The Impact of Multiple Sclerosis Disease Status and Subtype on Hematological Profile.
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ABSTRACT:
SUBMITTER: Miller JM
PROVIDER: S-EPMC8004915 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). There is currently no single definitive test for MS. Circulating exosomes represent promising candidate biomarkers for a host of human diseases. Exosomes contain RNA, DNA, and proteins, can cross the blood-brain barrier, and are secreted from almost all cell types including cells of the CNS. We hypothesized that serum exosomal miRNAs could present a useful blood-based assay for MS disease detection and monitoring. Exosome-associated microRNAs in serum samples from MS patients (n?=?25) and matched healthy controls (n?=?11) were profiled using small RNA next generation sequencing. We identified differentially expressed exosomal miRNAs in both relapsing-remitting MS (RRMS) (miR-15b-5p, miR-451a, miR-30b-5p, miR-342-3p) and progressive MS patient sera (miR-127-3p, miR-370-3p, miR-409-3p, miR-432-5p) in relation to controls. Critically, we identified a group of nine miRNAs (miR-15b-5p, miR-23a-3p, miR-223-3p, miR-374a-5p, miR-30b-5p, miR-433-3p, miR-485-3p, miR-342-3p, miR-432-5p) that distinguished relapsing-remitting from progressive disease. Eight out of nine miRNAs were validated in an independent group (n?=?11) of progressive MS cases. This is the first demonstration that microRNAs associated with circulating exosomes are informative biomarkers not only for the diagnosis of MS, but in predicting disease subtype with a high degree of accuracy.
| S-EPMC5662562 | biostudies-literature
Project description:Using recently available mass sequencing and assembly technologies, we have been able to identify and quantify unique cell-free DNA motifs in the blood of patients with multiple sclerosis (MS). The most common MS clinical syndrome, relapsing-remitting MS (RRMS), is accompanied by a unique fingerprint of both inter- and intragenic cell-free circulating nucleic acids as specific DNA sequences that provide significant clinical sensitivity and specificity. Coding genes that are differentially represented in MS serum encode cytoskeletal proteins, brain-expressed regulators of growth, and receptors involved in nervous system signal transduction. Although coding genes distinguish RRMS and its clinical activity, several repeat sequences, such as the L1M family of LINE elements, are consistently different in all MS patients and clinical status versus the normal database. These data demonstrate that DNA motifs observed in serum are characteristic of RRMS and disease activity and are promising as a clinical tool in monitoring patient responses to treatment modalities.
| S-EPMC2860467 | biostudies-literature
Project description:Stunting, anemia and inflammation are frequently observed in children with end-stage renal disease (ESRD).To assess anthropometric, hematological and inflammatory data and to study their potential interrelationship in Guatemalan juveniles undergoing hemodialysis (HD) and peritoneal dialysis (PD).54 juveniles 7-20 years of age were recruited in FUNDANIER, Guatemala City: 27 on HD and 27 PD. Hemoglobin, serum iron, transferrin, serum transferrin receptor (sTfR), serum ferritin, transferrin saturation and iron-binding capacity, white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), as well as IL-6, IL-1 and TNF-?, weight and height were determined by standard methods. Hepcidin-25 (Hep-25) was assessed by weak cation exchange time-of-flight mass-spectrometry.92% and 55% of HD and PD children, respectively, were stunted and 95% and 85% were anemic. Among iron status biomarkers, serum ferritin was massively increased and significantly higher in the HD group compared to the PD group. Hep-25 was also greatly elevated in both groups. 41% of HD patients showed increments in three or more inflammatory biomarkers, while it was 2 or less in all PD subjects.The degree of stunting, the prevalence and severity of anemia in Guatemalan juvenile ESRD far exceed the national statistics for this low-income Central American country. Ferritin and Hep-25 concentrations were elevated, with the latter to an extraordinary magnitude. Additional biomarkers of inflammation not directly related to iron status were elevated as well. The role of both disease- and environment-related factors in combination best explains the magnitude of the biomarker abnormalities.
