Evaluation of Two Cell-based Assays for Diagnosing MOG-IgG Associated Disorders

Evaluation of The Diagnostic Value of Two Cell-based Assays for MOG-IgG-associated Diseases: A Multicenter, Paired Design Observational Study

Anti-myelin oligodendrocyte glycoprotein-IgG-associated disorders (MOGAD) is a rare inflammatory autoimmune disease. In addition, since the international MOGAD group proposed live-cell based assays for MOGAD diagnosis in 2023, there are still no real-world cohort validation studies on this methodology. This study intends to establish a large sample cohort with multi-center and paired design. MOG-IgG detection based on live cells and fixed cells was performed on the study participants with high suspicion of MOGAD and the negative control population, to obtain the diagnostic performance parameters and consistency evaluation of the two methodologies, evaluate their clinical diagnostic value, and explore the best individual assay cutoffs for MOG-IgG detection suitable for the diagnosis of MOGAD in China.

Study Overview

• Status: Recruiting
• Conditions: Myelin Oligodendrocyte Glycoprotein (MOG)-Antibody Related Disorders
• Intervention / Treatment: Diagnostic test: CBA method of live cells and fixed cells

Detailed Description

Study design: A multicenter, observational study to compare the diagnosis performance of two cell-based assays in Chinese patients with idiopathic demyelinating disorders Participants: In this study, serum samples were collected from participants with high clinical suspicion of MOGAD (the number of valid positive cases was 150), and control samples were collected (including 30 participants in other inflammatory CNS disease studies, 30 participants in non-inflammatory CNS studies, and 30 participants in healthy people studies).

Aim: In this multicenter study, a cell-based assay (CBA) based on cell transfection was proposed to semi-quantitatively detect specific antibodies in human serum samples of study participants with highly suspected clinical manifestations of MOGAD and the control population. Each study participant used two CBA detection methods to detect MOG-IgG at the same time, namely live cell based and fixed cell based, to obtain diagnostic performance parameters and consistency evaluation (sensitivity, specificity, positive predictive value, negative predictive value) of the two methods, and combined with comprehensive clinical diagnosis to compare their clinical diagnostic value. To explore the individual assay cutoffs for the diagnosis of MOGAD in China.

Total enrollment: participants with high clinical suspicion of MOGAD (the number of valid positive cases was 150), and control samples were collected (including 30 participants in other inflammatory CNS disease studies, 30 participants in non-inflammatory CNS studies, and 30 participants in healthy people studies).

Time frame: August 1, 2024 to December 1, 2025.

Study protocol:

1. This study intends to include participants with a high likelihood of MOGAD, and to simultaneously match a negative control group including inflammatory CNS disease, non-inflammatory CNS disease, and healthy people. Serum samples of the above study participants were detected by CBA method of live cells and fixed cells. According to the comprehensive diagnosis results of clinical experts, the specificity, sensitivity, positive predictive value and negative predictive value of the two methods were compared, and the clinical consistency of the two methods was obtained.
2. According to the comprehensive clinical diagnosis results, the consistency of MOG-IgG positive and titer results between active CBA method and fixed CBA method was evaluated.
3. According to the comprehensive clinical diagnosis, the diagnostic value of MOGAD in different titers of the two methods was evaluated. To obtain the best individual assay cutoffs of MOGAD diagnosis in this study and improve the specificity of disease diagnosis.
4. The proportion of study participants with high suspicion of MOGAD who were diagnosed with MOGAD was counted, and the clinical characteristics of participants in this part of the study were analyzed to explore the correlation between MOG-IgG antibody titers and clinical characteristics, treatment regimen, clinical course, or disease activity.

Official Title Evaluation of the diagnostic value of two cell-based assays for MOG-IGG-associated diseases: a multicenter, paired design observational study Conditions MOG-IgG detection Intervention / Treatment Diagnostic Test: CBA method of live cells and fixed cells.

