Clinical trial NCT02948855: Regulation of LncRNA For Breg in Patients With Thymoma and Autoimmune Diseases
Official title: Study on Regulation of LncRNA to Regulatory B Cells(Bregs) Through Notch Pathway in Patients With Thymoma and Autoimmune Diseases
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Thymoma
Autoimmune Disease
Keywords: Long non-coding RNA（LncRNA）
Thymoma
Autoimmune disease
Notch2 Signaling pathway
Regulatory B cell（Breg）
Lead sponsor: Tianjin Medical University Cancer Institute and Hospital
Sponsor class: OTHER
First posted: 2016-10-31
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 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.

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.

Detailed description: 1. This study plans to research the correlation between Bregs and thymoma complicated with autoimmune diseases and the regulation the severity of the disease.
2. Clarify different expression levels of Notch2 signaling pathway in thymoma complicated with autoimmune diseases, and the effect on Regulatory B Cells(Bregs).
3. Find the effective regulation mode of Notch2 signaling pathway and the regulation of Bregs cell development and function in LncRNA.

Eligibility 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.

Primary outcomes:
measure: The relationship between LncRNA and Notch2 signaling pathway
timeFrame: 2016.10.01~2018.09.31-up to 24 months
Secondary outcomes:
measure: The regulated effect of Notch2 signaling pathway to the development of Bregs and the cell function
timeFrame: 2016.10.01~2018.09.31-up to 24 months
Other outcomes:
measure: The relevance of Bregs and thymoma with autoimmune diseases
timeFrame: 2016.10.01~2018.09.31-up to 24 months
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University Cancer Institute and Hospital
name: Donghao Wang, director
role: STUDY_DIRECTOR
References:
citation: Strobel 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.
citation: 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.
citation: Klinker MW, Lundy SK. Multiple mechanisms of immune suppression by B lymphocytes. Mol Med. 2012 Feb 10;18(1):123-37. doi: 10.2119/molmed.2011.00333.
citation: Bray SJ. Notch signalling: a simple pathway becomes complex. Nat Rev Mol Cell Biol. 2006 Sep;7(9):678-89. doi: 10.1038/nrm2009.
citation: 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.
citation: 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.