| S-EPMC4596869 | biostudies-literature
Project description:Multiple sclerosis (MS) is a life-long, potentially debilitating disease of the central nervous system (CNS). MS is considered to be an immune-mediated disease, and the presence of autoreactive peripheral lymphocytes in CNS compartments is believed to be critical in the process of demyelination and tissue damage in MS. Although MS is not currently a curable disease, several disease-modifying therapies (DMTs) are now available, or are in development. These DMTs are all thought to primarily suppress autoimmune activity within the CNS. Each therapy has its own mechanism of action (MoA) and, as a consequence, each has a different efficacy and safety profile. Neurologists can now select therapies on a more individual, patient-tailored basis, with the aim of maximizing potential for long-term efficacy without interruptions in treatment. The MoA and clinical profile of MS therapies are important considerations when making that choice or when switching therapies due to suboptimal disease response. This article therefore reviews the known and putative immunological MoAs alongside a summary of the clinical profile of therapies approved for relapsing forms of MS, and those in late-stage development, based on published data from pivotal randomized, controlled trials.
| S-EPMC4057629 | biostudies-other
Project description:BackgroundWe examined (1) patient characteristics and disease-modifying drug (DMD) exposure in late-onset (LOMS, ?50 years at symptom onset) versus adult-onset (AOMS, 18-<50 years) MS and (2) the association between interferon-beta (IFN?) and disability progression in older relapsing-onset MS adults (?50 years).MethodsThis retrospective study (1980-2004, British Columbia, Canada) included 358 LOMS and 5627 AOMS patients. IFN?-treated relapsing-onset MS patients aged ?50 (regardless of onset age, 90) were compared with 171 contemporary and 106 historical controls. Times to EDSS 6 from onset and from IFN? eligibility were examined using survival analyses.ResultsLOMS patients (6%) were more likely to be male, with motor onset and a primary-progressive course, and exhibit faster progression and were less likely to take DMDs. Nonetheless, 57% were relapsing-onset, of which 31% were prescribed DMDs, most commonly IFN?. Among older relapsing-onset MS adults, no significant association between IFN? exposure and disability progression was found when either the contemporary (hazard ratio [HR]: 0.46; 95% CI: 0.18-1.22) or historical controls (HR: 0.54; 95% CI: 0.20-1.42) were considered.ConclusionLOMS differed clinically from AOMS. One-third of older relapsing-onset MS patients were prescribed a DMD. IFN? exposure was not significantly associated with reduced disability in older MS patients.
| S-EPMC4397470 | biostudies-literature
Project description:The negative impact of smoking in multiple sclerosis is well established; however, there is much less evidence as to whether smoking cessation is beneficial to progression in multiple sclerosis. Adults with multiple sclerosis registered on the United Kingdom Multiple Sclerosis Register (2011-20) formed this retrospective and prospective cohort study. Primary outcomes were changes in three patient-reported outcomes: normalized Multiple Sclerosis Physical Impact Scale (MSIS-29-Phys), normalized Multiple Sclerosis Walking Scale (MSWS-12) and the Hospital Anxiety and Depression Scale (HADS). Time to event outcomes were clinically significant increases in the patient-reported outcomes. The study included 7983 participants; 4130 (51.7%) of these had ever smoked, of whom 1315 (16.5%) were current smokers and 2815/4130 (68.2%) were former smokers. For all patient-reported outcomes, current smokers at the time of completing their first questionnaire had higher patient-reported outcomes scores indicating higher disability compared to those who had never smoked (∼10 points difference in MSIS-29-Phys and MSWS-12; 1.5-1.8 points for HADS-Anxiety and HADS-Depression). There was no improvement in patient-reported outcomes scores with increasing time since quitting in former smokers. Nine hundred and twenty-three participants formed the prospective parallel group, which demonstrated that MSIS-29-Phys [median (IQR) 5.03 (3.71, 6.34)], MSWS-12 [median (IQR) 5.28 (3.62, 6.94)] and HADS-Depression [median (IQR) 0.71 (0.47, 0.96)] scores worsened over a period of 4 years, whereas HADS-Anxiety remained stable. Smoking status was significant at Year 4; current smokers had higher MSIS-29-Phys and HADS-Anxiety scores [median (IQR) 3.05 (0.22, 5.88) and 1.14 (0.52, 1.76), respectively] while former smokers had a lower MSIS-29-Phys score of -2.91 (-5.03, -0.79). A total of 4642 participants comprised the time to event analysis. Still smoking was associated with a shorter time to worsening event in all patient-reported outcomes (MSIS-29-Phys: n = 4436, P = 0.0013; MSWS-12: n = 3902, P = 0.0061; HADS-Anxiety: n = 4511, P = 0.0017; HADS-Depression: n = 4511, P < 0.0001). Worsening in motor disability (MSIS-29-Phys and MSWS-12) was independent of baseline HADS-Anxiety and HADS-Depression scores. There was no statistically significant difference in the rate of worsening between never and former smokers. When smokers quit, there is a slowing in the rate of motor disability deterioration so that it matches the rate of motor decline in those who have never smoked. This suggests that smoking cessation is beneficial for people with multiple sclerosis.
| S-EPMC9128822 | biostudies-literature
Project description:BackgroundIn this pooled, post hoc analysis of a phase 2 trial and the phase 3 TEMSO, TOWER, and TENERE clinical trials, long-term efficacy and safety of teriflunomide were assessed in subgroups of patients with relapsing multiple sclerosis (MS) defined by prior treatment status.MethodsPatients were classified according to their prior treatment status in the core and core plus extension periods. In the core period, patients were grouped according to treatment status at the start of the study: treatment naive (no prior disease-modifying therapy [DMT] or DMT > 2 years prior to randomization), previously treated with another DMT (DMT > 6 to ≤24 months prior to randomization), and recently treated with another DMT (DMT ≤6 months prior to randomization). In the core plus extension period, patients were re-baselined to the time of starting teriflunomide 14 mg and grouped according to prior treatment status at that time point. Efficacy endpoints included annualized relapse rate (ARR), probability of confirmed disability worsening (CDW) over 12 weeks, and Expanded Disability Status Scale (EDSS) score. The incidence of adverse events was also assessed.ResultsMost frequently received prior DMTs at baseline were glatiramer acetate and interferon beta-1a across treatment groups. Teriflunomide 14 mg significantly reduced ARR versus placebo in the core period, regardless of prior treatment status. In the core and extension periods, adjusted ARRs were low (0.193-0.284) in patients treated with teriflunomide 14 mg across all subgroups. Probability of CDW by Year 4 was similar across subgroups; by Year 5, the percentage of patients with 12-week CDW was similar in treatment-naive patients and patients recently treated with another DMT (33.9 and 33.7%, respectively). EDSS scores were stable over time in all prior-treatment subgroups. There were no new or unexpected safety signals. Limitations include selective bias due to patient attrition, variability in subgroup size, and lack of magnetic resonance imaging outcomes.ConclusionsThe efficacy and safety of teriflunomide 14 mg was similar in all patients with relapsing MS, regardless of prior treatment history.Trial registrationPhase 2 trial core: NCT01487096 ; Phase 2 trial extension: NCT00228163 ; TEMSO core: NCT00134563 ; TEMSO extension: NCT00803049 ; TOWER: NCT00751881 ; TENERE: NCT00883337 .
