Biomarkers In Multiple Sclerosis Research Articles

Mitochondrial DNA Copy Number as a Biomarker of Multiple Sclerosis

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS). In its early stages, it results in inflammation, demyelination, and axonal loss. Egypt has the highest rates in the Middle East region. The pathogenicity of MS involves mitochondrial function. Damage to mitochondrial DNA (mtDNA) can produce variation in the copy number (CN) and decline in mitochondrial function. Our goal was to determine the potential of mtDNA-CN as a biomarker of MS and the progression of the disease. The study included 25 patients with relapsing remitting MS (RRMS) and 25 age and sex matched apparently healthy control. Two peripheral blood samples were collected from each patient, one during the remission phase and the other during the phase of relapse. A quantitative real-time polymerase chain reaction (qPCR) was performed to assess CN of mitochondrial DNA. There was a statistically significant decline in the number of mtDNA copies during the remission phase as compared to controls (p<0.01), yet no difference was seen between mtDNA-CN in relapsing subjects versus controls. Moreover, the copy number of mtDNA during the relapse phase was significantly higher than the remission phase suggesting the ability of mtDNA to differentiate between remission and relapse phases (p<0.05). Our study observed that mtDNA-CN at a cut off (0.75), can differentiate between RRMS patients in the remission phase and controls with a sensitivity of 56%, specificity 84%, positive predictive value (PPV) 65.6% and negative predictive value (NPV) 77.8%, and at a cut off (1), mtDNA-CN can differentiate between remission and relapse MS patients with a sensitivity 72%, specificity 56%, PPV 62.1% and NPV 66.7%. In conclusion, mtDNA-CN can be proposed as a biomarker of MS.

Paramagnetic rim lesions lead to pronounced diffuse periplaque white matter damage in multiple sclerosis

Background: Paramagnetic rim lesions (PRLs) are an imaging biomarker in multiple sclerosis (MS), associated with a more severe disease. Objectives: To determine quantitative magnetic resonance imaging (MRI) metrics of PRLs, lesions with diffuse susceptibility-weighted imaging (SWI)-hypointense signal (DSHLs) and SWI-isointense lesions (SILs), their surrounding periplaque area (PPA) and the normal-appearing white matter (NAWM). Methods: In a cross-sectional study, quantitative MRI metrics were measured in people with multiple sclerosis (pwMS) using the multi-dynamic multi-echo (MDME) sequence post-processing software “SyMRI.” Results: In 30 pwMS, 59 PRLs, 74 DSHLs, and 107 SILs were identified. Beside longer T1 relaxation times of PRLs compared to DSHLs and SILs (2030.5 (1519–2540) vs 1615.8 (1403.3–1953.5) vs 1199.5 (1089.6–1334.6), both p < 0.001), longer T1 relaxation times were observed in the PRL PPA compared to the SIL PPA and the NAWM but not the DSHL PPA. Patients with secondary progressive multiple sclerosis (SPMS) had longer T1 relaxation times in PRLs compared to patients with late relapsing multiple sclerosis (lRMS) (2394.5 (2030.5–3040) vs 1869.3 (1491.4–2451.3), p = 0.015) and also in the PRL PPA compared to patients with early relapsing multiple sclerosis (eRMS) (982 (927–1093.5) vs 904.3 (793.3–958.5), p = 0.013). Conclusion: PRLs are more destructive than SILs, leading to diffuse periplaque white matter (WM) damage. The quantitative MRI-based evaluation of the PRL PPA could be a marker for silent progression in pwMS.

Biomarkers in multiple sclerosis: An update

Over the past decade, a considerable number of biomarkers have been evaluated in neurological disorders. In this review we provide a summary of various clinical, biological, genetic, and imaging biomarkers of multiple sclerosis with a focus on their clinical significance and utility.

