Increased Disability Progression in rs10191329^AA Carriers with Multiple Sclerosis Is Preceded by Neurofilament Light...

Area of Science:

• Neuroimmunology
• Genetics of Neurological Disorders
• Biomarkers in Multiple Sclerosis

Background:

• Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system.
• Identifying genetic factors influencing MS progression is crucial for personalized treatment strategies.
• Neuroaxonal damage, indicated by serum neurofilament light chain (sNfL) levels, is a key marker of MS activity.

Purpose of the Study:

• To investigate the association between the rs10191329 genetic risk variant and neuroaxonal damage (sNfL levels) in people with MS (pwMS).
• To determine the impact of the rs10191329 variant on disability progression and the development of secondary progressive MS (SPMS) in pwMS.

Main Methods:

• A cohort of 740 pwMS was analyzed, with prospective and retrospective monitoring over up to 40 years.
• Clinical outcomes, including Expanded Disability Status Scale (EDSS) and SPMS development, were assessed.
• Serum neurofilament light chain (sNfL) levels were measured using single-molecule array technology.

Main Results:

• No significant difference in sNfL levels at diagnosis was observed among homozygous, heterozygous, and non-carriers of the rs10191329 variant.
• Homozygous carriers exhibited higher sNfL levels preceding disease progression, a steeper increase in disability, and a greater likelihood of developing SPMS.
• These findings suggest a role for rs10191329 in predicting future MS disease course.

Conclusions:

• The rs10191329 genetic variant is associated with accelerated disability progression and increased risk of SPMS in people with MS.
• Genetic variants like rs10191329 can serve as valuable biomarkers for predicting MS disease progression.
• These insights support the development of personalized medicine approaches for MS risk assessment and management.