Biomarkers in Autoimmune Disease of Nervous System

Biomarkers of Neurological Autoimmune Diseases

Neurological autoimmune diseases are a group of disorders characterized by the abnormal immune response attacking the nervous system, including the brain, spinal cord and peripheral nerves. These diseases exhibit high heterogeneity, diverse clinical presentations, and are challenging to diagnose and manage due to a lack of effective treatments. In this study, the investigators will recruit eight kinds of autoimmune diseases of nervous system including Neuromyelitis Optica Spectrum Disorder (NMOSD), Myasthenia Gravis (MG), Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), idiopathic inflammatory myopathy (IIM), and multiple sclerosis (MS), autoimmune encephalitis (AE), Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD). Through this study, the investigators aim to discover biomarkers with high sensitivity, specificity, and stability, which can support early diagnosis, disease monitoring, and personalized treatment for neurological autoimmune diseases, thereby improving the quality of life and prognosis for patients.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Myasthenia Gravis; Neuromyelitis Optica Spectrum Disorder; Autoimmune Encephalitis; Guillain-Barre Syndrome; Idiopathic Inflammatory Myopathies; Chronic Inflammatory Demyelinating Polyradiculoneuropathy; Stiff-Person Syndrome; Acute Disseminated Encephalomyelitis
• Intervention / Treatment: Diagnostic test: biomaker levels

Detailed Description

Autoimmune diseases of the nervous system are a type of disease in which the human immune system mistakenly attacks its own nervous system, causing damage to the structure and function of the nervous system. Its main pathogenic mechanism is that autoimmune cells, autoantibodies and other immune molecules directly or indirectly attack the nervous system. Autoimmune diseases of the nervous system can affect the central nervous system, peripheral nervous system and neuromuscular junction, leading to pathological changes such as neuronal or axonal damage, demyelination, and destruction of neuromuscular junction. Autoimmune diseases of the nervous system are relatively rare, with a wide range of damage and complex and diverse clinical manifestations. They have the characteristics of complexity of immune diseases and high mortality and disability of nervous system diseases. At present, the understanding of the disease is limited, and some diseases are difficult to diagnose. Globally, it is a major cause of disability in young and middle-aged people and can cause huge social and economic burdens. However, due to the lack of a series of relatively reliable prognostic predictors, it is impossible to carry out personalized immunotherapy to achieve the best therapeutic effect, and serious adverse events may occur. Proteomics, metabolomics, intestinal microorganisms and intestinal high-throughput targeted metabolomics, exosomes, miRNA sequencing, single-cell transcriptome sequencing and other detection methods and lymphocyte subsets have been hot topics in the study of various diseases in recent years. It has been found that abnormalities in the expression and function of certain genes, proteins, metabolites, miRNAs, intestinal flora and lymphocyte subsets are closely related to the occurrence and development of many diseases and the functional disability of patients, and have a good suggestive effect on prognosis judgment.

• Study Type: Observational
• Enrollment (Estimated): 50000

Contacts and Locations

• Study Contact: Name: Luo-qi Zhou, MD; Phone Number: 86-27-83663337; Email: zhouluoqi@tjh.tjmu.edu.cn

Study Locations

• China
  • Wuhan, China, 430030
    • Recruiting
    • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
    • Contact: Dai-shi Tian, Dr; Phone Number: 86-27-83663337; Email: tiands@tjh.tjmu.edu.cn

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with neurological autoimmune disease admission to Department of Neurology and Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from June 1, 2024 - May 31, 2034.