Improving the efficiency of free kappa light chains as diagnostic biomarker of Multiple Sclerosis by using a novel algorithm

BackgroundIntrathecal immunoglobulin synthesis (ITS) plays a crucial role in the diagnosis of multiple sclerosis (MS). Traditionally, the gold standard method for detecting ITS has been through the analysis of oligoclonal bands (OCB). However, the paradigm has shifted with the introduction of the free kappa light chains (FKLC) method. In fact, a recent consensus recommends evaluating FKLC index (FKLCi) as the primary approach and reserving oligoclonal bands with borderline results. The objective of our study is to investigate the diagnostic efficiency of combining FKLC with other methods to predict ITS while minimizing the reliance on OCB. MethodsA total of 192 patients were included in the study, consisting of 145 individuals diagnosed with multiple sclerosis (pwMS) and 46 with other neurological diseases (controls). Among the MS cases, 100 patients were assigned to the Training Cohort (TC), while an external Validation Cohort (VC) comprised of 45 MS patients was established. Diagnostic efficiency was assessed for FKLCi, OCB, Link index, and the Reiber formula for IgG and FKLC. Optimal cutoff values for Link index and FKLCi were also determined. The last procedure was developed for diverse algorithms using the parameters mentioned above, which included the optimal cutoffs previously obtained. The calculations were conducted independently for both the TC and the VC, as well as for a composite cohort formed by combining data from all patients (OC) ResultsOne algorithm, named KRO, was developed based on the determination of FKLCi and Reiber Formula as the primary diagnostic parameters. For cases where the FKLCi result was mildly increased, OCB was utilized as a supplementary test. The KRO algorithm demonstrated superior diagnostic accuracy in the OC (89%), resulting in a reduction of OCB consumption by 91%. DiscussionThe KRO algorithm demonstrated superior sensitivity and accuracy although lower specificity and NPV compared to the use of FKLCi and OCB alone. The present research aligns with the new consensus recommendations regarding the diagnostic approach. Our findings indicate that employing a combined marker approach via KRO could prove to be a proficient screening tool for multiple sclerosis. This approach also holds the potential to address inherent limitations associated with each individual marker. However, to further validate and solidify the efficacy of our algorithm, additional studies involving larger cohorts are warranted.

MicroRNAs as biomarkers of multiple sclerosis progression

Multiple sclerosis (MS) is an autoimmune inflammatory neurodegenerative disease of the central nervous system. The disease is characterized by a heterogeneous clinical course, which is reflected in the fact that there are various types, such as relapsing-remitting MS (RRMS), primary and secondary progressive MS (PPMS and SPMS, respectively). Currently, there is an active search for MS biomarkers capable of predicting and assessing disease progression with high sensitivity and specificity, which would be of great benefit in determining treatment tactics and evaluating their efficacy. MicroRNAs (miRNAs) are short (21–25 nucleotides) non-coding RNA molecules that are primarily involved in post-transcriptional regulation of gene expression. miRNAs play an essential role in tissue development, homeostasis, immune system regulation, and immune cell maturation; they are also involved in the pathophysiology of MS. In addition, high hopes are pinned on miRNAs as disease biomarkers, mainly due to their stability and ability to be released from cells into the extracellular space and circulate there for a long time. The review considers published data on miRNAs in different types of MS. In the future, changes in their levels may be used to create a panel of prognostic markers for disease progression. Studies of miRNAs levels in both circulating fluids (plasma, serum, cerebrospinal fluid) and brain tissue of MS patients were reviewed. Based on the aggregated data from the studies reviewed, it can be confirmed that the accumulated data are quite sufficient to recognize that regulatory miRNAs molecules are involved in the pathophysiological mechanisms of MS progression. However, there is still a long way to go to establish a panel of circulating miRNAs that predict the rate of progression of MS.

Is the ganglion cell layer thickness to macular thickness ratio a new biomarker for multiple sclerosis?

