The genetic diversity of multiple sclerosis risk among Hispanic and African American populations living in the United States.

BACKGROUND: Substantial progress has been made toward unraveling the genetic architecture of multiple sclerosis (MS) within populations of European ancestry, but few genetic studies have focused on Hispanic and African American populations within the United States. OBJECTIVE: We sought to test the relevance of common European MS risk variants outside of the major histocompatibility complex (n = 200) within these populations. METHODS: Genotype data were available on 2652 Hispanics (1298 with MS, 1354 controls) and 2435 African Americans (1298 with MS, 1137 controls). We conducted single variant, pathway, and cumulative genetic risk score analyses. RESULTS: We found less replication than statistical power suggested, particularly among African Americans. This could be due to limited correlation between the tested and causal variants within the sample or alternatively could indicate allelic and locus heterogeneity. Differences were observed between pathways enriched among the replicating versus all 200 variants. Although these differences should be examined in larger samples, a potential role exists for gene-environment or gene-gene interactions which alter phenotype differentially across racial and ethnic groups. Cumulative genetic risk scores were associated with MS within each study sample but showed limited diagnostic capability. CONCLUSION: These findings provide a framework for fine-mapping efforts in multi-ethnic populations of MS.

Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study.

OBJECTIVE: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). METHODS: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. RESULTS: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. CONCLUSION: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS.

Cognitive impairment in early stages of multiple sclerosis is associated with high cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain.

BACKGROUND AND PURPOSE: Chitinase 3-like 1 (CHI3L1) and neurofilament light chain (NF-L) are promising biomarkers of disability in multiple sclerosis (MS). However, their role in cognitive dysfunction remains elusive. Here, we aimed to correlate cerebrospinal fluid (CSF) levels of CHI3L1 and NF-L with cognitive status in MS. METHODS: Fifty one recently diagnosed patients were cognitively evaluated and CSF was collected. Levels of CHI3L1 and NF-L were determined by ELISA. Spearman's partial correlation coefficient was performed. RESULTS: After adjusting cognitive scores by age, anxiety and EDSS, association was detected between CHI3L1 levels and Trail Making Test A (rs = 0.348; p = 0.016) and between NF-L levels and Word List Generation (rs = -0.324; p = 0.025). CONCLUSION: High levels of CSF CHI3L1 and NF-L are associated with cognitive impairment in the early phases of MS.

Response to interferon-beta treatment in multiple sclerosis patients: a genome-wide association study.

Up to 50% of multiple sclerosis (MS) patients do not respond to interferon-beta (IFN-ß) treatment and determination of response requires lengthy clinical follow-up of up to 2 years. Response predictive genetic markers would significantly improve disease management. We aimed to identify IFN-ß treatment response genetic marker(s) by performing a two-stage genome-wide association study (GWAS). The GWAS was carried out using data from 151 Australian MS patients from the ANZgene/WTCCC2 MS susceptibility GWAS (responder (R)=51, intermediate responders=24 and non-responders (NR)=76). Of the single-nucleotide polymorphisms (SNP) that were validated in an independent group of 479 IFN-ß-treated MS patients from Australia, Spain and Italy (R=273 and NR=206), eight showed evidence of association with treatment response. Among the replicated associations, the strongest was observed for FHIT (Fragile Histidine Triad; combined P-value 6.74 × 10-6) and followed by variants in GAPVD1 (GTPase activating protein and VPS9 domains 1; combined P-value 5.83 × 10-5) and near ZNF697 (combined P-value 8.15 × 10-5).

Significant clinical worsening after natalizumab withdrawal: Predictive factors.

We aimed to single out multiple sclerosis (MS) cases with poor outcome after natalizumab withdrawal and to identify predictive variables. We ascertained 47 withdrawals, and compared their pre- and post-natalizumab periods. We objectively defined significant clinical worsening after natalizumab withdrawal as a 2-step increase in Expanded Disability Status Scale (EDSS). We performed regression models. As a group, post-natalizumab annualized relapse rate (ARR) was lower in the post-natalizumab period, and there were no differences in the mean number of gadolinium (Gd)-enhancing lesions between pre- and post-natalizumab magnetic resonance imaging (MRI). Corticosteroid treatment did not change the outcomes. Eight patients (19%) presented significant clinical worsening after natalizumab withdrawal, which was predicted by a higher baseline EDSS and a 1-step EDSS increase while on natalizumab.

Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study.

BACKGROUND AND OBJECTIVE: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. METHODS: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. RESULTS: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. CONCLUSIONS: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.

Early detection of neutralizing antibodies to interferon-beta in multiple sclerosis patients: binding antibodies predict neutralizing antibody development.

BACKGROUND: Neutralizing antibodies (NAb) affect efficacy of interferon-beta (IFN-b) treatment in multiple sclerosis (MS) patients. NAbs evolve in up to 44% of treated patients, usually between 6-18 months on therapy. OBJECTIVES: To investigate whether early binding antibody (BAb) titers or different IFN-b biomarkers predict NAb evolution. METHODS: We included patients with MS or clinically isolated syndrome (CIS) receiving de novo IFN-b treatment in this prospective European multicenter study. Blood samples were collected at baseline, before and after the first IFN-b administration, and again after 3, 12 and 24 months on that therapy; for determination of NAbs, BAbs, gene expression of MxA and protein concentrations of MMP-9, TIMP-1, sTRAIL, CXCL-10 and CCL-2. RESULTS: We found that 22 of 164 (13.4%) patients developed NAbs during a median time of 23.8 months on IFN-b treatment. Of these patients, 78.9% were BAb-positive after 3 months. BAb titers ≥ 1:2400 predicted NAb evolution with a sensitivity of 74.7% and a specificity of 98.5%. Cross-sectionally, MxA levels were significantly diminished in the BAb/NAb-positive samples; similarly, CXCL-10 and sTRAIL concentrations in BAb/NAb-positive and BAb-positive/NAb-negative samples, respectively, were also diminished compared to BAb/NAb-negative samples. CONCLUSIONS: BAb titers reliably predict NAbs. CXCL-10 is a promising sensitive biomarker for IFN-b response and its abrogation by anti-IFN-b antibodies.

Cellular immune responses in multiple sclerosis patients treated with interferon-beta.

We investigated cellular immune responses at baseline in peripheral blood mononuclear cells (PBMC) of patients with multiple sclerosis (MS) treated with interferon (IFN)-ß and classified into responders and non-responders according to clinical response criteria. Levels for IFN-γ, interleukin (IL)-17A, IL-17F, IL-10 and IL-4 were determined in activated PBMC of 10 responders, 10 non-responders and 10 healthy controls by cytometric bead arrays. Cytokine levels in cell culture supernatants were similar between responders and non-responders, and comparable to those obtained in healthy controls. These findings do not support differential cellular immune responses in PBMC at baseline between IFN-ß responders and non-responders.

SIGLEC1 and SIGLEC7 expression in circulating monocytes of patients with multiple sclerosis.

BACKGROUND: Sialic acid binding immunoglobulin-like lectins (Siglecs) are cell surface receptors that recognize sialic acids and may attenuate immune responses and reduce inflammation. OBJECTIVE: The purpose of this study was to investigate the role of two members of the Siglec family, SIGLEC1 and SIGLEC7, in the clinical course and disease activity of patients with multiple sclerosis (MS). METHODS: SIGLEC1 and SIGLEC7 expression was determined by flow cytometry in the blood monocytes of 16 healthy controls and 55 untreated MS patients (13 primary progressive MS (PPMS) patients, 13 secondary progressive MS (SPMS) patients and 29 relapsing-remitting MS (RRMS) patients (18 during clinical remission and 11 during relapse)). RESULTS: SIGLEC1 expression by CD14+ monocytes was significantly increased in MS patients compared with controls (p=0.025 for percentage of positive cells; p=0.007 for mean fluorescence intensity (MFI)). Stratification of patients into different clinical forms revealed increased SIGLEC1 expression in patients with progressive forms of the disease, particularly in those with PPMS (p=0.003 for percentage of positive cells and p=0.001 for MFI when compared with controls; p=0.031 for percentage of positive cells when compared with RRMS patients). Both inflammatory and resident monocytes contributed to the increase in SIGLEC1 expression observed in PPMS patients. SIGLEC7 expression was significantly up-regulated in blood monocytes from RRMS during relapse compared with patients during clinical remission (p=0.001 for MFI). CONCLUSIONS: These findings suggest roles for SIGLEC1 in the chronic progressive phases of MS and for SIGLEC7 in acute disease activity.

