Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis
Copyright © 2019 Engdahl, Gustafsson, Huang, Biström, Lima Bomfim, Stridh, Khademi, Brenner, Butt, Michel, Jons, Hortlund, Alonso-Magdalena, Hedström, Flamand, Ihira, Yoshikawa, Andersen, Hillert, Alfredsson, Waterboer, Sundström, Olsson, Kockum and Fogdell-Hahn..
Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology has remained controversial mainly due to the lack of serological methods that can distinguish the two viruses. A novel multiplex serological assay measuring IgG reactivity against the immediate-early protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS cohort (8,742 persons with MS and 7,215 matched controls), and a pre-MS cohort (478 individuals and 476 matched controls) to investigate this further. The IgG response against IE1A was positively associated with MS (OR = 1.55, p = 9 × 10-22), and increased risk of future MS (OR = 2.22, p = 2 × 10-5). An interaction was observed between IE1A and Epstein-Barr virus (EBV) antibody responses for MS risk (attributable proportion = 0.24, p = 6 × 10-6). In contrast, the IgG response against IE1B was negatively associated with MS (OR = 0.74, p = 6 × 10-11). The association did not differ between MS subtypes or vary with severity of disease. The genetic control of HHV-6A/B antibody responses were located to the Human Leukocyte Antigen (HLA) region and the strongest association for IE1A was the DRB1*13:01-DQA1*01:03-DQB1*06:03 haplotype while the main association for IE1B was DRB1*13:02-DQA1*01:02-DQB1*06:04. In conclusion a role for HHV-6A in MS etiology is supported by an increased serological response against HHV-6A IE1 protein, an interaction with EBV, and an association to HLA genes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Frontiers in immunology - 10(2019) vom: 07., Seite 2715 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Engdahl, Elin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.11.2020 Date Revised 23.04.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.3389/fimmu.2019.02715 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis |
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| 520 | |a Copyright © 2019 Engdahl, Gustafsson, Huang, Biström, Lima Bomfim, Stridh, Khademi, Brenner, Butt, Michel, Jons, Hortlund, Alonso-Magdalena, Hedström, Flamand, Ihira, Yoshikawa, Andersen, Hillert, Alfredsson, Waterboer, Sundström, Olsson, Kockum and Fogdell-Hahn. | ||
| 520 | |a Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology has remained controversial mainly due to the lack of serological methods that can distinguish the two viruses. A novel multiplex serological assay measuring IgG reactivity against the immediate-early protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS cohort (8,742 persons with MS and 7,215 matched controls), and a pre-MS cohort (478 individuals and 476 matched controls) to investigate this further. The IgG response against IE1A was positively associated with MS (OR = 1.55, p = 9 × 10-22), and increased risk of future MS (OR = 2.22, p = 2 × 10-5). An interaction was observed between IE1A and Epstein-Barr virus (EBV) antibody responses for MS risk (attributable proportion = 0.24, p = 6 × 10-6). In contrast, the IgG response against IE1B was negatively associated with MS (OR = 0.74, p = 6 × 10-11). The association did not differ between MS subtypes or vary with severity of disease. The genetic control of HHV-6A/B antibody responses were located to the Human Leukocyte Antigen (HLA) region and the strongest association for IE1A was the DRB1*13:01-DQA1*01:03-DQB1*06:03 haplotype while the main association for IE1B was DRB1*13:02-DQA1*01:02-DQB1*06:04. In conclusion a role for HHV-6A in MS etiology is supported by an increased serological response against HHV-6A IE1 protein, an interaction with EBV, and an association to HLA genes | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Gustafsson, Rasmus |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jesse |e verfasserin |4 aut | |
| 700 | 1 | |a Biström, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Lima Bomfim, Izaura |e verfasserin |4 aut | |
| 700 | 1 | |a Stridh, Pernilla |e verfasserin |4 aut | |
| 700 | 1 | |a Khademi, Mohsen |e verfasserin |4 aut | |
| 700 | 1 | |a Brenner, Nicole |e verfasserin |4 aut | |
| 700 | 1 | |a Butt, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Michel, Angelika |e verfasserin |4 aut | |
| 700 | 1 | |a Jons, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Hortlund, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Alonso-Magdalena, Lucia |e verfasserin |4 aut | |
| 700 | 1 | |a Hedström, Anna Karin |e verfasserin |4 aut | |
| 700 | 1 | |a Flamand, Louis |e verfasserin |4 aut | |
| 700 | 1 | |a Ihira, Masaru |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshikawa, Tetsushi |e verfasserin |4 aut | |
| 700 | 1 | |a Andersen, Oluf |e verfasserin |4 aut | |
| 700 | 1 | |a Hillert, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Alfredsson, Lars |e verfasserin |4 aut | |
| 700 | 1 | |a Waterboer, Tim |e verfasserin |4 aut | |
| 700 | 1 | |a Sundström, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Olsson, Tomas |e verfasserin |4 aut | |
| 700 | 1 | |a Kockum, Ingrid |e verfasserin |4 aut | |
| 700 | 1 | |a Fogdell-Hahn, Anna |e verfasserin |4 aut | |
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