Ganglion cell layer thickness (GCLT)-to-total macular thickness (MT) is a new parameter that has not been studied in multiple sclerosis (MS) before. The current study aims to reveal the status of the GCLT-to-MT ratio in MS and its role in supporting the diagnosis of MS. In this retrospective and cross sectional study, the medical records of the MS patients between January 2016 and December 2021 were reviewed. Age-sex matched healthy control group was generated. Demographic and clinical data recorded. All participants were examined using a spectral-domain optic coherence tomography (OCT) device. Retinal layers, choroidal thickness (CT) was recorded. GCLT-to-MT ratio was calculated. A total of 74 eyes of 37 MS (9 male,28 female) patients and 82 eyes of 41 control (13 male, 28 female) were included in the study. The mean age was 37 ± 9.0 (years) in MS group. The MS patients and the control group were compared in terms of OCT parameters, CT was thicker at all regions in MS patients (p < 0.001). Macular thickness, GCLT, and inner plexiform layer thickness (IPLT) were thinner than the control group (p < 0.05). For distinguishing MS patients from healthy subjects, AUROC values for central GCLT/MT, temporal GCLT/MT, superior GCLT/MT, nasal GCLT/MT, and inferior GCLT/MT were 0.717, 0.689, 0.694, 0.733, and 0.740, respectively. In conclusion MT, GCLT, and IPLT thickness were thinner in MS patients, regardless of optic neuritis. The AUROC values of GCLT/MT were high and GCLT/MT ratio may be a helpful modality in demonstrating retinal neurodegeneration in MS patients.

Choroid Plexus Volume Change-A Candidate for a New Radiological Marker of MS Progression.

(1) Background: Multiple sclerosis (MS) is an auto-immune, chronic, neuroinflammatory, demyelinating disease that affects mainly young patients. This progressive inflammatory process causes the chronic loss of brain tissue and results in a deterioration in quality of life. To monitor neuroinflammatory process activity and predict the further development of disease, it is necessary to find a suitable biomarker that could easily be used. In this research, we verify the usability of choroid plexus (CP) volume, a new MS biomarker, in the monitoring of the progression of multiple sclerosis disease. (2) Methods: A single-center, prospective study with three groups of patients was conducted based on the following groups: MS patients who received experimental cellular therapy (Treg), treatment-naïve MS patients and healthy controls. (3) Results: This study concludes that there is a correlation between the CPV/TIV (choroid plexus/total intracranial volume) ratio and the progress of multiple sclerosis disease-patients with MS (MS + Treg) had larger volumes of choroid plexuses. CPV/TIV ratios in MS groups were constantly and significantly growing. In the Treg group, patients with relapses had larger plexuses in comparison to the group with no relapses of MS. A similar correlation was observed for the GD+ group (patients with postcontrast enhancing plaques) compared against the non-GD group (patients without postcontrast enhancing plaques). (4) Conclusion: Choroid plexus volume, due to its immunological function, correlates with the inflammatory process in the central nervous system. We consider it to become a valuable radiological biomarker of MS activity.

Short-term brain atrophy evolution after initiation of immunotherapy in a real-world multiple sclerosis cohort.

In multiple sclerosis (MS), brain atrophy measurements have emerged as an important biomarker reflecting neurodegeneration and disability progression. However, due to several potential confounders, investigation of brain atrophy in clinical routine and even in controlled clinical studies can be challenging. The aim of this study was to investigate the short-term dynamics of brain atrophy development after initiation of disease-modifying therapy (DMT) in a "real-world setting." In this retrospective study, we included MS patients starting DMT (natalizumab, fingolimod, dimethyl fumarate, or interferon-ß1a) or without DMT, availability of a baseline MRI, and two annual follow-up scans on the same MRI system. Two-timepoint percentage brain volume changes (PBVCs) were calculated. Fifty-five MS patients (12 patients starting DMT with natalizumab, 7 fingolimod, 14 dimethyl fumarate, 11 interferon-ß1a, and 11 patients without DMT) were included. We found the highest PBVCs in the first 12 months after initiation of natalizumab treatment. Furthermore, the PBVCs in our study were very much comparable to the results observed by other groups, as well as for fingolimod, dimethyl fumarate, and interferon-ß1a. We found PBVCs that are comparable to the results of previous studies, suggesting that brain atrophy, assessed on 3D MRI data sets acquired on the same 3T MRI, provides a robust MS biomarker.

Biomarkers in Multiple Sclerosis: Analysis of the Present Advantages and Look to the Future

Biomarkers in Multiple Sclerosis: Analysis of the Present Advantages and Look to the Future

OCT and OCT-A biomarkers in multiple sclerosis - review.

Objective: Retinal neuronal and vascular changes have been observed in multiple sclerosis (MS) patients. The aim of this review was to highlight the most current optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) data in MS and to provide information about the possibility of using OCT / OCT-A parameters as biomarkers for screening, diagnosis and monitoring of MS. Methods: To carry out this review, a meticulous literature search was undergone on PubMed between 2014 and the present day, using the following terms: "multiple", "sclerosis", "optical", "coherence", "tomography" and "angiography". Additional studies were found via references, being chosen according to relevance. Results: Retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) were significantly lower in MS patients compared to controls, and correlated with clinical and paraclinical variables, such as visual function, disability, and magnetic resonance imaging (MRI). Retinal capillary plexuses could be higher, lower or the same, and the best OCT-A microvasculature parameter for the detection of MS was the superficial capillary plexus (SCP). The reduced retinal vessel density (VD) was correlated with the disability in MS. Conclusions: OCT and OCT-A parameters could improve the development of retinal biomarkers for screening, early diagnosis and monitoring the disease progression of MS, and they could improve the development of potential future therapies that could slow or stop the course of this incurable disease. Abbreviations: DCP = deep capillary plexus; EDSS = Expanded Disability Status Scale; GCC = ganglion cell complex; GCL = ganglion cell layer; MRI = magnetic resonance imaging; MS = Multiple sclerosis; OCT = optical coherence tomography; OCT-A = optical coherence tomography angiography; ON = optic neuritis; RNFL = retinal nerve fiber layer; SCP = superficial capillary plexus; VD = vessel density.

Leukocyte telomere length in women with multiple sclerosis: Comparison with healthy women during pregnancy and puerperium

ObjectivesSeveral studies indicated leukocyte telomere length (LTL) as a biomarker of multiple sclerosis (MS) evolution. This study aimed to investigate LTL in women with multiple sclerosis (MS) compared to that in healthy women (HW) across different reproductive phases, and to evaluate its relationship with MS activity. MethodsBlood samples were collected from women with MS and HW during the fertile phase, pregnancy, and puerperium. LTL was determined using quantitative fluorescence in situ hybridization (Q-FISH). ResultsBlood samples from 68 women with MS (22 during fertile life, 23 during pregnancy, and 23 post-partum) and 52 HW (23 during fertile life, 20 during pregnancy, and 9 post-partum) were analyzed. During pregnancy, LTL in MS women and HW was 84.7 ± 10.5 and 77.6 ± 11.5, respectively (p < 0.005). Regression analysis showed that shorter LTL was associated with pregnancy in HW (p = 0.021); this relationship was not observed in MS women, for whom shorter LTL was related to a higher EDSS (p = 0.036). A longitudinal analysis was performed in eight MS women, showing LTL shortening from pregnancy to puerperium (p = 0.003), which was related to MS reactivation (p = 0.042). ConclusionOur results highlight the possible associations between LTL, reproductive biological phases, and MS activity after delivery.

Clinical associations and characteristics of the polyspecific intrathecal immune response in elderly patients with non-multiple sclerosis chronic autoimmune-inflammatory neurological diseases - a retrospective cross-sectional study.

