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Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis

Engdahl, Elin ; Gustafsson, Rasmus ; Huang, Jesse ; Biström, Martin ; Lima Bomfim, Izaura ; Stridh, Pernilla ; Khademi, Mohsen ; Brenner, Nicole ; Butt, Julia and Michel, Angelika , et al. (2019) In Frontiers in Immunology 10.
Abstract

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)... (More)

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.

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publication status
published
subject
keywords
association, Epstein-Barr virus, human herpesvirus 6A, human herpesvirus 6B, human leukocyte antigen, multiple sclerosis, risk, serology
in
Frontiers in Immunology
volume
10
article number
2715
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85076683059
  • pmid:32038605
ISSN
1664-3224
DOI
10.3389/fimmu.2019.02715
language
English
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no
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bc006f50-abef-42c4-ab5b-9aab093223ee
date added to LUP
2020-01-13 12:31:37
date last changed
2020-07-12 06:05:26
@article{bc006f50-abef-42c4-ab5b-9aab093223ee,
  abstract     = {<p>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<sup>−22</sup>), and increased risk of future MS (OR = 2.22, p = 2 × 10<sup>−5</sup>). An interaction was observed between IE1A and Epstein-Barr virus (EBV) antibody responses for MS risk (attributable proportion = 0.24, p = 6 × 10<sup>−6</sup>). In contrast, the IgG response against IE1B was negatively associated with MS (OR = 0.74, p = 6 × 10<sup>−11</sup>). 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<sup>*</sup>13:01-DQA1<sup>*</sup>01:03-DQB1<sup>*</sup>06:03 haplotype while the main association for IE1B was DRB1<sup>*</sup>13:02-DQA1<sup>*</sup>01:02-DQB1<sup>*</sup>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.</p>},
  author       = {Engdahl, Elin and Gustafsson, Rasmus and Huang, Jesse and Biström, Martin and Lima Bomfim, Izaura and Stridh, Pernilla and Khademi, Mohsen and Brenner, Nicole and Butt, Julia and Michel, Angelika and Jons, Daniel and Hortlund, Maria and Alonso-Magdalena, Lucia and Hedström, Anna Karin and Flamand, Louis and Ihira, Masaru and Yoshikawa, Tetsushi and Andersen, Oluf and Hillert, Jan and Alfredsson, Lars and Waterboer, Tim and Sundström, Peter and Olsson, Tomas and Kockum, Ingrid and Fogdell-Hahn, Anna},
  issn         = {1664-3224},
  language     = {eng},
  month        = {11},
  publisher    = {Frontiers Media S. A.},
  series       = {Frontiers in Immunology},
  title        = {Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis},
  url          = {http://dx.doi.org/10.3389/fimmu.2019.02715},
  doi          = {10.3389/fimmu.2019.02715},
  volume       = {10},
  year         = {2019},
}