Interleukin and Autoantibodies in Myasthenia Gravis.

Myasthenia Gravis Clinical Trial

Official title:

Expression Levels of Interleukin 37 and Its Correlation With Autoantibodies and Disease Severity in Myasthenia Gravis Patients

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05301153
• Other study ID #: myasthenia1932022
• Status: Not yet recruiting
• Start date: July 1, 2022
• Est. completion date: December 1, 2024

Study information

• Verified date: April 2022
• Source: Assiut University
• Contact: Noha Afifi, Prof
• Phone: 01006261108
• Email: nohaafifi2015[@]aun.edu.eg
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Myasthenia gravis is a B-cell-mediated autoimmune disorders causing muscle weakness due to defective synaptic transmission at the neuromuscular junction caused by autoantibodies to acetylcholine receptors in (∼85%), muscle specific kinase in 6% and low-density lipoprotein receptor-related protein 4.The detection of these autoantibodies is very important not only in the diagnosis, but also for the stratification of Myasthenia Gravis patients into respective subgroups. These groups can differ in clinical manifestations, prognosis and response to therapies which become relevant for the development of antigen-specific therapies, targeting only the specific autoantibodies involved in the autoimmune response.

Description:

Follicular T cells play a vital role during autoimmune disorders. The enhanced number or activation of these cells results in hyperproliferation of autoreactive B cells and overproduction of antibodies. Interleukin-37 is a newly identified immune-suppressive factor. It acts as an inhibitor of inflammation and plays an important regulatory role in both innate and adaptive immune responses. In Myasthenia Gravis, Cluster of differentiation 4+ T cell is the dominant cellular source for Interleukin-37 production directed to T follicular helper and B cells .It represses cell proliferation and secretion of autoantibody indicating that Interleukin-37 is a critical regulatory factor. The immunosuppressive features of Interleukin 37 contributing to autoimmune diseases are important and still poorly investigated. For this reason, the present study is designed to detect the level of expression of Interleukin 37 in Myasthenia Gravis patients and its correlation with autoantibodies serum levels and disease severity.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 82
• Est. completion date: December 1, 2024
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Clinical Diagnosis of Myasthenia Gravis.

2. Willingness to sample collection.

Exclusion Criteria:

1. History of chronic psychiatric or neurological disorder other than Myasthenia Gravis that can produce weakness or fatigue.

2. Severe systemic illness affecting life-expectancy ( chronic liver or kidney diseases).

3. History of autoimmune diseases, connective tissue diseases, , or genetic diseases.

4. Patients on large dosage of immune-suppressive treatment or Intravenous immunoglobulin in the recent 3 months.

Related Conditions & MeSH terms

• Muscle Weakness
• Myasthenia Gravis

Intervention

Diagnostic Test:
• real time PCR , ELISA
Real-time RT PCR will be performed on complementary DNA produced from 250 ng total RNA using the following primers Interleukin 37, F: 59-CAGTGAGGTCAGCGATTAGGAA-39 R: 59-TTAGTGAGCAGGTTTGGTGTTTT-39 b-actin, F: 59-CACCATTGGCAATGAGCGGTTC-39 R 59-AGGTCTTTGCGGATGTCCACGT-39. Detection of autoantibodies to muscle specific kinase (MuSK) and low-density lipoprotein receptor-related protein 4 (LRP4) serum levels by ELISA

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (5)

Crotty S. Follicular helper CD4 T cells (TFH). Annu Rev Immunol. 2011;29:621-63. doi: 10.1146/annurev-immunol-031210-101400. Review. — View Citation

Fichtner ML, Jiang R, Bourke A, Nowak RJ, O'Connor KC. Autoimmune Pathology in Myasthenia Gravis Disease Subtypes Is Governed by Divergent Mechanisms of Immunopathology. Front Immunol. 2020 May 27;11:776. doi: 10.3389/fimmu.2020.00776. eCollection 2020. R — View Citation

King C, Tangye SG, Mackay CR. T follicular helper (TFH) cells in normal and dysregulated immune responses. Annu Rev Immunol. 2008;26:741-66. doi: 10.1146/annurev.immunol.26.021607.090344. Review. — View Citation

Lazaridis K, Tzartos SJ. Autoantibody Specificities in Myasthenia Gravis; Implications for Improved Diagnostics and Therapeutics. Front Immunol. 2020 Feb 14;11:212. doi: 10.3389/fimmu.2020.00212. eCollection 2020. Review. — View Citation

Liu Z, Zhu L, Lu Z, Chen H, Fan L, Xue Q, Shi J, Li M, Li H, Gong J, Shi J, Wang T, Jiang ML, Cao R, Meng H, Wang C, Xu Y, Zhang CJ. IL-37 Represses the Autoimmunity in Myasthenia Gravis via Directly Targeting Follicular Th and B Cells. J Immunol. 2020 Ap — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Expression levels of Interleukin 37	change in the expression levels of Interleukin 37 gene in the Myasthenia Gravis patients relative to the healthy control.	a year
Secondary	Autoantibodies detection	Correlation of the gene expression levels with muscle specific kinase (MuSK) and low-density lipoprotein receptor-related protein (LRP4) autoantibodies serum level.	a year