| S-EPMC7539502 | biostudies-literature
Project description:ObjectiveTo analyse the safety, immunogenicity and factors affecting antibody response to Severe Acute Respiratory Syndrome-Coronavirus-2(SARS-CoV-2) vaccination in patients with systemic sclerosis (SSc).MethodsThis is a phase 4 prospective study within a larger trial of two doses of inactivated SARS-CoV-2 vaccine (CoronaVac) in 51 SSc patients compared with 153 controls. Anti-SARS-CoV-2-IgG and neutralizing antibodies (NAb) were assessed at each vaccine shot (D0/D28) and 6 weeks after the 2nd dose(D69), only in individuals with negative baseline IgG/NAb and those who did not have coronavirus-19(COVID19) during follow-up. Vaccine safety was also assessed in all participants.ResultsPatients and controls had comparable median ages [48(38.5-57) vs 48(38-57) years, p= 0.945]. Patients had mostly diffuse SSc (68.6%) and the majority (74.5%) had interstitial lung disease. Most patients were under immunosuppressive therapy (72.5%), mainly mycophenolate mofetil (MMF) (52.9%). After full vaccination (D69), anti-SARS-CoV-2-IgG frequency (64.1% vs 94.2%, p< 0.001) and NAb positivity (53.8% vs 76.9%; p= 0.006) were moderate, although lower than controls. The first dose response (D28) was low and comparable for both SC (p= 0.958) and NAb positivity (p= 0.537). SSc patients under MMF monotherapy vs other (no therapy/other DMARDs) had lower immunogenicity (SC : 31.3% vs 90%, p< 0.001) and NAb : 18.8% vs 85%, p< 0.001). Multiple regression analysis confirmed that MMF use, but not disease subtype, is associated with insufficient seroconversion [odds ratio (OR)=0.056(95%CI 0.009-0.034), p= 0.002] and NAb positivity [OR = 0.047(95%CI 0.007-0.036), p= 0.002]. No moderate/severe side-effects were observed.ConclusionCoronaVac has an excellent safety profile and moderate response to anti-SARS-CoV-2 vaccine in SSc. Vaccine antibody response is not influenced by disease subtype and is greatly affected by MMF, reinforcing the need for additional strategies to up-modulate vaccine response in this subgroup of patients.Trial registrationClinicalTrials.gov, https://clinicaltrials.gov, NCT04754698.
| S-EPMC8689834 | biostudies-literature
Project description:The multiple sclerosis (MS) patient population is highly heterogeneous in terms of disease course and treatment response. We used a transcriptional profile generated from peripheral blood mononuclear cells to define the structure of an MS patient population. Two subsets of MS subjects (MS(A) and MS(B)) were found among 141 untreated subjects. We replicated this structure in two additional groups of MS subjects treated with one of the two first-line disease-modifying treatments in MS: glatiramer acetate (GA) (n = 94) and interferon-? (IFN-?) (n = 128). One of the two subsets of subjects (MS(A)) was distinguished by higher expression of molecules involved in lymphocyte signaling pathways. Further, subjects in this MS(A) subset were more likely to have a new inflammatory event while on treatment with either GA or IFN-? (P = 0.0077). We thus report a transcriptional signature that differentiates subjects with MS into two classes with different levels of disease activity.
| S-EPMC3753678 | biostudies-literature
Project description:Andropause results from the natural decrease in testosterone levels that occurs with age. In contrast to menopause, which is a universal, well-characterized process associated with absolute gonadal failure, andropause ensues after gradual decline of both hypothalamic-pituitary-gonadal axis activity, as well as of testicular function, a process which usually develops over a period of many years. Increasing evidence on greater risk of Multiple sclerosis (MS) associated with lower testosterone levels is being reported. Likewise, epidemiological studies have shown a later age of onset of MS in men, relative to women, which could perhaps respond to the decline in protective testosterone levels. In this review, we will discuss the role of androgens in the development and function of the innate and adaptive immune response, as well as in neuroprotective mechanisms relevant to MS. Testosterone effects observed in different animal models and in epidemiological studies in humans will be discussed, as well as their correlation with physical disability and cognitive function levels. Finally, published and ongoing clinical trials exploring the role of androgens, particularly at key stages of sexual maturation, will be reviewed.
| S-EPMC8602357 | biostudies-literature