The polyspecific intrathecal immune response (PSIIR), aka MRZ reaction (M = measles, R = rubella, Z = zoster, optionally Herpes simplex virus, HSV) is defined as intrathecal immunoglobulin synthesis (IIS) for two or more unrelated viruses. Although an established cerebrospinal fluid (CSF) biomarker for multiple sclerosis (MS), a chronic autoimmune-inflammatory neurological disease (CAIND) of the central nervous system (CNS) usually starting in young adulthood, the full spectrum of CAINDs with a positive PSIIR remains ill defined. In this retrospective, cross-sectional study, patients with CSF-positive oligoclonal bands (OCB) and - to enrich for non-MS diagnoses - aged ≥50 years were enrolled. Of 415 with PSIIR testing results (MRZ, HSV optional), 76 were PSIIR-positive. Of these, 25 (33%) did not meet the diagnostic criteria for MS spectrum diseases (MS-S) comprising clinically or radiologically isolated syndrome (CIS/RIS) or MS. PSIIR-positive non-MS-S phenotypes were heterogenous with CNS, peripheral nerve and motor neuron involvement and often defied unequivocal diagnostic classification. A rating by neuroimmunology experts suggested non-MS CAINDs in 16/25 (64%). Long-term follow-up available in 13 always showed a chronically progressive course. Four of five responded to immunotherapy. Compared to MS-S patients, non-MS CAIND patients showed less frequent CNS regions with demyelination (25% vs. 75%) and quantitative IgG IIS (31% vs. 81%). MRZ-specific IIS did not differ between both groups, while additional HSV-specific IIS was characteristic for non-MS CAIND patients. In conclusion, PSIIR positivity occurs frequently in non-MS-S patients ≥50 years. Although sometimes apparently coincidental, the PSIIR seems to represent a suitable biomarker for previously unnoticed chronic neurologic autoimmunities, which require further characterization.

Intrathecal kappa free light chain synthesis is associated with worse prognosis in relapsing–remitting multiple sclerosis

BackgroundWhile kappa free light chain (KFLC) index has become a useful diagnostic biomarker in multiple sclerosis (MS), its prognostic properties are less explored. B cells play a crucial role in MS pathogenesis, but the impact from increased intrathecal production of immunoglobulins and KFLC remains to be determined. Recently, it has become evident that insidious worsening is not confined to progressive MS but is also common in relapsing–remitting MS (RRMS), a feature known as progression independent of relapse activity (PIRA).MethodsWe retrospectively identified 131 patients with clinically isolated syndrome or early RRMS who had determined KFLC index as part of their diagnostic workup. Demographic and clinical data were extracted from the Swedish MS registry. Associations of baseline KFLC index with evidence of disease activity (EDA) and PIRA were investigated in multivariable cox proportional hazards regression models.ResultsKFLC index was significantly higher in PIRA (median 148.5, interquartile range [IQR] 106.9–253.5) compared with non-PIRA (78.26, IQR 28.93–186.5, p = 0.009). In a multivariable cox regression model adjusted for confounders, KFLC index emerged as an independent risk factor for PIRA (adjusted hazard ratio [aHR] 1.005, 95% confidence interval [CI] 1.002–1.008, p = 0.002). Dichotomized by the cut-off value KFLC index > 100, patients with KFLC index > 100 had an almost fourfold increase in the risk for developing PIRA. KFLC index was also predictive of evidence of disease activity during follow-up.ConclusionsOur data indicate that high KFLC index at baseline is predictive of PIRA, EDA-3, and overall worse prognosis in MS.

Relevance of kappa free light chains index in patients with aquaporin-4 or myelin-oligodendrocyte-glycoprotein antibodies.

