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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Myasthenia Gravis cases |
Detection of autoantibodies to muscle specific kinase (MuSK) and low-density lipoprotein receptor-related protein 4 (LRP4) serum levels by ELISA according to the manufacturer's protocol. |
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| Healthy Control |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| real time PCR , ELISA | Diagnostic Test | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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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
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Noha Afifi, Prof | Contact | 01006261108 | nohaafifi2015@aun.edu.eg | |
| Fatma Sayed, lecturer | Contact | 01007424480 | fatmasayed@aun.edu.eg |
| Name | Affiliation | Role |
|---|---|---|
| Radwa Medhat, Dem | Assiut University | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32547535 | Result | 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. | |
| 32117321 | Result | 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. |
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| ID | Term |
|---|---|
| D009157 | Myasthenia Gravis |
| ID | Term |
|---|---|
| D020361 | Paraneoplastic Syndromes, Nervous System |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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|
| 21314428 | Result | Crotty S. Follicular helper CD4 T cells (TFH). Annu Rev Immunol. 2011;29:621-63. doi: 10.1146/annurev-immunol-031210-101400. |
| 18173374 | Result | 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. |
| 32111731 | Result | 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. |
| D010257 | Paraneoplastic Syndromes |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D019636 | Neurodegenerative Diseases |
| D020511 | Neuromuscular Junction Diseases |
| D009468 | Neuromuscular Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |