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Impact of multiple sclerosis risk loci in postinfectious neurological syndromes.
Mult Scler Relat Disord. 2020 Jun 24; 44:102326.MS

Abstract

BACKGROUND

The genetic component of multiple sclerosis (MS) is now set to 200 autosomal common variants. However, it is unclear how genetic knowledge be clinically used in the differential diagnosis between MS and other inflammatory conditions like adult-onset postinfectious neurological syndromes (PINS). The aim of this study was to investigate whether PINS and MS have a shared genetic background using an updated polygenic risk scores.

METHODS

Eighty-eight PINS patients have been consecutively recruited between 1996 and 2016 at Mondino Foundation of Pavia, diagnosed according to clinical, MRI and CSF findings and followed-up for several years. Patients were typed using Illumina array, and genotypes imputed using the 1000 Genomes Project reference panel. A weighted genetic risk score (wGRS) has been calculated based on autosomal MS risk loci derived from large-scale studies, and an HLA genetic burden (HLAGB) was also calculated on loci associated to MS.

RESULTS

PINS occurred as an episode of myelitis in 44% of patients, encephalomyelitis in 44%, and encephalitis in remaining cases, with an involvement of peripheral nervous system in 41% of patients. Mean age of onset was 50.1 years, and female:male ratio was 1.4. Patients were followed-up for a mean of 7.2 years, and at last visit 55% had a low disability grade (mRS 0-1). Disease was monophasic in 67% of patients, relapsing in 18% and chronic-progressive in 15%. The wGRS of PINS cases was comparable to 370 healthy controls, while significantly lower compared to 907 bout-onset MS (BOMS) cases (wGRS= 20.9 vs 21.2; p<0.0001). The difference was even larger for PINS with peripheral nervous system involvement (wGRS=20.6) vs BOMS.

CONCLUSION

The distinction between MS and PINS is not easy to make in clinical practice. However, our study shows that the new set of MS risk alleles does not confer increased susceptibility to PINS. These data support the importance to discriminate these cases from MS with pathophysiological and therapeutic implications.

Authors+Show Affiliations

Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Via Francesco Sforza 35, 20122 Milan, Italy; Neurology Unit and MS Centre, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy. Electronic address: filippo.martinelli@unimi.it.Department of Brain and Behavioral Sciences, University of Pavia, via Forlanini 6, 27100 Pavia, Italy; Fondazione Istituto Neurologico Nazionale IRCCS Mondino, via Mondino 2, 27100 Pavia, Italy.Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 48 - 20132 Milan, Italy.Department of Brain and Behavioral Sciences, University of Pavia, via Forlanini 6, 27100 Pavia, Italy; Fondazione Istituto Neurologico Nazionale IRCCS Mondino, via Mondino 2, 27100 Pavia, Italy.Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 48 - 20132 Milan, Italy.Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 48 - 20132 Milan, Italy; Neurology Unit, San Raffaele Scientific Institute, Via Olgettina 48 - 20132 Milan, Italy.Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 48 - 20132 Milan, Italy.Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 48 - 20132 Milan, Italy.Neurology Unit, San Raffaele Scientific Institute, Via Olgettina 48 - 20132 Milan, Italy.Department of Surgical, Pediatric, and Diagnostic Sciences, University of Pavia, Viale Brambilla 74, 27100 Pavia, Italy; UOC Anestesia e Rianimazione, IRCCS Policlinico San Matteo, Viale Camillo Golgi 19, 27100 Pavia, Italy.Department of Brain and Behavioral Sciences, University of Pavia, via Forlanini 6, 27100 Pavia, Italy; Fondazione Istituto Neurologico Nazionale IRCCS Mondino, via Mondino 2, 27100 Pavia, Italy.Department of Brain and Behavioral Sciences, University of Pavia, via Forlanini 6, 27100 Pavia, Italy; Fondazione Istituto Neurologico Nazionale IRCCS Mondino, via Mondino 2, 27100 Pavia, Italy.Neurology Unit, San Raffaele Scientific Institute, Via Olgettina 48 - 20132 Milan, Italy; Vita-Salute San Raffaele University, Via Olgettina 48 - 20132 Milan, Italy; Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina 48 - 20132 Milan, Italy; Neurophisiology Unit, IRCCS San Raffaele Scientific Institute, San Raffaele Scientific Institute, Via Olgettina 48 - 20132 Milan, Italy.Department of Brain and Behavioral Sciences, University of Pavia, via Forlanini 6, 27100 Pavia, Italy; Fondazione Istituto Neurologico Nazionale IRCCS Mondino, via Mondino 2, 27100 Pavia, Italy.Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 48 - 20132 Milan, Italy; Neurology Unit, San Raffaele Scientific Institute, Via Olgettina 48 - 20132 Milan, Italy.Laboratory of Human Genetics of Neurological Disorders, Institute of Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 48 - 20132 Milan, Italy.Fondazione Istituto Neurologico Nazionale IRCCS Mondino, via Mondino 2, 27100 Pavia, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32615529