Roles of the ubiquitin peptidase USP18 in multiple sclerosis and the response to interferon-ß treatment.

BACKGROUND AND PURPOSE: Ubiquitin specific peptidase 18 (USP18) is a deubiquitinating enzyme that functions as a negative regulator of the type I interferon (IFN) signalling pathway and is specifically induced by type I IFNs. In the present study, previous observations by our group were expanded suggesting an implication of USP18 in multiple sclerosis (MS) based on the finding of a deficient expression of the gene in peripheral blood mononuclear cells from MS patients compared with healthy controls. METHODS: Two polymorphisms, rs2542109 (intronic) and rs9618216 (promoter), were genotyped in a cohort of 691 relapse-onset MS patients and 1028 healthy controls and in 225 MS patients treated with IFNß and classified into responders and non-responders after 2 years of treatment according to clinical criteria. Correlations between genotypes and expression levels for USP18 and its target ISG15 were performed by real-time polymerase chain reaction. RESULTS: Two USP18 haplotypes were significantly associated with MS, TG and CG. Additional experiments revealed that CG carriers were characterized by lower USP18 gene expression levels in peripheral blood mononuclear cells and higher clinical disease activity. Finally, AA homozygosis for the intronic polymorphism rs2542109 was associated with the responder phenotype; however, USP18 expression levels induced by IFNß did not differ amongst MS patients carrying different rs2542109 genotypes. CONCLUSIONS: Altogether, these results point to a role of USP18 in MS pathogenesis and the therapeutic response to IFNß.

A cytokine gene screen uncovers SOCS1 as genetic risk factor for multiple sclerosis.

Cytokine and cytokine receptor genes, including IL2RA, IL7R and IL12A, are known risk factors for multiple sclerosis (MS). Excitotoxic oligodendroglial death mediated by glutamate receptors contributes to demyelinating reactions. In the present study, we screened 368 single-nucleotide polymorphisms (SNPs) in 55 genes or gene clusters coding for cytokines, cytokine receptors, suppressors of cytokine signaling (SOCS), complement factors and glutamate receptors for association with MS in a Spanish-Basque resident population. Top-scoring SNPs were found within or nearby the genes coding for SOCS-1 (P=0.0005), interleukin-28 receptor, alpha chain (P=0.0008), oncostatin M receptor (P=0.002) and interleukin-22 receptor, alpha 2 (IL22RA2; P=0.003). The SOCS1 rs243324 variant was validated as risk factor for MS in a separate cohort of 3919 MS patients and 4003 controls (combined Cochran-Mantel-Haenszel P=0.00006; odds ratio (OR)=1.13; 95% confidence interval (CI)=1.07-1.20). In addition, the T allele of rs243324 was consistently increased in relapsing-remitting/secondary progressive versus primary-progressive MS patients, in each of the six data sets used in this study (P(CMH)=0.0096; OR=1.24; 95% CI 1.05-1.46). The association with SOCS1 appears independent from the chr16MS risk locus CLEC16A.

ANKRD55 and DHCR7 are novel multiple sclerosis risk loci.

