | Tianjin | Tianjin | China | 300060 |
Sponsors and Collaborators
- Tianjin Medical University Cancer Institute and Hospital
Investigators
- Study Director: Donghao Wang, director, Tianjin Medical University Cancer Institute and Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
- Bray SJ. Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol. 2006 Sep;7(9):678-89. Review.
- Kessel A, Haj T, Peri R, Snir A, Melamed D, Sabo E, Toubi E. Human CD19(+)CD25(high) B regulatory cells suppress proliferation of CD4(+) T cells and enhance Foxp3 and CTLA-4 expression in T-regulatory cells. Autoimmun Rev. 2012 Jul;11(9):670-7. doi: 10.1016/j.autrev.2011.11.018. Epub 2011 Dec 2.
- Klinker MW, Lundy SK. Multiple mechanisms of immune suppression by B lymphocytes. Mol Med. 2012 Feb 10;18:123-37. doi: 10.2119/molmed.2011.00333. Review.
- Matsumoto M, Baba A, Yokota T, Nishikawa H, Ohkawa Y, Kayama H, Kallies A, Nutt SL, Sakaguchi S, Takeda K, Kurosaki T, Baba Y. Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation. Immunity. 2014 Dec 18;41(6):1040-51. doi: 10.1016/j.immuni.2014.10.016. Epub 2014 Nov 4.
- Mauri C, Menon M. The expanding family of regulatory B cells. Int Immunol. 2015 Oct;27(10):479-86. doi: 10.1093/intimm/dxv038. Epub 2015 Jun 12. Review.
- Ströbel P, Hartmann E, Rosenwald A, Kalla J, Ott G, Friedel G, Schalke B, Kasahara M, Tomaru U, Marx A. Corticomedullary differentiation and maturational arrest in thymomas. Histopathology. 2014 Mar;64(4):557-66. doi: 10.1111/his.12279. Epub 2013 Nov 18.
- bc2016031