Assessment of Serum FAM19A5 Level in Egyptian Patients With Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica spectrum disorders (NMOSD) are severe inflammatory autoimmune conditions of the central nervous system (CNS) . The discovery of NMOSD-specific aquaporin 4 (AQP4) antibody has established that NMOSD is indeed a distinct entity . Approximately 80% of patients with NMOSD test positive for aquaporin-4 (AQP4) immunoglobulin G (IgG) antibodies .AQP4-IgG associated NMOSD appears to target astrocytes, not myelin, leading to elevated markers of astrocyte injury during attacks . Untill now there is limited research about understanding the biomarkers of astrocyte injury and the following reactive gliosis. Family with sequence similarity 19-memberA5 (FAM19A5) protein is postulated to regulate nervous and immune cells of the brain as a brain-specific chemokine, but its precise functional role is not well understood . A recent study suggested that FAM19A5 is secreted by reactive astrocytes following CNS damage and triggers reactive gliosis . In another recent study, serum FAM19A5 was higher in patients with NMOSD-AQP4 than in other CNS demyelinating diseases and healthy controls . So, we need to study the level of this novel biomarker among our Egyptian NMOSD patients and whether it shall be a new biomarker for NMOSD .

Moreover just few studies conducted on cognitive dysfunctions in NMOSD patients and they demonstrate a significant decrease of cognitive abilities and the prevalence of CI in different samples varies between 30 and 70% .So further studies are needed to investigate the cognitive performance in NMOSD patients

Study Overview

• Status: Not yet recruiting
• Conditions: Assessment of Serum FAM19A5level in Egyptian Patients With NMOSD
• Intervention / Treatment: Diagnostic test: serum level of FAM19A5

Detailed Description

Sixty patients diagnosed as NMOSD based on the recently revised 2015 international consensus diagnostic criteria for NMOSD ,attending Neurology clinic, Asyut University hospitals, Asyut university and Kasr Al-Ainy multiple sclerosis/neuroimmunology clinic, Cairo University hospitals, Cairo University, Egypt, through one and half year from study onset. Sixty healthy volunteers, without any neurological or systemic medical diseases, age and sex matched , will be enrolled as healthy controls(HCs).

Aim of the work :

1. Determining the serum level of FAM19A5 in a cohort of Egyptian patients with NMOSD in comparison with healthy controls and its relationship with the different clinical phenotypes and parameters and disease severity of NMOSD patients.
2. Cognitive performance of NMOSD patients in comparison with healthy controls.

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

• Study Contact: Name: sarah khairy, master; Phone Number: 01023742942; Email: sarahkhairy89@yahoo.com
• Study Contact Backup: Name: mohammed Abd elhameed, doctorate; Phone Number: 01002629734; Email: Moh78_abdelhamed@aun.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Sixty patients diagnosed as NMOSD based on the recently revised 2015 international consensus diagnostic criteria for NMOSD ,attending Neurology clinic, Asyut University hospitals, Asyut university and Kasr Al-Ainy multiple sclerosis/neuroimmunology clinic, Cairo University hospitals, Cairo University, Egypt, through one and half year from study onset. Sixty healthy volunteers, without any neurological or systemic medical diseases, age and sex matched , will be enrolled as healthy controls(HCs).

Description

Inclusion Criteria:

• 1-Both NMOSD AQP-4 +ve and AQP-4 -ve. 2-Age <18 and >60 years. 3-Both males and females. 4-Both receiving or not receiving current immunosuppressants. 5-Any score of extended disability status scale (EDSS).

Exclusion Criteria:

• 1-Any neuropsychiatric disorder other than NMOSD such as multiple sclerosis ,CNS infectious diseases or malignancy.

  2-Systemic conditions influencing analysis of clinical and serological data , such as general infection, malignancy, and hematologic diseases.

  3-Illiterate patients. 4-History of drug or alcohol abuse

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
60 case; Sixty patients diagnosed as NMOSD based on the recently revised 2015 international consensus diagnostic criteria for NMOSD (9) ,attending Neurology clinic, Asyut University hospitals, Asyut university and Kasr Al-Ainy multiple sclerosis/neuroimmunology clinic, Cairo University hospitals, Cairo University, Egypt, through one and half year from study onset	Diagnostic test: serum level of FAM19A5; Detection of serum level of FAM19A5 of patients and controls by using ELISA technique.
60 control; Sixty healthy volunteers, without any neurological or systemic medical diseases, age and sex matched , will be enrolled as healthy controls(HCs).	Diagnostic test: serum level of FAM19A5; Detection of serum level of FAM19A5 of patients and controls by using ELISA technique.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determining the serum level of FAM19A5 in NMOSD bpatients in relation to healthy controls by using ELISA technique	Determining the serum level of FAM19A5 in NMOSD patients in relation to healthy controls by using ELISA technique	one and half year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Episodic verbal learning and memory of patients and controls will be evaluated by using California verbal learning test second edition	California verbal learning test second edition (CVL ll)of patients and controls The median of each scale will be assessed for patients and age and sex matched healthy controls on the other side and the impairment will be assessed by comparison	one and half year

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: Hamdy EL tellawy, doctorate, Assiut University; Study Director: Nein Shalaby, doctorate, Cairo University

Publications and helpful links

General Publications

• Meng H, Xu J, Pan C, Cheng J, Hu Y, Hong Y, Shen Y, Dai H. Cognitive dysfunction in adult patients with neuromyelitis optica: a systematic review and meta-analysis. J Neurol. 2017 Aug;264(8):1549-1558. doi: 10.1007/s00415-016-8345-3. Epub 2016 Dec 1.
• Lee HL, Seok HY, Ryu HW, Cho EB, Kim BC, Kim BJ, Min JH, Seok JM, Shin HY, Kang SY, Kwon OH, Lee SS, Oh J, Sohn EH, Huh SY, Cho JY, Seong JY, Kim BJ. Serum FAM19A5 in neuromyelitis optica spectrum disorders: Can it be a new biomarker representing clinical status? Mult Scler. 2020 Nov;26(13):1700-1707. doi: 10.1177/1352458519885489. Epub 2019 Nov 4.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2022
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: April 9, 2022
• First Submitted That Met QC Criteria: July 4, 2022
• First Posted (Actual): July 7, 2022

Study Record Updates

• Last Update Posted (Actual): July 7, 2022
• Last Update Submitted That Met QC Criteria: July 4, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Eye Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Myelitis, Transverse; Optic Neuritis; Neuromyelitis Optica
• Other Study ID Numbers: Serum FAM9A5 in NMOSD patients

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