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.

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.