Interleukin and Autoantibodies in Myasthenia Gravis.
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Myasthenia Gravis cases Collection of Peripheral Blood Peripheral blood mononuclear cells (PBMCs) will be isolated from freshly drawn heparinized blood by ficoll density gradient centrifugation according to the manufacturer's protocol. Real-Time Reverse Transcription -PCR (RT-PCR) 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. Autoantibodies detection: 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. |
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
|
| Healthy Control Collection of Peripheral Blood Peripheral blood mononuclear cells (PBMCs) will be isolated from freshly drawn heparinized blood by ficoll density gradient centrifugation according to the manufacturer's protocol. Real-Time Reverse Transcription -PCR (RT-PCR) 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. |
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
|
Outcome Measures
Primary Outcome Measures
- Expression levels of Interleukin 37 [a year]
change in the expression levels of Interleukin 37 gene in the Myasthenia Gravis patients relative to the healthy control.
Secondary Outcome Measures
- Autoantibodies detection [a year]
Correlation of the gene expression levels with muscle specific kinase (MuSK) and low-density lipoprotein receptor-related protein (LRP4) autoantibodies serum level.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Clinical Diagnosis of Myasthenia Gravis.
-
Willingness to sample collection.
Exclusion Criteria:
-
History of chronic psychiatric or neurological disorder other than Myasthenia Gravis that can produce weakness or fatigue.
-
Severe systemic illness affecting life-expectancy ( chronic liver or kidney diseases).
-
History of autoimmune diseases, connective tissue diseases, , or genetic diseases.
-
Patients on large dosage of immune-suppressive treatment or Intravenous immunoglobulin in the recent 3 months.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Assiut University
Investigators
- Principal Investigator: Radwa Medhat, Dem, Assiut University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- myasthenia1932022