Inflammatory Biomarkers in Multiple Sclerosis and Neuromyelitis Optica

Inflammatory biomarkers have emerged as critical tools for understanding and managing both multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). In these conditions, peripheral blood cell counts and derived indices reflect the balance between innate and adaptive immunity. Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) integrate simple haematological parameters to signal disease activity, predict relapses and gauge therapeutic response. Specific autoantibodies, such as aquaporin-4 immunoglobulin G, define NMOSD subtypes, while evolving genetic and cytokine analyses elucidate individual susceptibility and severity in MS. Blood–brain barrier integrity, monitored via serum and cerebrospinal fluid markers, further complements these indices, offering insight into central nervous system entry of inflammatory cells. Together, these biomarkers support non-invasive monitoring, stratification of clinical phenotypes and timely intervention in both disorders.

Research from Nature Portfolio

Recent studies have detailed white blood cell profiles in seropositive NMOSD and myelin oligodendrocyte glycoprotein antibody-associated disease. Patients with aquaporin-4 antibodies exhibited elevated neutrophil and monocyte counts alongside higher NLR and MLR, distinguishing them from healthy controls and from multiple sclerosis cohorts. Conversely, myelin oligodendrocyte glycoprotein antibody-positive individuals shared increased total leukocyte, neutrophil and monocyte counts but displayed distinct clustering patterns when compared with MS, highlighting divergent innate immune signatures across demyelinating conditions.

Further analyses in newly diagnosed MS have shown raised total leukocytes, monocytes, basophils and neutrophils at the time of first attack, irrespective of smoking status or body mass index, while lymphocyte and eosinophil counts remained unchanged. These elevations did not correlate with lesion burden on magnetic resonance imaging, suggesting that peripheral myeloid activation may precede or occur independently of radiological changes, reinforcing the potential of simple haematological indices as early markers of inflammatory activity.

Inflammatory Biomarkers in Multiple Sclerosis and Neuromyelitis Optica publication trend

The graph below shows the total number of articles in inflammatory biomarkers in multiple sclerosis and neuromyelitis optica across all publications each year (not limited to Nature Index journals).

Technical terms

Neutrophil-to-Lymphocyte Ratio (NLR): The quotient of absolute neutrophil count divided by absolute lymphocyte count, used to gauge systemic inflammation.

Monocyte-to-Lymphocyte Ratio (MLR): The ratio of circulating monocytes to lymphocytes, reflecting myeloid-adaptive immune balance.

Platelet-to-Lymphocyte Ratio (PLR): The division of platelet count by lymphocyte count, indicating inflammatory and thrombocytic activity.

Systemic Immune-Inflammation Index (SII): A composite index calculated as platelet count multiplied by NLR, integrating three haematological parameters.

Expanded Disability Status Scale (EDSS): A scale from 0 to 10 measuring neurological impairment and functional disability in demyelinating diseases.

Aquaporin-4 Immunoglobulin G (AQP4-IgG): Autoantibody targeting the water channel aquaporin-4, diagnostic for a subtype of NMOSD.

References

1. Causal association between the peripheral immunity and the risk and disease severity of multiple sclerosis. Frontiers in Immunology (2024).
2. White blood cell count profiles in anti-aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder and anti-myelin oligodendrocyte glycoprotein antibody-associated disease. Scientific Reports (2023).
3. White blood cell count profiles in multiple sclerosis during attacks before the initiation of acute and chronic treatments. Scientific Reports (2021).
4. Predictive role of blood-based indicators in neuromyelitis optica spectrum disorders. Frontiers in Neuroscience (2023).
5. The role of systemic ımmune ınflammatory ındex in showing active lesion ın patients with multiple sclerosis. BMC Neurology (2023).
6. Blood Brain Barrier Permeability Could Be a Biomarker to Predict Severity of Neuromyelitis Optica Spectrum Disorders: A Retrospective Analysis. Frontiers in Neurology (2018).