Frequency of FCGR3A Gene Polymorphisms in Patients with Neuromyelitis Optica Spectrum Disorders, Anti-oligodendrocyte Myelin Protein Antibody Disease, and Multiple Sclerosis. (PoGe)

March 5, 2025 updated by: Mirabella Massimiliano, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Multicenter Prospective Interventional Study to Evaluate the Frequency of FCGR3A Gene Polymorphisms in Patients with Neuromyelitis Optica Spectrum Disorders, Myelin Oligodendrocyte Glycoprotein Antibody Disease, and Multiple Sclerosis.

The goal of this study is to assess the frequency of genetic polymorphisms of the FCG3A in a cohort of Italian patients affected by neuromyelitis optica spectrum disorder (NMOSD) and mog antibody associated disease (MOGAD) and in a a comparison group of patients affected with Multiple Sclerosis (MS).

The study will involve adult patients diagnosed with MS, NMOSD, or MOGAD, followed at various clinical centers in the Lazio region.

Patients from the participating clinical centers will be selected, and their medical records will be analyzed to collect clinical and neuroimaging data. The data will include demographic information such as age, sex and body mass index and clinical information such as age at disease onset, disease duration, antibody status (AQP4+/- and MOG+/-), disease-modifying therapies, as well as MRI data and the Expanded Disability Status Scale (EDSS) score.

Each patient included in the study will undergo a single blood draw of approximately 5 ml of peripheral venous blood during routine blood tests, which will be used for DNA extraction and polimorphysm analysis. Demographic and clinical differences between patients with NMOSD and MOGAD, with and without the polymorphism, will be assessed and compared with the group of patients with MS.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

FCG receptors (FCGR) are proteins expressed by various immune cells that bind to the Fc portion of immunoglobulin G (IgG). They play a key role in innate and adaptive immunity, regulating inflammatory responses and preventing autoimmunity. Genetic studies have shown that variations in FCGR genes can influence these functions, altering phagocytosis capacity and inflammatory response.

One particularly relevant polymorphism is SNP rs396991 in the FCGR3A gene, which encodes the receptor expressed on NK cells, monocytes, and macrophages. This SNP causes the substitution of the amino acid phenylalanine (F) with valine (V) at position 158, modifying the receptor's affinity for IgG. The 158V variant is associated with an enhanced inflammatory response, while 158F is linked to reduced immune complex clearance, contributing to the pathogenesis of autoimmune diseases such as lupus, rheumatoid arthritis, and sarcoidosis.

Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are two inflammatory disorders of the central nervous system, often severe and recurrent. NMOSD is characterized by autoantibodies against aquaporin-4 (AQP4), while MOGAD is associated with autoantibodies against MOG glycoprotein. There are currently no data on the frequency of the rs396991 polymorphism in the Italian population affected by these diseases.

The primary objective of this study is to assess the frequency of the FCGR3A-V158F genetic polymorphism in a cohort of Italian patients affected by NMOSD and MOGAD. A comparison group composed of patients diagnosed with Multiple Sclerosis (MS) will also be included.

The study will involve adult patients diagnosed with MS, NMOSD, or MOGAD, receiving care at various clinical centers in the Lazio region. Patients from the participating clinical centers will be selected, and their medical records, both paper-based and digital, will be reviewed to collect clinical and neuroimaging data. These data will be organized in an Excel database and will include information such as age, sex, ethnic background, body mass index, smoking status, presence of other autoimmune diseases, and non-neurological comorbidities. Additional recorded information will include diagnosis (NMOSD, MS, or MOGAD), age at disease onset, disease duration, antibody status (AQP4+/- and MOG+/-), previous disease-modifying therapies and their duration, as well as MRI data and Expanded Disability Status Scale (EDSS) scores.

For genetic analysis, each patient included in the study will undergo a blood draw of approximately 5 ml of peripheral venous blood (collected in EDTA) during routine blood tests. The sample will be used for DNA extraction, following the patient's signed informed consent. Genetic investigations will be conducted at the Genomic Medicine Section of the Department of Life Sciences and Public Health at Università Cattolica del Sacro Cuore in Rome. DNA samples will be stored anonymously for up to 10 years from the start of the project, with access restricted to authorized personnel. Patients or their families may request the destruction of their DNA at any time.

