Risk Factor For Multiple Sclerosis Research Articles

Antibiotic Use and Risk of Multiple Sclerosis: A Nested Case-Control Study in Emilia-Romagna Region, Italy

Introduction: Known risk factors for multiple sclerosis (MS) include smoking, a low vitamin D status, obesity, and EBV, while the inflammatory feature of the disease strongly suggests the presence of additional infectious agents. The association between use of antibiotics and MS risk that could shed light on these factors is still undetermined. We aimed to evaluate the association between antibiotics and MS risk, in the Emilia-Romagna region (RER), Italy. Methods: All adult patients with MS seen at any RER MS center (2015–2017) were eligible. For each of the 877 patients included, clinical information was collected and matched to 5 controls (RER residents) (n = 4,205) based on age, sex, place of residence, and index year. Information on antibiotic prescription was obtained through the linkage with the RER drug prescription database. Results: Exposure to any antibiotic 3 years prior to the index year was associated with an increased MS risk (OR = 1.52; 95% CI = 1.29–1.79). Similar results were found for different classes. No dose-response effect was found. Discussion/Conclusions: Our results suggest an association between the use of antibiotics and MS risk in RER population. However, further epidemiological studies should be done with information on early life and lifestyle factors.

Vascular Disease Risk Factors in Multiple Sclerosis (MS) is Associated with Brain Adenosine Triphosphate Abnormalities: Dysmetabolism May Drive MS Disease Progression (2398)

Vascular Disease Risk Factors in Multiple Sclerosis (MS) is Associated with Brain Adenosine Triphosphate Abnormalities: Dysmetabolism May Drive MS Disease Progression (2398)

A Case of Double Standard: Sex Differences in Multiple Sclerosis Risk Factors.

Multiple sclerosis is a complex, multifactorial, dysimmune disease prevalent in women. Its etiopathogenesis is extremely intricate, since each risk factor behaves as a variable that is interconnected with others. In order to understand these interactions, sex must be considered as a determining element, either in a protective or pathological sense, and not as one of many variables. In particular, sex seems to highly influence immune response at chromosomal, epigenetic, and hormonal levels. Environmental and genetic risk factors cannot be considered without sex, since sex-based immunological differences deeply affect disease onset, course, and prognosis. Understanding the mechanisms underlying sex-based differences is necessary in order to develop a more effective and personalized therapeutic approach.

Obesity is associated with the Optic Neuritis severity in Male patients with Multiple Sclerosis

Obesity is an important modifiable risk factor of MS; a deeper biological understanding of this association is needed. To evaluate the determinants of acute optic neuritis (AON) severity and recovery in multiple sclerosis (MS). We included 61 patients with MS with recorded AON severity and recovery according to visual acuity outcomes before, at, and, after the relapse. We measured body mass index (BMI) and the serum concentration of estrogen, leptin, testosterone, sex hormone-binding globulin, and vitamin D. We tested the association between BMI and serum hormones and AON severity and recovery with logistic regressions. In males, moderate/severe AON was associated with higher BMI (31.26 kg/m2 vs 25.73 kg/m2, logistic regression, p= 0.03), higher serum estrogen levels (32.24 nmol/L vs 23.06 nmol/L, logistic regression, p=0.04), and higher serum leptin levels (12.29 ng/mL vs mild AON: 4.1 ng/mL, logistic regression, p=0.06) than mild AON. These observations were not seen in female patients. We did not find an association with BMI or hormone levels and AON recovery. BMI, serum leptin, and serum estrogen were associated with AON severity in male patients but not in female patients. No association of these factors and AON recovery was observed.

Hospital-diagnosed infections before age 20 and risk of a subsequent multiple sclerosis diagnosis

The involvement of specific viral and bacterial infections as risk factors for multiple sclerosis has been studied extensively. However, whether this extends to infections in a broader sense is less clear and little is known about whether risk of a multiple sclerosis diagnosis is associated with other types and sites of infections, such as of the CNS. This study aims to assess if hospital-diagnosed infections by type and site before age 20 years are associated with risk of a subsequent multiple sclerosis diagnosis and whether this association is explained entirely by infectious mononucleosis, pneumonia, and CNS infections. Individuals born in Sweden between 1970-1994 were identified using the Swedish Total Population Register (n = 2,422,969). Multiple sclerosis diagnoses from age 20 years and hospital-diagnosed infections before age 20 years were identified using the Swedish National Patient Register. Risk of a multiple sclerosis diagnosis associated with various infections in adolescence (11-19 years) and earlier childhood (birth-10 years) was estimated using Cox regression, with adjustment for sex, parental socioeconomic position, and infection type. None of the infections by age 10 years were associated with risk of a multiple sclerosis diagnosis. Any infection in adolescence increased the risk of a multiple sclerosis diagnosis (hazard ratio 1.33, 95% confidence interval 1.21-1.46) and remained statistically significant after exclusion of infectious mononucleosis, pneumonia, and CNS infection (hazard ratio 1.17, 95% confidence interval 1.06-1.30). CNS infection in adolescence (excluding encephalomyelitis to avoid including acute disseminated encephalitis) increased the risk of a multiple sclerosis diagnosis (hazard ratio 1.85, 95% confidence interval 1.11-3.07). The increased risk of a multiple sclerosis diagnosis associated with viral infection in adolescence was largely explained by infectious mononucleosis. Bacterial infections in adolescence increased risk of a multiple sclerosis diagnosis, but the magnitude of risk reduced after excluding infectious mononucleosis, pneumonia and CNS infection (hazard ratio 1.31, 95% confidence interval 1.13-1.51). Respiratory infection in adolescence also increased risk of a multiple sclerosis diagnosis (hazard ratio 1.51, 95% confidence interval 1.30-1.75), but was not statistically significant after excluding infectious mononucleosis and pneumonia. These findings suggest that a variety of serious infections in adolescence, including novel evidence for CNS infections, are risk factors for a subsequent multiple sclerosis diagnosis, further demonstrating adolescence is a critical period of susceptibility to environmental exposures that raise the risk of a multiple sclerosis diagnosis. Importantly, this increased risk cannot be entirely explained by infectious mononucleosis, pneumonia, or CNS infections.

DRB1–environment interactions in multiple sclerosis etiology: results from two Swedish case–control studies

ObjectiveWe aimed to investigate the influence of environmental risk factors for multiple sclerosis (MS) in different genetic contexts, and study if interactions between environmental factors and human leucocyte antigen (HLA)...

Shared breastfeeding & other early multiple sclerosis risk factors: A case-control study

Background: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease. Etiology is thought to be multifactorial with genetic and environmental factors interplay. Our objective in this study is to evaluate culture specific and other early life risk factors for MS. We examined the association between MS and breastfeeding including shared breastfeeding, parental consanguinity, being born abroad or living abroad during childhood, prematurity, vaccination, tonsillectomy, rank among siblings, number of siblings, number of household members (HHM) at birth, and age first time joining school.Methods: This is an age and sex matched case-control study that was conducted in Riyadh, Kingdom of Saudi Arabia (KSA). We enrolled 300 cases and 601 controls. A structured questionnaire about demographics, consanguinity and potential environmental factors was answered by participants. Data was analyzed using logistic regression adjusting for covariates occurring later in life such as waterpipe smoking and performing Hajj.Results: About two thirds of the cases and the controls were females. Mean age was 34.8 (9.2) for the cases and 33.6 (10.6) for the controls. We found that shared breastfeeding (OR=0.58; 95% CI, 0.35-0.96, p = 0.033), and older age first joining school (OR=0.83; 95% CI, 0.73-0.94, p = 0.005) were associated with decrease risk of MS. While longer duration of breastfeeding by biological mother (OR=1.03; 95% CI, 1.01-1.04, p = 0.001), rank among siblings of ≥6 (OR=1.69; 95% CI, 1.11-2.56, p = 0.014), and larger number of HHM at birth (OR=2.32; 95% CI, 1.64-3.28, p = 0.001) were associated with increased risk. Patients with MS were less likely to receive formula with breastfeeding than controls (OR=0.72; 95% CI, 0.51-0.99, p = 0.046). No association was found with breastfeeding by biological mother, number of siblings, prematurity, being born abroad or living abroad during childhood, vaccination, consanguinity, or tonsillectomy.Conclusion: The findings of this case-control study add to the accumulating evidence that early life factors could modify the risk of developing MS. Among these, novel associations with shared breastfeeding and number of HHM at birth are suggested. Future studies are needed to verify the observed results.

Prognostic factors for relapse and outcome in pediatric acute transverse myelitis

ObjectiveIt may be difficult for clinicians to estimate the prognosis of pediatric acute transverse myelitis (ATM). The aim of this study was to define prognostic factors for relapsing disease and poor outcome in pediatric ATM. MethodsThis prospective cohort study included 49 children, 18 boys and 31 girls (median age 13.1 years, IQR 6.5–16.2) with a first episode of ATM. Factors associated with relapsing disease and poor outcome (Expanded Disability Status Scale (EDSS) ≥ 4) were assessed during a median follow-up of 37 months (IQR 18–75). ResultsIn total, 14 patients (29%) experienced ≥ 1 relapse(s) and nine patients (18%) had a poor outcome. Factors at onset associated with relapsing disease included higher age (16.1 vs. 11.6 years, p = 0.002), longer time to maximum severity of symptoms (5.5 vs. 3 days, p = 0.01), lower maximum EDSS score (4.0 vs. 6.5, p = 0.003), short lesion on spinal MRI (64 vs. 21%, p = 0.006), abnormalities on brain MRI (93 vs. 44%, p = 0.002) and presence of oligoclonal bands in cerebrospinal fluid (67 vs. 14%, p = 0.004). The only factor associated with poor outcome was presence of a spinal cord lesion on MRI without cervical involvement (56 vs. 14%, p = 0.02). ConclusionPediatric ATM patients presenting with clinical, radiological and laboratory features associated with multiple sclerosis (MS) are at risk for relapsing disease. In absence of these known MS risk factors at onset of disease these patients are at low risk for relapses. Only a minority of pediatric ATM patients in this cohort have a poor outcome.

Contribution of hsa-miR-146a and hsa-miR-223 gene variations in patients with multiple sclerosis reveals association of rs2910164 and rs1044165 with risk of multiple sclerosis susceptibility

MicroRNAs (miRNAs) are a group of non-coding RNAs that play a role in gene regulation. Due to their possible functional importance, genetic variants within miRNA genes have been recognized as...

Serum vitamin d inversely correlates with depression scores in people with multiple sclerosis

BackgroundVitamin D (Vit.D) deficiency is a risk factor for multiple sclerosis (MS) and correlates with its severity. Depression is also common in people with MS (PWMS). We aim to investigate Vit.D correlation with depression risk scores in PWMS. MethodsA cross-sectional cohort of PWMS were studied. Clinical and demographic data were collected. The Hospital Anxiety Depression Scale (HADS) and the Beck Depression Inventory-II (BDI-II) were used to evaluate the risk of depression. Expanded Disability Status Scale (EDSS) and Patient Determined Disease Steps (PDDS) were used to evaluate the disability. Serum concentrations of 25-hydroxyvitamin D were measured. Bivariate and partial correlations of Vit.D status and scores of depressive and disability scales were statistically analyzed. The IBM Statistical Package for Social Sciences software, version 25.0, was used for data processing. ResultsA total of 88 PWMS were enrolled. More than half of them had potential depression, and 68% had below-normal serum Vit.D levels (normal ≥ 30 ng/ml, insufficient = 21–29 ng/ml, and deficient ≤ 20 ng/ml). Serum Vit.D levels significantly correlated with scores of depression scales in both males and females, which was more robust in males. This association was maintained with a partial correlation analysis controlling for age, sex, body mass index, disease duration, type of MS, and EDDS HADS: r=-0.513, p<0.001; BDI-II: r=-0.401, p<0.001). Serum Vit.D had significant inverse correlations with EDSS score (r=-0.353, p = 0.001) and PDDS score (r=-0.341, p = 0.001), with more robust correlations in females compared to the whole group. ConclusionVit.D levels correlate with depression risk scores in PWMS with differential sex effects.

