SARS-CoV-2 Infection in Multiple Sclerosis

To understand COVID-19 characteristics in people with multiple sclerosis (MS) and identify high-risk individuals due to their immunocompromised state resulting from the use of disease-modifying treatments. Retrospective and multicenter registry in patients with MS with suspected or confirmed COVID-19 diagnosis and available disease course (mild = ambulatory; severe = hospitalization; and critical = intensive care unit/death). Cases were analyzed for associations between MS characteristics and COVID-19 course and for identifying risk factors for a fatal outcome. Of the 326 patients analyzed, 120 were cases confirmed by real-time PCR, 34 by a serologic test, and 205 were suspected. Sixty-nine patients (21.3%) developed severe infection, 10 (3%) critical, and 7 (2.1%) died. Ambulatory patients were higher in relapsing MS forms, treated with injectables and oral first-line agents, whereas more severe cases were observed in patients on pulsed immunosuppressors and critical cases among patients with no therapy. Severe and critical infections were more likely to affect older males with comorbidities, with progressive MS forms, a longer disease course, and higher disability. Fifteen of 33 patients treated with rituximab were hospitalized. Four deceased patients have progressive MS, 5 were not receiving MS therapy, and 2 were treated (natalizumab and rituximab). Multivariate analysis showed age (OR 1.09, 95% CI, 1.04-1.17) as the only independent risk factor for a fatal outcome. This study has not demonstrated the presumed critical role of MS therapy in the course of COVID-19 but evidenced that people with MS with advanced age and disease, in progressive course, and those who are more disabled have a higher probability of severe and even fatal diseas

NQO1 gene rs1800566 variant is not associated with risk for multiple sclerosis

Abstract Background A possible role of oxidative stress in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis has been suggested. The detoxification enzyme NAD(P)H dehydrogenase, quinone 1 (NQO1) has been found up-regulated in MS lesions. A previous report described an association between the SNP rs1800566 in the NQO1 gene and the risk for MS in the Greek population. The aim of this study was to replicate a possible influence of the. SNP rs1800566 in the NQO1 gene in the risk for MS in the Spanish Caucasian population. Methods We analyzed allelic and genotypic frequency of NQO1 rs1800566 in 290 patients with MS and 310 healthy controls, using TaqMan Assays. Results NQO1 rs1800566 allelic and genotypic frequencies did not differ significantly between MS patients and controls, and were unrelated with age of onset of MS, gender, and clinical type of MS. Conclusions Our results indicate that NQO1 rs1800566 does not have an effect on MS disease risk.This work was supported in part by Grants PI12/00241, PI12/00324 and RETICS RD12/0013/0002 from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain, and GR10068 from Junta de Extremadura, Spain. Financed in part with FEDER funds from the European Union.Peer Reviewe

LINGO1 rs9652490 and rs11856808 polymorphisms are not associated with risk for multiple sclerosis

Background: Some recent experimental data suggest a possible role of LINGO-1 in the pathogenesis of multiple sclerosis (MS). In an attempt to identify genetic biomarkers related to MS susceptibility, we genotyped two common SNPs in the LINGO1 gene which have been associated to other neurological conditions, in patients with MS and in healthy subjects. These SNPs are linked to several SNPs within the LINGO1 gene, especially in individuals of Oriental or Caucasian descent.Methods: We analyzed the allelic and genotype frequency of two LINGO1 variants (rs9652490 and rs11856808) in 293 patients with MS and 318 healthy controls, using KASPar assays.Results: LINGO1 rs9652490 and rs11856808 allelic and genotype frequencies did not differ significantly between MS patients and controls. The minor allele frequencies for rs9652490 were 0.171 (95% CI = 0.140-0.201) and 0.167 (95% CI = 0.138-0.196 for cases and controls respectively (p = 0.853). For rs11856808 the minor allele frequencies were 0.317 (95% CI = 0.280-0.355) and 0.310 (95% CI = 0.274-0.346) for cases and controls, respectively (p = 0.773). Allele and genotype frequencies were unrelated with the age of onset of MS, gender, and clinical course of MS. In addition, haplotype analyses did not reveal any putative risk related to haplotypes.Conclusions: These results suggest that LINGO1 rs9652490 and rs11856808 polymorphisms are not related with risk for MS. This study adds to other published evidence indicating that, to date, the LINGO1 SNPs studied here could be useful risk biomarkers of developing essential tremor, but not other movement disorders. © 2013 García-Martín et al.; licensee BioMed Central Ltd.Instituto de Salud Carlos III PS09/00943, PS09/00469, PI12/00241, PI12/00324 and RETICS RD12/0013/0002 from Fondo de Investigación Sanitaria; Spanish Ministry of Science and Innovation (SAF2006-10126 and SAF2010-22329-C02-01); Junta de Extremadura (GR10068); European Union (FEDER)Peer Reviewe

Predicting conversion to multiple sclerosis by assessing cognitive impairment in radiologically isolated syndrome

Up to a third of patients with radiologically isolated syndrome (RIS) exhibit lower-than-expected cognitive performances in neuropsychological evaluations, but the relationship between cognitive impairment (CI) and quantitative magnetic resonance (MRI) measures has not been stablished. Furthermore, the prognostic role of CI in RIS for conversion to MS is currently unknown. We assessed 17 patients with RIS and 17 matched healthy controls (HC) with a neurophychological battery and a 3T MRI. Six patients (35,3%) fulfilled our criterion for CI (scores 2 SDs below the mean of HC in at least two cognitive tests) (ci-RIS). The ci-RIS subgroup showed lower values of normalized brain and gray matter volumes when compared to HC. After a median follow-up time of 4.5 years, the ci-RIS subgroup presented a higher conversion rate to MS, suggesting that CI might be an independent risk factor for conversion to MS