The kappa free light chains index (κ-index) is increasing in importance as a fast, easy, cost-effective, and quantitative biomarker in multiple sclerosis (MS), which can replace cerebrospinal fluid (CSF)-restricted oligoclonal bands (OCB) detection. In previous studies, controls often included mixed patients with several inflammatory central nervous system disorders. The aim of the present study was to assess the κ-index in patients with serum aquaporin-4 (AQP4)-IgG or myelin-oligodendrocyte-glycoprotein (MOG)-IgG. We analyzed CSF/serum samples of patients with AQP4-IgG or MOG-Ig and evaluated distinct κ-index cut-offs. We described clinical and magnetic resonance imaging (MRI) features of patients with the highest κ-index values. In 11 patients with AQP4-IgG, median κ-index was 16.8 (range 0.2; 63) and 6/11 (54.5%) had κ-index >12. Among 42 patients with MOG-IgG, 2 had low positive MOG-IgG titers, were ultimately diagnosed with MS, and had a markedly increased κ-index (54.1 and 102.5 respectively). For the remaining 40 MOG-IgG-positive patients the median κ-index was 0.3 (range 0.1; 15.5). Some 6/40 (15%) and 1/40 (2.5%) patients had a κ-index >6 and >12, respectively. None fulfilled MRI dissemination in space and dissemination in time (DIS/DIT) criteria and the final diagnosis was MOG-IgG-associated disease (MOGAD) for these 40 patients. Four of the 40 (10%) MOG-IgG-positive patients had OCB. While a marked increase in κ-index could discriminate MS from MOGAD, a low κ-index threshold could lead to confusion between MS and MOGAD or AQP4 antibody-positive neuromyelitis optica spectrum disorder.

Dilated Virchow-Robin spaces are a marker for arterial disease in multiple sclerosis.

Virchow-Robin spaces (VRS) have been associated with neurodegeneration and neuroinflammation. However, it remains uncertain to what degree non-dilated or dilated VRS reflect specific features of neuroinflammatory pathology. Thus, we aimed at investigating the clinical relevance of VRS as imaging biomarker in multiple sclerosis (MS) and to correlate VRS to their histopathologic signature. In a cohort study comprising 142 MS patients and 30 control subjects, we assessed the association of non-dilated and dilated VRS to clinical and magnetic resonance imaging (MRI) outcomes. Findings were corroborated in a validation cohort comprising 63 MS patients. Brain blocks from 6 MS patients and 3 non-MS controls were histopathologically processed to correlate VRS to their tissue substrate. In our actively treated clinical cohort, the count of dilated centrum semiovale VRS was associated with increased T1 and T2 lesion volumes. There was no systematic spatial colocalization of dilated VRS with MS lesions. At tissue level, VRS mostly corresponded to arteries and were not associated with MS pathological hallmarks. Interestingly, in our exvivo cohort comprising mostly progressive MS patients, dilated VRS in MS were associated with signs of small vessel disease. Contrary to prior beliefs, these observations suggest that VRS in MS do not associate with an accumulation of immune cells. But instead, these findings indicate vascular pathology as a driver and/or consequence of neuroinflammatory pathology for this imaging feature. NIH, Swedish Society for Medical Research, Swiss National Science Foundation and University of Zurich.

ID: 217582 Assessment of Spinal Cord and Sensory Evoked Potentials as Neurophysiological Biomarkers of Multiple Sclerosis

Demyelination is a hallmark of Multiple Sclerosis (MS), and yet, few existing measures of MS currently used in the clinic are specific measures of myelination. As remyelinating therapeutics enter the clinic, indices of myelination may serve as early prognostic read outs of therapeutic efficacy. Multimodal evoked potentials (EP), neurophysiological measures of signal transduction across the central nervous system, offer several advantages over current approaches. For one, EPs offer the ability to stimulate and record from various sensory and motor modalities, allowing for assessment of deficits across multiple functional systems at once. Moreover, EPs may be more sensitive to subclinical demyelination, which may promote earlier detection and treatment of MS.

Emerging imaging and liquid biomarkers in multiple sclerosis.