Description

Inclusion Criteria:

• Clinical diagnosis with autoinflammatory diseases of the nervous system, including: Neuromyelitis Optica Spectrum Disorder (NMOSD), Myasthenia Gravis (MG), Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP), idiopathic inflammatory myopathy(IIM), multiple sclerosis (MS), autoimmune encephalitis (AE), Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD), ect al.
• sex and age-matched healthy individuals

Exclusion Criteria:

• Known history of primary immunodeficiency (innate or acquired).
• Patients with severe central nervous system, pulmonary, or other systemic infections.
• Patients with secondary central nervous system demyelinating lesions, such as those caused by vasculitis, systemic lupus erythematosus, and Sjögren's syndrome.
• Patients with vascular (including hemorrhagic and ischemic), hereditary metabolic, neoplastic, or toxic diseases.
• Pregnant or lactating women.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
autoimmune disease; clinical diagnosis with autoimmune disease of central nervous system	Diagnostic test: biomaker levels; this study will discover and validate novel biomarkers (including blood, feces, bone marrow and lymph nodes etc al) of various neurological autoimmune diseases
health control; age- and sex-matched control individuals	Diagnostic test: biomaker levels; this study will discover and validate novel biomarkers (including blood, feces, bone marrow and lymph nodes etc al) of various neurological autoimmune diseases

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	Death during the follow-up in every single reason	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Autoimmune disease of any kind	Brain or spinal MRI scans will be used to detect the presence of any autoimmune disease, including multiple sclerosis, neuromyelitis optica spectrum disorder, acute disseminated encephalomyelitis, autoimmune encephalitis, Guillain-Barré syndrome, and myasthenia gravis.	10 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accumulated total active MRI lesions	the number of accumulate total active MRI lesions after CT103A infusion	10 years
Expanded Disability Status Scale (EDSS) score	EDSS and its associated functional system (FS) score provide a system for quantifying disability and monitoring changes in the level of disability over time. EDSS is a scale for assessing neurologic impairment in multiple sclerosis (MS). It consists of 7 FS (visual FS, brainstem FS, pyramidal FS, cerebellar FS, sensory FS, bowel and bladder FS, and cerebral FS) which are used to derive EDSS score ranging from 0 (normal neurological exam) to 10 (death from MS). A negative change from baseline indicates improvement. A participant was considered to have a worsening in overall EDSS score of at least 2 if baseline EDSS score was 0, or at least 1 point if baseline EDSS score is 1 to 5, or at least 0.5 point if baseline EDSS score is 5.5 or more.	10 years
Visual acuity	Corrected visual acuity is determine by Snellen E chart held at a distance of 5 meters. Higher score indicates better vision.	10 years
Quantitative Myasthenia Gravis Score (QMG)	Quantitative Myasthenia Gravis Score (QMG) range from 0 to 3. The normal person scored 0 and the higher score represent sever clinical symptom.	10 years
Myasthenia Gravis Activities if Daily Living (MG-ADL) Score	The MG-ADL is an eight-question survey of symptom severity, with each response graded from 0 (normal) to 3 (most severe). Two questions concern ocular, three oropharyngeal, one respiratory, and two extremity functions. Cumulative MG-ADL scores range from 0 to 24	10 years
Inflammatory Neuropathy Cause and Treatment (INCAT) Score	The INCAT score comprises two parts, the arm score and the leg score. Based on a patient's level of impairment in their arms and legs, each part is scored between 0 and 5 points, resulting in an INCAT total score between 0 and 10.	10 years
Medical Research Council (MRC) muscle function Score	The MRC score system for testing and grading of muscle function aims to provide a standardized and objective way to assess muscle function. It ranges from 0 to 5.	10 years
Manual Muscle Testing (MMT) Score	For MMT score, 16 muscle groups/ motions will be tested (not individual muscles). 14 of these are tested bilaterally. The score range from 0 to 10. A score of 10 is normal and a score of 0 is the worst.	10 years
36-item Short Form Generic Health Survey (SF-36) score	SF-36 will used to understand the health related quality-of -life of the subjects after CT103A infusion. The eight health concepts: limitations in physical activities because of health problems; limitations in social activities because of physical or emotional problems; limitations in usual role activities because of physical health problems; bodily pain; general mental health (psychological distress and well-being); limitations in usual role activities because of emotional problems; vitality (energy and fatigue); and general health perceptions will be searched. These outcomes will be grouped as physical component summary and mental component summary. The norm data is 0-100, the health related quality of life is increases as the scores are increased. The average score is 50.	10 years
EuroQol-five dimensions (EQ-SD) score	Health status is measured with the EuroQuality of Life Five Dimensions (EQ-5D) after CT103A infusion, which includes five dimensions and is used to evaluate the quality of life of sepsis survivors. They are mobility, self-care, usual activities, discomfort or pain and depression or anxiety. Levels are coded 1-5 and a total score is then generated. Results for the demographic measured will be displayed as a percentage value.	10 years
Visual analogue scale (VAS) pain score	usual visual analog scale (VAS) of pain is used to evaluate pain after CT103A infusion (line from 0: no pain to 10:worst pain)	10 years
Changes of concentration( pg/mL) of cytokines	such as ferritin, CRP, IL-6 and procalcitonin) will be analyzed	10 years
Profiling of immune cell subtypes	Changes in immune cells (including proportion of CD3+ T cells, CD3+CD4+ T cells and CD3+CD8+ T cells, ratio of CD4+ T/CD8+T) in blood, CSF and other immune organs will be analyzed through flow cytometry and single cell sequencing.	10 years
Modified Rankin Scale	Modified Rankin Scale (mRS) is a profoundly valid and reliable measure of disability and is broadly utilized for assessing stroke outcomes and degree of disability. A favorable outcome was characterized as mRS ranging from zero up to two, while unfavorable outcome ranging for 3 up to 6.	10 years

