TY - JOUR
T1 - Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis
AU - Engdahl, Elin
AU - Gustafsson, Rasmus
AU - Huang, Jesse
AU - Biström, Martin
AU - Lima Bomfim, Izaura
AU - Stridh, Pernilla
AU - Khademi, Mohsen
AU - Brenner, Nicole
AU - Butt, Julia
AU - Michel, Angelika
AU - Jons, Daniel
AU - Hortlund, Maria
AU - Alonso-Magdalena, Lucia
AU - Hedström, Anna Karin
AU - Flamand, Louis
AU - Ihira, Masaru
AU - Yoshikawa, Tetsushi
AU - Andersen, Oluf
AU - Hillert, Jan
AU - Alfredsson, Lars
AU - Waterboer, Tim
AU - Sundström, Peter
AU - Olsson, Tomas
AU - Kockum, Ingrid
AU - Fogdell-Hahn, Anna
N1 - Publisher Copyright:
© 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.
PY - 2019/11/26
Y1 - 2019/11/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85076683059&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85076683059&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2019.02715
DO - 10.3389/fimmu.2019.02715
M3 - Article
C2 - 32038605
AN - SCOPUS:85076683059
SN - 1664-3224
VL - 10
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 2715
ER -