A total of 50 patients will be recruited, with a 12-month enrollment period and a total study duration of 24 months. The secondary objective is to identify potential differences in the clinical characteristics of NMOSD and MOGAD patients who express the polymorphism compared to those who do not.

Genetic analyses will be conducted at the Section of Genomic Medicine, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore (Rome). The extracted DNA will be stored anonymously with an alphanumeric code for a maximum of 10 years from the start date of the project at the same institution. Only a limited number of authorized personnel will have access to the samples and data, subject to approval from the principal investigator (Prof. Massimiliano Mirabella). If requested by the patient or their family, the DNA can be destroyed at any time.

DNA extraction will be performed using the Wizard Genomic DNA Isolation Kit (Promega) and quantified via spectrophotometer (Thermo Fisher) and agarose gel electrophoresis. The detection of the rs396991 polymorphism in the FCGR3A gene in patients with NMOSD, MS, and MOGAD will be carried out using Sanger sequencing, employing primers described by Mahaweni et al. (14).

The presence of Copy Number Variable Regions (CNRs) in the FCGR3A gene will be assessed through MLPA (MRC Holland) and will be reserved only for patients who test negative for the rs396991 polymorphism using the Sanger method.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Roma, Italy, 00168
        • Recruiting
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
        • Contact:
        • Contact:
          • Alessandra Cicia, Neurologist
        • Contact:
          • Assunta Bianco, Neurologist
        • Contact:
          • Matteo Lucchini, Neurologist

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adult patients diagnosed with MS, NMOSD, or MOGAD receiving care at participating centers
  • Patients aged ≥ 18 years
  • Ability to understand and sign informed consent

Exclusion Criteria:

  • Individuals under 18 years of age
  • Inability to provide informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Patients diagnosied with neuromyelitis optica spectrum disorder and MOG antibodies associated diseas
Patients will undergo a peripheral venous blood draw of approximately 5 ml (collected in EDTA) during routine blood tests for DNA extraction and genetic analysis, limited to the reserach of FCG3A polymorphisms. The results obtained will be compared with a control-group composed by patients diagnosed with Multiple sclerosis.
Procedure: Blood draw for the laboratory assessment
Blood draw of approximately 5 ml of peripheral venous blood (collected in EDTA) will be collected for DNA extraction and genetic analysis limited to the research of FCG3A polymorphisms
Other: Patients diagnosied with Multiple Sclerosis
Patients will undergo a peripheral venous blood draw of approximately 5 ml (collected in EDTA) during routine blood tests for DNA extraction and genetic analysis, limited to the reserach of FCG3A polymorphisms. This is a comparison group.
Procedure: Blood draw for the laboratory assessment
Blood draw of approximately 5 ml of peripheral venous blood (collected in EDTA) will be collected for DNA extraction and genetic analysis limited to the research of FCG3A polymorphisms

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
FCGR3A gene polymorphism frequency in a cohort of Italian patients affected by NMOSD and MOGAD.
Time Frame: Baseline
To assess the frequency of the FCGR3A gene polymorphism in a cohort of Italian patients affected by NMOSD and MOGAD.
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical characteristics of NMOSD and MOGAD patients who express the polymorphism
Time Frame: From enrollment to 24 months
Disability assessed by Expanded disability status scale in NMOSD and MOGAD patients who express the polymorphism and in to those who do not.
From enrollment to 24 months
Clinical characteristics of NMOSD and MOGAD patients who express the polymorphism
Time Frame: From enrollment to 24 months
Number of disease relapses in patients with NMOSD and MOGAD expressing the polymorphisms and in patients without the polymorphism
From enrollment to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 20, 2025

Primary Completion (Estimated)

February 28, 2026

Study Completion (Estimated)

February 28, 2027

Study Registration Dates

First Submitted

February 21, 2025

First Submitted That Met QC Criteria

March 5, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 5, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 7168

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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