Multiple sclerosis (MS) shares some risk genes with other disorders hallmarked by an autoimmune pathogenesis, most notably IL2RA and CLEC16A. We analyzed 10 single-nucleotide polymorphisms (SNPs) in nine risk genes, which recently emerged from a series of non-MS genome-wide association studies (GWAS), in a Spanish cohort comprising 2895 MS patients and 2942 controls. We identified two SNPs associated with MS. The first SNP, rs6859219, located in ANKRD55 (Chr5), was recently discovered in a meta-analysis of GWAS on rheumatoid arthritis (RA), and emerged from this study with genome-wide significance (odds ratio (OR) = 1.35; P = 2.3 × 10(-9)). The second SNP, rs12785878, is located near DHCR7 (Chr11), a genetic determinant of vitamin D insufficiency, and showed a size effect in MS similar to that recently observed in Type 1 diabetes (T1D; OR = 1.10; P = 0.009). ANKRD55 is a gene of unknown function, and is flanked proximally by the IL6ST-IL31RA gene cluster. However, rs6859219 did not show correlation with a series of haplotype-tagging SNPs covering IL6ST-IL31RA, analyzed in a subset of our dataset (D'< 0.31; r(2)< 0.011). Our results expand the number of risk genes shared between MS, RA and T1D.

Chitinase 3-like 1 plasma levels are increased in patients with progressive forms of multiple sclerosis.

BACKGROUND: Chitinase 3-like 1 (CHI3L1) is upregulated in a wide variety of inflammatory conditions. Recent studies have pointed to a role of CHI3L1 in multiple sclerosis (MS) pathogenesis. OBJECTIVE: The objective of this study was to investigate the role of plasma CHI3L1 in MS clinical course and disease activity and to evaluate the effect of interferon-beta (IFNß) treatment on protein levels. METHODS: Plasma CHI3L1 levels were determined by ELISA in 57 healthy controls (HC), 220 untreated MS patients [66 primary progressive MS patients (PPMS), 30 secondary progressive MS patients (SPMS), and 124 relapsing-remitting MS patients (RRMS), 94 during clinical remission and 30 during relapse], and 32 MS patients receiving IFNß treatment. A polymorphism of the CHI3L1 gene, rs4950928, was genotyped in 3274 MS patients and 3483 HC. RESULTS: Plasma CHI3L1 levels were significantly increased in patients with progressive forms of MS compared with RRMS patients and HC. CHI3L1 levels were similar between RRMS patients in relapse and remission. A trend towards decreased CHI3L1 levels was observed in IFNß-treated patients. Allele C of rs4950928 was significantly associated with PPMS patients and with higher plasma CHI3L1 levels. CONCLUSIONS: These findings point to a role of CHI3L1 in patients with progressive forms of MS, particularly in those with PPMS.

Change in the clinical activity of multiple sclerosis after treatment switch for suboptimal response.

BACKGROUND: Therapy for multiple sclerosis (MS) has a partial efficacy, and a significant proportion of treated patients will develop a suboptimal response with first-line disease-modifying drugs (DMD). Therapy switch in patients with MS can be a strategy after a treatment failure. We studied the change in clinical activity after switching of first-line DMD because of a treatment failure. METHODS: Relapsing-remitting multiple sclerosis (RRMS) patients treated with interferon-beta (IFNB) or glatiramer acetate (GA) were divided into (i) patients without change in DMD, (ii) patients with a change in DMD because of a poor response, and (iii) those with a change in DMD without relation with response. Annualized relapse rate (ARR) and relapse-free proportions were analyzed. RESULTS: We identified 923 patients with RRMS. Of the 180 who experienced a change because of suboptimal response, 90 switched to another first-line DMT, 38 to mitoxantrone, and 52 to natalizumab. Median ARR in the pre-DMD period on first DMD and second DMD was the following: 1, 1, and 0 for switchers from IFNB to another IFNB (P = 0.0001); 0.67, 1, and 0 for switchers from GA to IFNB (P = 0.01); 1, 1, and 0 for switchers from an IFNB to GA (P = 0.02); 1.1, 1.5, 0.2 for switchers from IFNB or GA to mitoxantrone (P = 0.0001); 0.9, 1, 0 for switchers from IFNB or GA to natalizumab (P = 0.0001). CONCLUSIONS: In patients with RRMS who have a poor response, switch to another DMD may reduce the clinical activity of the disease.