• Study Type: Observational
• Enrollment (Estimated): 240

Contacts and Locations

• Study Contact: Name: Chao Quan; Phone Number: 86 13651957283; Email: chao_quan@fudan.edu.cn
• Study Contact Backup: Name: Jingzi Zhangbao; Phone Number: 86 13661682637; Email: zhangbaojingzi@163.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200040
      • Recruiting
      • Huashan Hospital
      • Contact: Ying Mao; Phone Number: 86 52888828; Email: maoying@fudan.edu.cn

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Individual medical units plan to collect serum samples from clinically suspected MOGAD study participants (150 valid positive cases will be the cutoff for sample collection) between September 2024 and December 2024.

Description

Inclusion Criteria:

• age ≥18 years old, male and female.
• MOGAD is highly suspected.
• Other inflammatory CNS disease control groups include: According to the diagnostic criteria and consensus of various diseases, the diagnosis of multiple sclerosis, Autoimmune encephalitis (except NMDAR encephalitis), Guillain-Barre syndrome (GBS), Chronic Inflammatory Demyelinating polyradiculopathy (CIDP), Retinal Cerebrovascular disease (SUSAC), POEMS syndrome (POEMS), and neuropathy were confirmed. The monoclonal gammopathy of unknown significance (MGUS), Sarcoidosis and so on.
• The control group of non-inflammatory central nervous system diseases included: Migraine, CSVD, benign cranial hypertension, Glioma with definite diagnosis and no other autoimmune diseases.
• Healthy controls include healthy people who have no autoimmune diseases through physical examination and other means.
• Complete clinical data.
• Informed consent of the patient or his guardian has been obtained.

Exclusion Criteria:

• According to the Guidelines for Diagnosis and Treatment of Optic Neuromyelitis Spectrum Diseases (2021), patients with optic Neuromyelitis Spectrum diseases (NMOSD) with positive AQP4 were clearly diagnosed.
• According to the Expert Consensus on the Diagnosis and Treatment of Autoimmune encephalitis in China (2022), the diagnosis was confirmed as NMDAR encephalitis.
• Patients with positive anti-glial fibrillary acidic protein antibody (GFAP-IgG) in serum and/or cerebrospinal fluid.
• Lack of clinical data.
• Unqualified blood samples.
• The patient's informed consent was not obtained.
• Misdiagnosis in the research process went wrong in this study.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study participants with high clinical suspicion of MOGAD; Based on the "Chinese Expert Consensus on the Diagnosis and Treatment of Myelin Oligodendrocyte Glycoprotein Immunoglobulin MOG-IgG Antibody Associated Diseases" and the "Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria" in2023	Diagnostic test: CBA method of live cells and fixed cells; Study participants with high clinical suspicion of MOGAD: 2mL serum samples were collected for detection. CBA method of live cells and fixed cells was used for all samples. Sensitivity, specificity, positive predictive value and negative predictive value of the two detection methods were calculated according to the detection results and combined with the 2023 MOGAD diagnostic criteria.; Control group：2mL serum samples were collected for detection. CBA method of live cells and fixed cells was used for all samples.
Control group; including 30 participants in the study of other inflammatory CNS diseases, 30 participants in the study of non-inflammatory CNS and 30 participants in the study of healthy people	Diagnostic test: CBA method of live cells and fixed cells; Study participants with high clinical suspicion of MOGAD: 2mL serum samples were collected for detection. CBA method of live cells and fixed cells was used for all samples. Sensitivity, specificity, positive predictive value and negative predictive value of the two detection methods were calculated according to the detection results and combined with the 2023 MOGAD diagnostic criteria.; Control group：2mL serum samples were collected for detection. CBA method of live cells and fixed cells was used for all samples.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
diagnostic performance parameters and consistency evaluation	Each study participant used two cell-based assays to detect MOG-IgG simultaneously, namely live cell based and fixed cell based, to obtain the diagnostic performance parameters and consistency evaluation (sensitivity, specificity, positive predictive value, negative predictive value) of the two methodologies.	August 1, 2024 to December 1, 2025.

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Investigators: Principal Investigator: Quan Chao, Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2024
• Primary Completion (Actual): June 30, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: September 25, 2024
• First Submitted That Met QC Criteria: September 26, 2024
• First Posted (Actual): October 1, 2024

Study Record Updates

• Last Update Posted (Estimated): October 1, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: KY2024-1005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No