Citation

Martinelli-Boneschi, Filippo, et al. "Impact of Multiple Sclerosis Risk Loci in Postinfectious Neurological Syndromes." Multiple Sclerosis and Related Disorders, vol. 44, 2020, p. 102326.
Martinelli-Boneschi F, Currò R, Santoro S, et al. Impact of multiple sclerosis risk loci in postinfectious neurological syndromes. Mult Scler Relat Disord. 2020;44:102326.
Martinelli-Boneschi, F., Currò, R., Santoro, S., Berzero, G., Sorosina, M., Ferrè, L., Mascia, E., Peroni, S., Comi, G., Gugliemi, A., Vegezzi, E., Callegari, I., Filippi, M., Cortese, A., Esposito, F., Clarelli, F., & Marchioni, E. (2020). Impact of multiple sclerosis risk loci in postinfectious neurological syndromes. Multiple Sclerosis and Related Disorders, 44, 102326. https://doi.org/10.1016/j.msard.2020.102326
Martinelli-Boneschi F, et al. Impact of Multiple Sclerosis Risk Loci in Postinfectious Neurological Syndromes. Mult Scler Relat Disord. 2020 Jun 24;44:102326. PubMed PMID: 32615529.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of multiple sclerosis risk loci in postinfectious neurological syndromes. AU - Martinelli-Boneschi,Filippo, AU - Currò,Riccardo, AU - Santoro,Silvia, AU - Berzero,Giulia, AU - Sorosina,Melissa, AU - Ferrè,Laura, AU - Mascia,Elisabetta, AU - Peroni,Silvia, AU - Comi,Giancarlo, AU - Gugliemi,Angelo, AU - Vegezzi,Elisa, AU - Callegari,Ilaria, AU - Filippi,Massimo, AU - Cortese,Andrea, AU - Esposito,Federica, AU - Clarelli,Ferdinando, AU - Marchioni,Enrico, Y1 - 2020/06/24/ PY - 2020/03/27/received PY - 2020/05/22/revised PY - 2020/06/21/accepted PY - 2020/7/3/pubmed PY - 2020/7/3/medline PY - 2020/7/3/entrez KW - Acquired demyelinating disease KW - Genetics KW - Multiple sclerosis KW - Postinfectious neurological syndrome KW - Weighted genetic risk score SP - 102326 EP - 102326 JF - Multiple sclerosis and related disorders JO - Mult Scler Relat Disord VL - 44 N2 - BACKGROUND: The genetic component of multiple sclerosis (MS) is now set to 200 autosomal common variants. However, it is unclear how genetic knowledge be clinically used in the differential diagnosis between MS and other inflammatory conditions like adult-onset postinfectious neurological syndromes (PINS). The aim of this study was to investigate whether PINS and MS have a shared genetic background using an updated polygenic risk scores. METHODS: Eighty-eight PINS patients have been consecutively recruited between 1996 and 2016 at Mondino Foundation of Pavia, diagnosed according to clinical, MRI and CSF findings and followed-up for several years. Patients were typed using Illumina array, and genotypes imputed using the 1000 Genomes Project reference panel. A weighted genetic risk score (wGRS) has been calculated based on autosomal MS risk loci derived from large-scale studies, and an HLA genetic burden (HLAGB) was also calculated on loci associated to MS. RESULTS: PINS occurred as an episode of myelitis in 44% of patients, encephalomyelitis in 44%, and encephalitis in remaining cases, with an involvement of peripheral nervous system in 41% of patients. Mean age of onset was 50.1 years, and female:male ratio was 1.4. Patients were followed-up for a mean of 7.2 years, and at last visit 55% had a low disability grade (mRS 0-1). Disease was monophasic in 67% of patients, relapsing in 18% and chronic-progressive in 15%. The wGRS of PINS cases was comparable to 370 healthy controls, while significantly lower compared to 907 bout-onset MS (BOMS) cases (wGRS= 20.9 vs 21.2; p<0.0001). The difference was even larger for PINS with peripheral nervous system involvement (wGRS=20.6) vs BOMS. CONCLUSION: The distinction between MS and PINS is not easy to make in clinical practice. However, our study shows that the new set of MS risk alleles does not confer increased susceptibility to PINS. These data support the importance to discriminate these cases from MS with pathophysiological and therapeutic implications. SN - 2211-0356 UR - https://www.unboundmedicine.com/medline/citation/32615529/Impact_of_multiple_sclerosis_risk_loci_in_postinfectious_neurological_syndromes L2 - https://linkinghub.elsevier.com/retrieve/pii/S2211-0348(20)30402-8 DB - PRIME DP - Unbound Medicine ER -
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