Replication of top markers of a genome-wide association study in multiple sclerosis in Spain.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with presumed autoimmune origin, triggered by genetic and environmental risk factors. A recent genome-wide association study conducted on MS identified new biallelic markers outside the HLA (human leucocyte antigen) region involved in disease susceptibility: rs1109670 (DDEF2); rs1458175 (PDZRN4); rs1529316 and rs2049306 (CSMD1); rs16914086 (TBC1D2); rs1755289 (SH3GL2); rs1841770 (ZIC1); rs651477 (EN1); rs7607490 (TRIB2); rs397020 (C20orf46); rs908821 (SLC25A36); rs7672826 (MGC45800) and rs9523762 (GPC5). We aimed at replicating these top association signals in a Spanish cohort of 2863 MS patients and 2930 sex- and age-matched controls. Only rs9523762 mapping in the GPC5 gene was significantly associated (G allele, P=1.6 × 10(-5); odds ratio (95% confidence interval)=1.23 (1.12-1.36)), supporting a role for this proteoglycan in MS predisposition. The independent replication of association signals to validate data generated by genome-wide association scans is a first step in the effort to improve patient care.

Interferon regulatory factor 5 gene variants and pharmacological and clinical outcome of Interferonß therapy in multiple sclerosis.

Interferon-ß (IFNß) therapy is effective in approximately half of the patients with relapsing-remitting multiple sclerosis (RRMS). Clinical non-responders were characterized by an increased expression of IFN response genes before the start of therapy, and a lack of a pharmacologically induced increase in IFN response gene activity. Because Interferon Regulatory Factor 5 (IRF5) is a master regulator of IFN-activity, we carried out a candidate gene study of IRF5 gene variants in relation to the pharmacological and clinical response upon IFNß treatment. We found that patients with the IRF5 rs2004640-TT and rs47281420-AA genotype exerted a poor pharmacological response to IFNß compared with patients carrying the respective G-alleles (P=0.0006 and P=0.0023, respectively). Moreover, patients with the rs2004640-TT genotype developed more magnetic resonance imaging (MRI)-based T2 lesions during IFNß treatment (P=0.003). Accordingly, an association between MRI-based non-responder status and rs2004640-TT genotype was observed (P=0.010). For the rs4728142-AA genotype a trend of an association with more T2 lesions during IFNß treatment and MRI-based non-responder status was observed (P=0.103 and P=0.154, respectively). The clinical relevance of the rs2004640-TT genotype was validated in an independent cohort wherein a shorter time to first relapse was found (P=0.037). These findings suggest a role for IRF5 gene variation in the pharmacological and clinical outcome of IFNß therapy that might have relevance as biomarker to predict the response to IFNß in multiple sclerosis.

Natural killer cell phenotype and clinical response to interferon-beta therapy in multiple sclerosis.

CD56(bright) NK cells, which may play a role in immunoregulation, are expanded in multiple sclerosis (MS) patients treated with immunomodulatory therapies such as daclizumab and interferon-beta (IFNß). Yet, whether this NK cell subset is directly involved in the therapeutic effect is unknown. As NK receptor (NKR) expression by subsets of NK cells and CD8+ T lymphocytes is related to MS clinical course, we addressed whether CD56(bright) NK cells and NKR in IFNß-treated MS patients differ according to the clinical response. IFNß was associated to lower LILRB1+ and KIR+NK cells, and higher NKG2A+NK cell proportions, an immunophenotypic pattern mainly found in responders. After IFNß treatment, a CD56(bright) NK cell expansion was significantly related to a positive clinical response. Our results reveal that IFNß may promote in responders changes in the NK cell immunophenotype, corresponding to the profile found at early maturation stages of this lymphocyte lineage.

Role of tumour necrosis factor (TNF)-α and TNFRSF1A R92Q mutation in the pathogenesis of TNF receptor-associated periodic syndrome and multiple sclerosis.

