Abstract
BackgroundSerum hematological indices such as the neutrophil-lymphocyte ratio (NLR) or monocyte-lymphocyte ratio (MLR) have been used as biomarkers of pathogenic inflammation and prognostication in multiple areas of medicine; recent evidence shows correlation with psychological parameters as well.Objectives/Aims: To characterize clinical, neuroimaging, and psycho-neuro-immunological associations with NLR and MLR in persons with multiple sclerosis (MS).MethodsWe identified a large cohort of clinically well-defined patients from our longitudinal database that included MS-related outcomes, disease-modifying therapy, patient-reported outcome (PRO) measures, and quantified cerebral MRI at 1.5 T. We queried hospital records for complete blood counts within 2 months of each clinic visit and excluded those obtained during clinical relapses. Four hundred eighty-three patients, with a mean of 3 longitudinal observations each, were identified who met these criteria. Initial analyses assessed the association between NLR and MLR as the outcomes, and psychological and demographic predictors in univariable and multivariable models controlling for age, gender and treatment. The second set of analyses assessed the association between clinical and MRI outcomes including whole brain atrophy and T2-hyperintense lesion volume, with NLR and MLR as predictors in univariable and multivariable models. All analyses used a mixed effects linear or logistic regression model with repeated measures.ResultsUnadjusted analyses demonstrated significant associations between higher (log-transformed) NLR (but not MLR) and PRO measures including increasing depression (p = 0.01), fatigue (p < 0.01), and decreased physical quality of life (p < 0.01). Higher NLR and MLR strongly predicted increased MS-related disability as assessed by the Expanded Disability Status Scale, independent of all demographic, clinical, treatment-related, and psychosocial variables (p < 0.001). Lastly, higher NLR and MLR significantly discriminated progressive from relapsing status (p ≤ 0.01 for both), and higher MLR correlated with increased whole-brain atrophy (p < 0.05) but not T2 hyperintense lesion volume (p > 0.05) even after controlling for all clinical and demographic covariates. Sensitivity analyses using a subset of untreated patients (N = 146) corroborated these results.ConclusionsElevated NLR and MLR may represent hematopoetic bias toward increased production and pro-inflammatory priming of the myeloid innate immune system (numerator) in conjunction with dysregulated adaptive immune processes (denominator), and consequently reflect a complementary and independent marker for severity of MS-related neurological disability and MRI outcomes.
Highlights
Multiple sclerosis (MS) is a progressive neurodegenerative condition of presumed autoimmune etiology typically characterized by recurrent episodes of inflammatory demyelination and accelerated tissue destruction of the central nervous system
In both univariable and multivariable comparisons controlling for age, gender, smoking history, and disease-modifying therapy (DMT), neutrophil-lymphocyte ratio (NLR) was significantly higher for subjects taking cyclophosphamide and fingolimod, and significantly lower for subjects taking interferons and natalizumab
Increased NLR was significantly associated with higher depression (CES-D) scores, higher fatigue scores (MFIS), and lower physical quality of life (SF-36), but not social support as assessed by the Modified Study Social Support Survey (MSSS), or Body mass index (BMI)
Summary
Multiple sclerosis (MS) is a progressive neurodegenerative condition of presumed autoimmune etiology typically characterized by recurrent episodes of inflammatory demyelination and accelerated tissue destruction of the central nervous system. NLR improves outcome prediction in stroke [7, 8], and is elevated compared to healthy controls in degenerative conditions like Alzheimer’s [9, 10] and Parkinson’s [11] disease. Serum hematological indices such as the neutrophil-lymphocyte ratio (NLR) or monocyte-lymphocyte ratio (MLR) have been used as biomarkers of pathogenic inflammation and prognostication in multiple areas of medicine; recent evidence shows correlation with psychological parameters as well. Objectives/Aims: To characterize clinical, neuroimaging, and psycho-neuro-immunological associations with NLR and MLR in persons with multiple sclerosis (MS)
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