Biomarkers for Optimizing Immunotherapies in Multiple Sclerosis and Autoimmune CNS Diseases

Multiple sclerosis (MS) is the most debilitating, immune-mediated, and neurodegenerative disease among young adults, although there are patients at both ends of the age spectrum, with pediatric or late-onset forms.

Due to the involvement of several immune factors in MS immunopathology, both within and outside the CNS, many biomarkers have been studied over time, in relation to the onset, progression of the disease, clinical and imaging features, and ultimately the response to various immunotherapies. Initially, immunogenetic markers, including histocompatibility system alleles especially HLA-DRB *15:01, and the presence of oligoclonal bands in the CSF through electrophoresis, demonstrated a clear association with all aspects of the disease. Progressively, cytokines, chemokines, neurofilament light chain, glial fibrillary acidic protein (GFAP), chintinase, K-Index, optical coherence tomograph (OCT), multi-omics, etc. were added. Additionally, the improvement in MRI scans, both conventional and non-conventional increased the accuracy of diagnosis and differential diagnosis.
Several autoimmune CNS autoantibodies, such as anti-aquaporin-4 , anti-MOG, anti-N-methyl-D aspartate receptor and anti-GAD antibodies have been used to distinguish different forms of autoimmune CNS diseases and tailor appropriate treatment strategies. Over time, numerous studies have used these biomarkers to differentiate between MS and other demyelinating diseases within the neuromyelitis optica spectrum disorders (NMOSD), as well as other autoimmune encephalitides of the CNS. They also have been used to differentiate rare syndromes like Susac syndrome, or overlapping syndromes, with systemic autoimmune diseases, like Systemic Lupus Erythymatosus (SLE).

This Research Topic aims to highlight the potential of biomarkers in optimizing immunotherapies for MS and other autoimmune CNS diseases. The objective is to elucidate how recently discovered biomarkers align with therapeutic needs, propelling the development of personalized treatment strategies. We seek to understand which biomarkers are instrumental in maximizing immunotherapeutic efficacy and which provide the greatest promise for future treatment paradigms. The exploration focuses on further advancing our understanding of immunosenescence, immunometabolism, and systemic interrelations such as the gut-brain axis.

To gather further insights focusing on MS and autoimmune CNS conditions, we welcome articles addressing, but not limited to, the following themes:

• The role of novel biomarkers in differentiating CNS autoimmune diseases.

• Advances in neuroimaging techniques in diagnosing and managing MS.

• Interplay between the gut-brain axis and CNS immunology.

• The use of artificial intelligence in biomarker discovery and treatment personalization.

• Contributions of immunosenescence and cellular senescence to disease progression.

Researchers and clinicians are encouraged to contribute their findings and perspectives on these critical areas.