It has long been known that tumour necrosis factor (TNF)/TNFRSF1A signalling is involved in the pathophysiology of multiple sclerosis (MS). Different genetic and clinical findings over the last few years have generated renewed interest in this relationship. This paper provides an update on these recent findings. Genome-wide association studies have identified the R92Q mutation in the TNFRSF1A gene as a genetic risk factor for MS (odds ratio 1·6). This allele, which is also common in the general population and in other inflammatory conditions, therefore only implies a modest risk for MS and provides yet another piece of the puzzle that defines the multiple genetic risk factors for this disease. TNFRSF1A mutations have been associated with an autoinflammatory disease known as TNF receptor-associated periodic syndrome (TRAPS). Clinical observations have identified a group of MS patients carrying the R92Q mutation who have additional TRAPS symptoms. Hypothetically, the co-existence of MS and TRAPS or a co-morbidity relationship between the two could be mediated by this mutation. The TNFRSF1A R92Q mutation behaves as a genetic risk factor for MS and other inflammatory diseases, including TRAPS. Nevertheless, this mutation does not appear to be a severity marker of the disease, neither modifying the clinical progression of MS nor its therapeutic response. An alteration in TNF/TNFRS1A signalling may increase proinflammatory signals; the final clinical phenotype may possibly be determined by other genetic or environmental modifying factors that have not yet been identified.

13th Post-ECTRIMS Meeting: review of the new developments presented at the 2020 ECTRIMS Congress (I). / XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (I).

INTRODUCTION: For more than a decade, following the ECTRIMS Congress, the Post-ECTRIMS Meeting has been held in Spain, where neurologists with expertise in multiple sclerosis (MS) from all over the country meet to review the most relevant latest developments presented at the ECTRIMS congress (on this occasion held together with ACTRIMS). AIM: This article, published in two parts, summarises the presentations that took place at the Post-ECTRIMS Meeting, held online on 16 and 17 October 2020. DEVELOPMENT: This first part includes the latest results regarding the impact of the environment and lifestyle on risk of MS and its clinical course, and the role of epigenetics and genetic factors on these processes. Findings from preclinical and clinical research on the lymphocyte subtypes identified and the involvement of lymphoid follicles and meningeal involvement in the disease are discussed. Changes in brain structure are addressed at the microscopic and macroscopic levels, including results from high-resolution imaging techniques. The latest advances on biomarkers for the diagnosis and prognosis of MS, and on the involvement of the microbiome in these patients are also reported. Finally, results from patient registries on the impact of COVID-19 in MS patients are outlined. CONCLUSIONS: There have been new data on MS risk factors, the impact of MS at the cellular and structural level, the role of the microbiome in the disease, biomarkers, and the relationship between COVID-19 and MS.

TITLE: XIII Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (I).Introducción. Desde hace más de una década, tras el congreso ECTRIMS, se celebra en España la reunión Post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) de toda España se reúnen para revisar las principales novedades presentadas en el ECTRIMS (en esta ocasión, celebrado junto con el ACTRIMS). Objetivo. En el presente artículo, publicado en dos partes, se resumen las ponencias que tuvieron lugar en la reunión Post-ECTRIMS, celebrada los días 16 y 17 de octubre de 2020 de forma virtual. Desarrollo. En esta primera parte se incluyen los últimos resultados acerca del impacto del ambiente y el estilo de vida sobre el riesgo de EM y su curso clínico, y el papel de la epigenética y los factores genéticos sobre estos procesos. Se discuten los hallazgos en investigación preclínica y clínica sobre los subtipos de linfocitos identificados, y la implicación de los folículos linfoides y la afectación meníngea en la enfermedad. Los cambios en la estructura cerebral se abordan a nivel microscópico y macroscópico, incluyendo resultados de técnicas de imagen de alta resolución. También se presentan los últimos avances sobre biomarcadores para el diagnóstico y el pronóstico de la EM, y sobre la afectación del microbioma en estos pacientes. Por último, se esbozan los resultados de registros de pacientes sobre el impacto de la COVID-19 en los pacientes con EM. Conclusiones. Ha habido nuevos datos sobre factores de riesgo de la EM, impacto de la EM a nivel celular y estructural, papel del microbioma en la enfermedad, biomarcadores y la relación entre COVID-19 y EM.