Collaborators and Investigators

• Sponsor: Tongji Hospital
• Investigators: Principal Investigator: Dai-shi Tian, MD, Tongji Hospital

Publications and helpful links

General Publications

• McPherson RC, Anderton SM. Adaptive immune responses in CNS autoimmune disease: mechanisms and therapeutic opportunities. J Neuroimmune Pharmacol. 2013 Sep;8(4):774-90. doi: 10.1007/s11481-013-9453-9. Epub 2013 Apr 9.
• Stenager E. A global perspective on the burden of multiple sclerosis. Lancet Neurol. 2019 Mar;18(3):227-228. doi: 10.1016/S1474-4422(18)30498-8. Epub 2019 Jan 21. No abstract available.
• Solomon AJ, Arrambide G, Brownlee WJ, Flanagan EP, Amato MP, Amezcua L, Banwell BL, Barkhof F, Corboy JR, Correale J, Fujihara K, Graves J, Harnegie MP, Hemmer B, Lechner-Scott J, Marrie RA, Newsome SD, Rocca MA, Royal W 3rd, Waubant EL, Yamout B, Cohen JA. Differential diagnosis of suspected multiple sclerosis: an updated consensus approach. Lancet Neurol. 2023 Aug;22(8):750-768. doi: 10.1016/S1474-4422(23)00148-5.

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: June 18, 2024
• First Submitted That Met QC Criteria: July 13, 2024
• First Posted (Actual): July 15, 2024

Study Record Updates

• Last Update Posted (Estimated): November 20, 2024
• Last Update Submitted That Met QC Criteria: November 17, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Biomarker; Immune cell; Autoimmune Diseases of the Nervous System
• Additional Relevant MeSH Terms: Neuroinflammatory Diseases; Post-Infectious Disorders; Musculoskeletal Diseases; Brain Diseases; Central Nervous System Diseases; Muscular Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Immune System Diseases; Infections; Peripheral Nervous System Diseases; Disease; Eye Diseases; Demyelinating Autoimmune Diseases, CNS; Demyelinating Diseases; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Spinal Cord Diseases; Leukoencephalopathies; Central Nervous System Infections; Polyneuropathies; Syndrome; Multiple Sclerosis; Myasthenia Gravis; Neuromyelitis Optica; Autoimmune Diseases; Nervous System Diseases; Encephalitis; Myositis; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Polyradiculoneuropathy; Autoimmune Diseases of the Nervous System; Stiff-Person Syndrome; Encephalomyelitis; Guillain-Barre Syndrome; Encephalomyelitis, Acute Disseminated
• Other Study ID Numbers: TJ-IRB202406068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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