MAPT gene rs1052553 variant is not associated with the risk for multiple sclerosis

Background/Objectives: Some experimental data suggest a possible role of tau protein in the pathogenesis of multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis. The aim of this study was to investigate a possible influence of the SNP rs1052553 in the MAPT gene in the risk for relapsing bout onset (relapsing-remitting and secondary progressive) MS. Methods: We analyzed the allelic and genotype frequency of MAPT rs1052553, which has been associated with some neurodegenerative diseases, in 259 patients with relapsing bout onset MS and 291 healthy controls, using TaqMan Assays. Results: MAPT rs1052553 allelic and genotype frequencies did not differ significantly between relapsing bout onset MS patients and controls, and were unrelated with the age of onset of MS or gender. Conclusions: These results suggest that MAPT rs1052553 polymorphism is not related with the risk for relapsing bout onset MS. © 2013 American Society for Histocompatibility and Immunogenetics.Junta de Extremadura, Spain (GR10068); European Union (FEDER)Peer Reviewe

Heme oxygenase-1 and 2 common genetic variants and risk for multiple sclerosis

Varios neurotransmisores, neuropatológicos, y los datos experimentales sugieren un posible papel del estrés oxidativo en la etiopatogenia de la esclerosis múltiple (MS). Hemo-oxygenases(HMOX) son un importante mecanismo de defensa contra el estrés oxidativo y HMOX1 está sobre expresado en el cerebro y la médula espinal de los pacientes de esclerosis múltiple y en la encefalomielitis autoinmune experimental (EAE). Hemos analizado si los polimorfismos comunes que afectan a la HMOX1 y HMOX2 genes están relacionados con el riesgo de desarrollar MS. Se analizó la distribución de genotipos y frecuencias alélicas de los HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363 y rs1051308 HMOX2 SNPs, así como la presencia de variaciones de número de copia (CNVs) de estos genes en 292 sujetos ms y 533 controles sanos, utilizando ensayos TaqMan. Las frecuencias de HMOX genotipo AA1051308rs2 y Rs2 HMOX1051308A y HMOX1 rs2071746Un alelos MS fueron superiores en los pacientes que en los controles, aunque solamente del SNP rs1051308 HMOX2 en el hombre seguía siendo tan significativas después de la corrección para comparaciones múltiples. Ninguno de los polimorfismos estudiados se relaciona con la edad al inicio de la enfermedad o con el fenotipo de MS. El presente estudio sugiere una débil asociación entre el polimorfismo rs1051308 HMOX2 y el riesgo de desarrollar MS en español los hombres caucásicos y una tendencia hacia una asociación entre el HMOX1 rs2071746A y MS riesgo.Several neurochemical, neuropathological, and experimental data suggest a possible role of oxidative stress in the ethiopathogenesis of multiple sclerosis (MS). Heme-oxygenases (HMOX) are an important defensive mechanism against oxidative stress, and HMOX1 is overexpressed in the brain and spinal cord of MS patients and in experimental autoimmune encephalomyelitis(EAE). We analyzed whether common polymorphisms affecting the HMOX1 and HMOX2 genes are related with the risk to develop MS. We analyzed the distribution of genotypes and allelic frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363, and HMOX2 rs1051308 SNPs, as well as the presence of Copy number variations(CNVs) of these genes in 292 subjects MS and 533 healthy controls, using TaqMan assays. The frequencies of HMOX2 rs1051308AA genotype and HMOX2 rs1051308A and HMOX1 rs2071746A alleles were higher in MS patients than in controls, although only that of the SNP HMOX2 rs1051308 in men remained as significant after correction for multiple comparisons. None of the studied polymorphisms was related to the age at disease onset or with the MS phenotype. The present study suggests a weak association between HMOX2 rs1051308 polymorphism and the risk to develop MS in Spanish Caucasian men and a trend towards association between the HMOX1 rs2071746A and MS risk.Trabajo patrocinado por: Instituto de Salud Carlos III. Fondo de Investigación Sanitaria. Becas PI12/00241, PI12/00324 y RETICS RD12/0013/0002 Junta de Extremadura y Fondos FEDER. Ayuda GR15026peerReviewednotPeerReviewe

Case-control studies on <i>VDR</i> rs731236 (Taq1) and risk for MS (NA = data not available).

<p>Case-control studies on <i>VDR</i> rs731236 (Taq1) and risk for MS (NA =  data not available).</p

Gene-gene interaction between the HLA-DRB1*1501 tagging SNP (rs3135388), and the VDR gene polymorphisms in patients with MS.

<p>NPV negative predictive value.</p><p>Combinations for all genotypes were analyzed in 302 MS patients and 309 controls. The frequencies shown correspond to the frequencies of a particular combination of VDR genotype within every rs3135388 (HLADRB1*1501) genotype category.</p

<i>HLADRB1*1501</i> (rs3135388) genotypes and allelic variants in patients with MS, and relation with the evolutive type of MS.

<p>The values in each cell represent: number (percentage; 95% confidence intervals).</p