Screening of Serum Exosomal miRNA as a Biomarker for Ocular Muscle Myasthenia Gravis

Screening of Serum Exosomal miRNA as a Biomarker for Ocular Muscle Myasthenia

Ocular muscle myasthenia gravis (Ocular Myasthenia Gravis, OMG) has a high incidence and is difficult to diagnose. It is very necessary to find specific diagnostic indicators for OMG. By collecting peripheral blood of OMG, systemic myasthenia gravis and healthy people, extract miRNAs derived from exosomes in the serum and perform high-throughput sequencing, then use bioinformatics analysis methods to screen specifically expressed miRNAs as biomarkers for OMG diagnosis .

Study Overview

• Status: Enrolling by invitation
• Conditions: Myasthenia Gravis
• Intervention / Treatment: Device: Body fluid diagnosis

Detailed Description

Part I: (1) Collect peripheral blood samples from patients with early-onset OMG, early-onset GMG and healthy subjects of age and sex matched who have been diagnosed for the first time and have not undergone any drug treatment. There are 6 cases in each group. Extract the secretion miRNA in serum and conduct high-throughput sequencing. Analyze and compare the differential expression miRNAs between OMG, GMG and healthy control groups by edgeR. The standard of differential expression is set as | logFC |>1, p<0.05. Use miRTarBase, TargetScan, and miRDB to predict target genes for differentially expressed miRNAs. Conduct GO enrichment and KEGG signaling pathway analysis on target genes. The STRING tool is used to construct the target gene protein interaction network (PPI). According to the importance of the target gene calculated by the maximum population concentration ratio (MCC) method, the top ten genes (hub genes) are selected and analyzed.

(2) Randomly collect peripheral blood samples from patients with early-onset OMG, early-onset GMG, and age-matched healthy subjects, with 10 samples in each group. The differentially expressed miRNAs obtained during the sequencing phase were validated using real-time fluorescence quantification (RT-qPCR). Construct a receiver operating characteristic curve (ROC) curve to evaluate the diagnostic efficacy of the identified miRNA.

• Study Type: Observational
• Enrollment (Estimated): 160

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510632
      • First Affiliated Hospital of Jinan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

People within age 18-50 years old who is diagnosed with OMG,GMG or healthy people.

Description

Inclusion Criteria:

• Clinical manifestations: fluctuating myasthenia;

  • neostigmine test positive; ③ AChR-Ab, Musk-Ab, LRP4-Ab antibodies positive; ④repetitive nerve stimulation or single fiber EMG Positive (comply with the first one of the above diagnostic criteria and any one of the other three, and at the same time exclude ophthalmoplegia caused by other diseases, the diagnosis can be confirmed).

Exclusion Criteria:

①Combined with other autoimmune diseases or other inflammatory diseases; ②Patients with tumorous diseases;

• Received targeted biologics, intravenous gamma globulin, plasma exchange therapy within three months before treatment; ④Pregnancy Status or lactation

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ocular myasthenia gravis group; Ocular myasthenia gravis,age between 18-50 years old	Device: Body fluid diagnosis; miRNAs derived from exosomes in the serum
General myasthenia gravis group; General myasthenia gravis,age between 18-50 years old	Device: Body fluid diagnosis; miRNAs derived from exosomes in the serum
Healthy control group; people who are healthy without any systemic diseases，18-50 years old	Device: Body fluid diagnosis; miRNAs derived from exosomes in the serum

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A specific miRNA maybe miR-340-5p，miR-106b-5p or miR-27a-3p is a biological marker for diagnosis of OMG	find some specific miRNA to diagnose OMG.	12,2022

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Jinan University

Study record dates

Study Major Dates

• Study Start (Estimated): July 4, 2023
• Primary Completion (Estimated): March 31, 2024
• Study Completion (Estimated): May 31, 2024

Study Registration Dates

• First Submitted: November 4, 2021
• First Submitted That Met QC Criteria: May 25, 2023
• First Posted (Actual): June 5, 2023

Study Record Updates

• Last Update Posted (Actual): June 5, 2023
• Last Update Submitted That Met QC Criteria: May 25, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: miRNA; exosomes; Ocular myasthenia gravis
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis
• Other Study ID Numbers: 2021.11JinanU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No