Risk factors of multiple sclerosis in Aseer region, Kingdom of Saudi Arabia A case-control study.

Objectives:To investigate socio-demographic and environmental risk factors of multiple sclerosis (MS) in Aseer region, Kingdom of Saudi Arabia (KSA).Methods:This was a retrospective, record, and interview based matched case control study completed in the neurology clinics at tertiary hospitals in Aseer, KSA. It included 82 MS cases and 82 controls. The study used a structured questionnaire to collect information on key socio-demographic and environmental exposures. The main outcome measure was a statistically significant relationship of key socio-demographic and environmental risk factors with MS.Results:A total of 82 registered patients, 50 were females, resulting in a female to male ratio of 1.56:1. Various risk factors were found to have a statistically significant association with MS which included female (OR=3.01, 95% CI [1.59:5.69]; p<0.001), family history of MS (OR=2.1, 95%CI [2.4:1.7] p=0.04), low exposure to sunlight (OR=2.02, 95%CI [2.53: 9.9] p<0.001), only fed breast milk in childhood (OR=0.46, 95%CI [0.55:0.39]; p<0.001), parental consanguinity (OR=2.17 95%CI [4.11:1.14] p=0.017), history of chickenpox (OR=15.59 95% CI [68.7:3.55]; p<0.01). On using multiple logistic regression, chicken pox infection (AOR=0.045, 95%CI [0.015-0.135]; p=0.001)and low sun-exposure (AOR=.271, 95%CI [.121-.609]; p<0.05) were deduced as the predictors of MS in this region.Conclusion:This study offers unique insights into the risk factors of MS. Low sun exposure and childhood chickenpox are significantly related to the development of MS in the Aseer region.

Multiple sclerosis in Iran: An epidemiological update with focus on air pollution debate’

Multiple sclerosis (MS), as the most common neurologic disorder of the central nervous system, with growing incidence and prevalence worldwide and in the Middle East. This article aimed to find out the potential relationship between MS and air pollution in Iran. By assessing the published articles on MS and air pollution in Iran, the situation of MS as well as air/soil pollution in Iran was clarified. Then, studies on air pollution and its potential effect on Iranian MS patients were checked until 2020. The MS prevalence is distributed across Iran Provinces with highest rates in Isfahan, located in the center of Iran. The higher rates of MS in Isfahan and Tehran (the Metropolitan) might be due to industrial pollution of these cities, but this hypothesis is not true for non-industrial provinces. Based on the published atlas of MS in Iran, it seems that there is a high-risk "belt" from northwest to southeast. There are many risk factors of MS in Iran including age, gender, Vitamin D deficiency, smoking, and air pollution. The potential main risk factor of MS might be air pollution considering Isfahan and Tehran provinces. However, Chahar Mahal and Bakhtiary Province, with non-industrial nature, has the second highest MS rates which does not follow this hypothesis. By finding the air pollution as the main potential risk factor of MS in big provinces including Isfahan and Tehran, its effect of this factor can also be considered during diagnosis and treatment.

Risk factors for multiple sclerosis in the Kabardino-Balkar Republic

To study the features of the representation of risk factors for the development of multiple sclerosis (MS) in the Kabardino-Balkar Republic (KBR). The results of the examination and follow - up of patients with MS for 5 years (2012-2015) living in two regions of the CBD-Nalchik and the Prokhladnensky district-were analyzed. For the diagnosis of MS, the McDonald criteria (2010) were used, and the EDSS scale was used to assess the severity of invalidization. Registration of risk factors for the development of MS was carried out on the basis of a unified questionnaire. The diagnosis of MS was established based on the criteria of I. MacDonald (2017). Contact with potentially dangerous chemical compounds, consumption of smoked meat products, and a history of viral infections were significantly more common in residents of the Prokhladnensky district (all differences were significant, p<0.05). Patients with MS were more likely to have suffered from scarlatina (n=23; 19.5% and n=14; 13.4%, 95% CI 0.43 (0.32-1.01), patients with scarlet fever after the age of 15 years (n=7; 6.3% and n=1; 0.9%, 95% CI 2.45 (1.92-3.21), p=0.041). Also, in the main group, patients with chickenpox were more common (n=70; 62.5% and n=55; 41.1%; 95% CI 0.78 (0.65-0.94, p=0.032), while the closest association of chickenpox and MS development occurred in patients of the main group who had the disease at the age of 7 years (p=0.041).

DNA Methylation As an Epigenetic Mechanism in the Development of Multiple Sclerosis.

The epigenetic mechanisms of gene expression regulation are a group of the key cellular and molecular pathways that lead to inherited alterations in genes’ activity without changing their coding sequence. DNA methylation at the C5 position of cytosine in CpG dinucleotides is amongst the central epigenetic mechanisms. Currently, the number of studies that are devoted to the identification of methylation patterns specific to multiple sclerosis (MS), a severe chronic autoimmune disease of the central nervous system, is on a rapid rise. However, the issue of the contribution of DNA methylation to the development of the different clinical phenotypes of this highly heterogeneous disease has only begun to attract the attention of researchers. This review summarizes the data on the molecular mechanisms underlying DNA methylation and the MS risk factors that can affect the DNA methylation profile and, thereby, modulate the expression of the genes involved in the disease’s pathogenesis. The focus of our attention is centered on the analysis of the published data on the differential methylation of DNA from various biological samples of MS patients obtained using both the candidate gene approach and high-throughput methods.

Association of Multiple Sclerosis with PM 2.5 levels. Further evidence from the highly polluted area of Padua Province, Italy

BackgroundFifty years of epidemiological survey and intra-regional differences in prevalence suggest that environmental factors may be associated with increased multiple sclerosis (MS) risk in Northern Italy. Based on the findings of a previous study carried out in the highly polluted Padan Plain, we further explored the relationship between PM2.5 levels and MS prevalence by comparing bordering areas characterized by quite different environmental conditions, namely the Municipality of Padua and the special protected zone (SPZ) of the Euganean Hills Regional Park, located 15 km from the City. MethodsThree territories were identified; 1) the SPZ, extending over an area of 15.096 hectares and having a total population of 23,980 inhabitants, 2) the urban area of Padua, with a total population of 210,440 inhabitants and repeatedly recognized by the European Invironmental Agency as one of the most polluted Cities of Europe, 3) the Intermediate Zone (IZ), i.e., the area in between the previous two, including part of the urban territories of eight villages adjacent to the SPZ. Demographic and socio-economical data were obtained from official government sources (www.istat.it and www.regione.veneto.it). All Italian MS patients residing in these three areas on December 31, 2018, were registered. PM2.5 concentrations (annual average 1998–2018, μg/m3) were measured by satellite. The correlation between PM2.5 concentrations and MS prevalence was analysed. ResultsMS prevalence was significantly higher in Padua City (265/100.000) compared to both the SPZ of the Euganean Hills Park (160/100,000; p < 0.0001) and the IZ (194.4/100,000). Prevalence strongly associated with the annual average concentration of PM2.5 (r = 0.89 p < 0.00001). ConclusionIn the Province of Padua, one of the most polluted areas of Europe, MS prevalence is strongly associated with PM2.5 exposure. Our findings suggest that air pollutants may be one of the possible environmental risk factors for MS in the Veneto Region of Italy.

Epstein-Barr virus infection after adolescence and human herpesvirus 6A as risk factors for multiple sclerosis.

Background and purposeInfections with human herpesvirus 6A (HHV‐6A) and Epstein–Barr virus (EBV) have been linked to multiple sclerosis (MS) development. For EBV, late infection has been proposed as a risk factor, but serological support is lacking. The objective of this study was to investigate how age affects the EBV and HHV‐6A associated risks of developing MS.MethodsIn this nested case–control study, Swedish biobanks were accessed to find pre‐symptomatically collected blood samples from 670 individuals who later developed relapsing MS and 670 matched controls. A bead‐based multiplex assay was used to determine serological response against EBV and HHV‐6A. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals.ResultsSeropositivity against EBV exhibited a pattern where associations switched from a decreased risk of developing MS in the group below 20 years of age to an increased risk amongst individuals aged 20–29 and 30–39 years (p for trend 0.020). The age of transition was estimated to be 18.8 years. In contrast, HHV‐6A was associated with increased MS risk in all age groups (total cohort odds ratio 2.1, 95% confidence interval 1.6–2.7).ConclusionsThis study suggests EBV infection after adolescence and age independent HHV‐6A infection as risk factors for MS.

Pomegranate peel extract ameliorates the severity of experimental autoimmune encephalomyelitis via modulation of gut microbiota

ABSTRACT Multiple sclerosis (MS) is a CNS autoimmune disease characterized by demyelination and inflammatory infiltration with a high disability rate. Increasing evidence has demonstrated the importance of gut microbiota as an environmental risk factor in MS and its animal model experimental autoimmune encephalomyelitis (EAE). Diet is the main determinant of gut microbiota composition and function, which greatly affects the shaping of microbial structure. Pomegranate peel, a waste product in the production of juice, is rich in health-promoting compounds. However, its individual constituents, immunoregulatory activities, and action associated with bacterial diversity in the gut microbiota are largely unknown. Here, the main nutrient ingredients of pomegranate peel extract (PPE) were identified as phenols, flavonoids, amino acids, carbohydrates, fatty acids, lipids, nucleotides, organic acids, alcohols, and vitamins via metabolomics evaluation. We found, for the first time, oral PPE (100 mg/kg/day) not only effectively relieves EAE, inhibits CNS inflammatory factor infiltration and myelin loss, but also reshapes gut microbiota. Furthermore, recipient EAE mice with fecal transplantation from the PPE-treated donor delayed the disease development significantly. 16S rRNA gene sequencing revealed the increased gut microbiota richness in PPE-treated group. Among them, Lactobacillaceae enriched significantly, while Alcaligenaceae and Acidaminococcacea decreased remarkably. In conclusion, our data demonstrated that gut microbiota mediated the beneficial effects of oral PPE on EAE, and provided new ideas for developing the prebiotic value of pomegranate peel for the treatment of autoimmune diseases.

Air pollution as a contributor to the inflammatory activity of multiple sclerosis

ObjectiveAir pollution has been recently identified as a risk factor for multiple sclerosis. Aim of this study was to investigate the immunological mechanism underlying the clinical association between air pollution, namely exposure to particulate matter 10 (PM10), and inflammatory activity of multiple sclerosis (MS)MethodsDaily recording of PM10 was obtained by monitors depending on the residence of subjects. Expression of molecules involved in activation, adhesion, and migration of T lymphocytes were tested by flow cytometry in 57 MS patients and 19 healthy controls. We next assessed in vitro the effect of PM10 on expression of C-C chemokine receptors 6 (CCR6) by peripheral blood mononuclear cells (PBMCs), on cytokine production by monocyte-derived dendritic cells (mdDC), and on T cell polarization in PBMC/mdDC mixed cultures.ResultsWe identified a significant correlation between mean PM10 levels and expression of CCR6 CD4+ T circulating cells in MS patients. This was paralleled by the observation in vitro of a higher level of CCR6 expression on PBMC following treatment with increased doses of particulate matter. Moreover, in mdDC cultures, particulate matter induced the secretion by mdDC of Th17 polarizing IL1 beta, IL6, and IL23 and, in mdDC/PBMC mixed cultures, enhanced generation of IL17-producing T cells.ConclusionsEx vivo and in vitro studies support the pro-inflammatory role of PM in MS, by upregulating expression of CCR6 on circulating CD4+ T cells and inducing in innate immune cells the production of Th17 polarizing cytokines. Therefore, we speculate that in MS respiratory exposure to PM10 may induce the production in the lung of autoreactive Th17 lymphocytes and boost their migratory properties through the blood-brain barrier.

Attenuated immune control of Epstein-Barr virus in humanized mice is associated with the multiple sclerosis risk factor HLA-DR15.

Immune responses to Epstein-Barr virus (EBV) infection synergize with the main genetic risk factor HLA-DRB1*15:01 (HLA-DR15) to increase the likelihood to develop the autoimmune disease multiple sclerosis (MS) at least sevenfold. In order to gain insights into this synergy, we investigated HLA-DR15 positive human immune compartments after reconstitution in immune-compromised mice (humanized mice) with and without EBV infection. We detected elevated activation of both CD4+ and CD8+ T cells in HLA-DR15 donor-reconstituted humanized mice at steady state, even when compared to immune compartments carrying HLA-DRB1*04:01 (HLA-DR4), which is associated with other autoimmune diseases. Increased CD8+ T cell expansion and activation was also observed in HLA-DR15 donor-reconstituted humanized mice after EBV infection. Despite this higher immune activation, EBV viral loads were less well controlled in the context of HLA-DR15. Indeed, HLA-DR15-restricted CD4+ T cell clones recognized EBV-transformed B cell lines less efficiently and demonstrated cross-reactivity toward allogeneic target cells and one MS autoantigen. These findings suggest that EBV as one of the main environmental risk factors and HLA-DR15 as the main genetic risk factor for MS synergize by priming hyperreactive T-cell compartments, which then control the viral infection less efficiently and contain cross-reactive CD4+ T cell clones.

Early postnatal tobacco smoke exposure aggravates experimental autoimmune encephalomyelitis in adult rats

Although substantial evidence supports smoking as a risk factor for the development of multiple sclerosis (MS) in adulthood, it remains controversial whether early-life exposure to environmental tobacco smoke (ETS) increases the risk of MS later in life. Here, using experimental autoimmune encephalomyelitis (EAE) as an animal model for MS, we show that exposing neonatal rats during the first week (ETS1-EAE), but not the second week (ETS2-EAE) and the third week (ETS3-EAE) after birth, increased the severity of EAE in adulthood in comparison to pups exposed to filtered compressed air (AIR-EAE). The ETS1-EAE rats showed a worse neurological deficit score and a significant increase in CD4+ cell infiltration, demyelination, and axonal injury in the spinal cord compared to AIR-EAE, ETS2-EAE, and ETS3-EAE groups. Flow cytometry analysis showed that the ETS1 group had decreased numbers of regulatory T (Treg) cells and increased effector T (Teff) cells in the brain and spinal cord. The expressions of Treg upstream regulator Foxp3 and downstream cytokines such as IL-10 were also altered accordingly. Together, these findings demonstrate that neonatal ETS exposure suppresses Treg functions and aggravates the severity of EAE, confirming early-life exposure to ETS as a potential risk factor for multiple sclerosis in adulthood.