The advent of highly effective disease modifying therapy has transformed the landscape of multiple sclerosis (MS) care over the last two decades. However, there remains a critical, unmet need for sensitive and specific biomarkers to aid in diagnosis, prognosis, treatment monitoring, and the development of new interventions, particularly for people with progressive disease. This review evaluates the current data for several emerging imaging and liquid biomarkers in people with MS. MRI findings such as the central vein sign and paramagnetic rim lesions may improve MS diagnostic accuracy and evaluation of therapy efficacy in progressive disease. Serum and cerebrospinal fluid levels of several neuroglial proteins, such as neurofilament light chain and glial fibrillary acidic protein, show potential to be sensitive biomarkers of pathologic processes such as neuro-axonal injury or glial-inflammation. Additional promising biomarkers, including optical coherence tomography, cytokines and chemokines, microRNAs, and extracellular vesicles/exosomes, are also reviewed, among others. Beyond their potential integration into MS clinical care and interventional trials, several of these biomarkers may be informative of MS pathogenesis and help elucidate novel targets for treatment strategies.

Iron Rim Lesions as a Specific and Prognostic Biomarker of Multiple Sclerosis: 3T-Based Susceptibility-Weighted Imaging.

This study aimed to identify the clinical significance of iron rim lesions (IRLs) in distinguishing multiple sclerosis (MS) from other central nervous system (CNS) demyelinating diseases, determine the relationship between IRLs and disease severity, and understand the long-term dynamic changes in IRLs in MS. We retrospectively evaluated 76 patients with CNS demyelinating diseases. CNS demyelinating diseases were classified into three groups: MS (n = 30), neuromyelitis optica spectrum disorder (n = 23), and other CNS demyelinating diseases (n = 23). MRI images were obtained using conventional 3T MRI including susceptibility-weighted imaging. Sixteen of 76 patients (21.1%) had IRLs. Of the 16 patients with IRLs, 14 were in the MS group (87.5%), indicating that IRLs were significantly specific for MS. In the MS group, patients with IRLs had a significantly higher number of total WMLs, experienced more frequent recurrence, and were treated more with second-line immunosuppressive agents than were patients without IRLs. In addition to IRLs, T1-blackhole lesions were observed more frequently in the MS group than in the other groups. IRLs are specific for MS and could represent a reliable imaging biomarker to improve the diagnosis of MS. Additionally, the presence of IRLs seems to reflect more severe disease progression in MS.

Sex-dependent expression levels of VAV1 and P2X7 in PBMC of multiple sclerosis patients.

Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system and the leading cause of progressive neurological disability in young adults. It decreases the patient's lifespan by about 10 years and affects women more than men. No medication entirely restricts or reverses neurological degradation. However, early diagnosis and treatment increase the possibility of a better outcome. To identify new MS biomarkers, we tested the expression of six potential markers (P2X4, P2X7, CXCR4, RGS1, RGS16 and VAV1) using qPCR in peripheral blood mononuclear cells (PBMC) of MS patients treated with interferon β (IFNβ), with glatiramer acetate (GA) or untreated. We showed that P2X7 and VAV1 are significantly induced in MS patients. In contrast, the expression of P2X4, CXCR4, RGS1 and RGS16 was not significantly modified by MS in PBMC. P2X7 and VAV1 are essentially induced in female patients, suggesting these markers are connected to sex-specific mechanisms. Strikingly, VAV1 expression is higher in healthy women than healthy men and IFNβ treatment of MS reduced VAV1 expression in female MS patients while it up-regulated VAV1 in male MS patients. Our data point to the differential, sex-dependent value of MS markers and treatment effects. Although rgs16 expression in PBMC was not a valid MS marker in patients, the strong upregulation of P2X4 and P2X7 induced in the spinal cord of WT mice by EAE was abrogated in rgs16KO mice suggesting that rgs16 is required for P2X4 and P2X7 induction by neurological diseases.

N°268 – Navigated transcranial magnetic stimulation: A new tool to find biomarkers in multiple sclerosis

N°268 – Navigated transcranial magnetic stimulation: A new tool to find biomarkers in multiple sclerosis