Lifestyle factors in multiple sclerosis disability progression and silent brain damage: A cross-sectional study.

OBJECTIVE: To determine the association between lifestyle risk factors with 1/ the Multiple Sclerosis Severity Score (MSSS) and 2/ ongoing subclinical brain damage in non-active MS patients on high-efficacy treatment. METHODS: Cross-sectional study in persons with Multiple Sclerosis (PwMS) investigating lifestyle factors including cognitive reserve (CR), physical activity (PA), smoking status, alcohol use, dietary habits, body mass index (BMI), blood pressure (BP) and cholesterol ratio. Data were collected through validated questionnaires, clinical and laboratory examination. Serum Neurofilament light chain (sNfL) levels were used as a proxy for ongoing brain damage in a subgroup of persons with non-active MS on high-efficacy treatment. Multiple regression analysis (MRA) models explored the relationship between lifestyle factors with the MSSS score and sNfL. RESULTS: 351 PwMS were included (43.04 ± 11.77 years, 69.8% female). Higher CR and PA were associated with a lower MSSS; overweight or obesity and higher systolic BP with a higher MSSS. The MRA model explained 22.2% of the variance for MSSS (R².255, adjusted R².222). Higher BMI and BP were related to lower sNfL. Twenty-3% (R².279, adjusted R².230) of the variance was explained in the MRA model for sNfL. CONCLUSION: Our study suggests an association between a 'brain healthy lifestyle' with disability progression in MS. A cognitive and physical active lifestyle alongside a normal body weight and blood pressure may help to prevent future disability in MS. Longitudinal and interventional research is necessary to gain insight in the causal pathway of these risk factors in preventing disability progression in MS.

Cells to the Rescue: Emerging Cell-Based Treatment Approaches for NMOSD and MOGAD.

Cell-based therapies are gaining momentum as promising treatments for rare neurological autoimmune diseases, including neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody-associated disease. The development of targeted cell therapies is hampered by the lack of adequate animal models that mirror the human disease. Most cell-based treatments, including HSCT, CAR-T cell, tolerogenic dendritic cell and mesenchymal stem cell treatment have entered early stage clinical trials or have been used as rescue treatment in treatment-refractory cases. The development of antigen-specific cell-based immunotherapies for autoimmune diseases is slowed down by the rarity of the diseases, the lack of surrogate outcomes and biomarkers that are able to predict long-term outcomes and/or therapy effectiveness as well as challenges in the manufacturing of cellular products. These challenges are likely to be overcome by future research.

HLA Class II Genotype Does Not Affect the Myelin Responsiveness of Multiple Sclerosis Patients.

BACKGROUND: When aiming to restore myelin tolerance using antigen-specific treatment approaches in MS, the wide variety of myelin-derived antigens towards which immune responses are targeted in multiple sclerosis (MS) patients needs to be taken into account. Uncertainty remains as to whether the myelin reactivity pattern of a specific MS patient can be predicted based upon the human leukocyte antigen (HLA) class II haplotype of the patient. METHODS: In this study, we analyzed the reactivity towards myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP) and proteolipid protein (PLP) peptides using direct interferon (IFN)-γ enzyme-linked immune absorbent spot (ELISPOT). Next, the HLA class II haplotype profile was determined by next-generation sequencing. In doing so, we aimed to evaluate the possible association between the precursor frequency of myelin-reactive T cells and the HLA haplotype. RESULTS: Reactivity towards any of the analyzed peptides could be demonstrated in 65.0% (13/20) of MS patients and in 60.0% (6/10) of healthy controls. At least one of the MS risk alleles HLA-DRB1*15:01, HLA-DQA1*01:02 and HLA-DQB1*06:02 was found in 70.0% (14/20) of patients and in 20.0% (2/10) of healthy controls. No difference in the presence of a myelin-specific response, nor in the frequency of myelin peptide-reactive precursor cells could be detected among carriers and non-carriers of these risk alleles. CONCLUSION: No association between HLA haplotype and myelin reactivity profile was present in our study population. This complicates the development of antigen-specific treatment approaches and implies the need for multi-epitope targeting in an HLA-unrestricted manner to fully address the wide variation in myelin responses and HLA profiles in a heterogeneous group of MS patients.

Stronger Correlations between Neurophysiological and Peripheral Disease Biomarkers Predict Better Prognosis in Two Severe Diseases.

: 'Mind-body' debates assume that better brain-body associations are healthy. This study examined whether degree of associations between a neurophysiological vagal nerve index and peripheral disease biomarkers predict prognosis in pancreatic cancer (PC) and multiple sclerosis (MS). Sample 1 included 272 patients with advanced PC. Sample 2 included 118 patients with MS. We measured the vagal nerve index heart rate variability (HRV) derived from electrocardiograms. We examined associations between HRV and patients' peripheral disease biomarkers: CA19-9 in PC and neurofilament light chain (NFL) in MS. Associations between HRV and each biomarker were examined separately in patients who survived or died (PC), and in those with and without relapse during 12 months (MS). In PC, HRV was significantly inversely related to the tumor marker CA19-9 in patients who later survived (r = -0.44, p < 0.05) but not in those who died (r = 0.10, NS). In MS, HRV was significantly and inversely related to NFL only in those who did not relapse (r = -0.25, p < 0.05), but not in those who relapsed (r = -0.05, NS). The degree of association between a neurophysiological vagal marker and peripheral disease biomarkers has prognostic value in two distinct diseases.