Clinical trial NCT05301153: Interleukin and Autoantibodies in Myasthenia Gravis.
Official title: Expression Levels of Interleukin 37 and Its Correlation With Autoantibodies and Disease Severity in Myasthenia Gravis Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Myasthenia Gravis
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2022-03-29
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The estimated minimum required sample size is 84 cases (42 case in each group). sample size was calculated using G\*power software 3.1.9.7. As this study aims to detect the large difference between the the group of Myasthenia Gravis patients relative to the healthy controls, so the calculation based on determining the large effect size.

Main statistical test is two tailed t-test to detect difference between two groups .

Effect size = 0.8 Alpha = 0.05 Power = 0.95 Allocation ratio = 1

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Expression levels of Interleukin 37
timeFrame: a year
Secondary outcomes:
measure: Autoantibodies detection
timeFrame: a year
Other outcomes:
Locations:
Study officials:
affiliation: Assiut University
name: Radwa Medhat, Dem
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: Crotty S. Follicular helper CD4 T cells (TFH). Annu Rev Immunol. 2011;29:621-63. doi: 10.1146/annurev-immunol-031210-101400.
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.
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 Apr 1;204(7):1736-1745. doi: 10.4049/jimmunol.1901176. Epub 2020 Feb 28.